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Cited by 292Balance, Gait, and Falls PreventionAging and Gerontology ResearchFrailty in Older Adults

Successful aging: Advancing the science of physical independence in older adults

Open access
Anton, Stephen D., Woods, Adam J., Ashizawa, Tetso, Barb, Diana, Buford, Thomas W., Carter, Christy S., Clark, David J., Cohen, Ronald A. +27 more·2015·Ageing Research Reviews
DOI 10.1016/j.arr.2015.09.005PMC PMC4661112
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Abstract

The concept of ‘Successful Aging’ has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. The domain in which consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that “Successful Aging” lacks a consensus definition, but the physical functioning domain has the strongest consensus markers, especially walking speed and the Short Physical Performance Battery (SPPB). It overviews health conditions, behavioral factors, biological mechanisms, and promising interventions tied to maintaining physical independence in older adults.

Key findings

  • Walking speed and SPPB are proposed as surrogate markers of successful aging within the physical domain: slow walking speed (<1 m/sec high risk; <0.8 m/sec very high risk) predicts functional decline, major health outcomes, and mortality; SPPB scores range 0–12, and meaningful changes are Δ > 0.05 m/sec for walking speed and Δ > 0.5 points for SPPB.
  • Functional decline is linked to cognitive decline, obesity (33% of American older adults age >60), sarcopenia (1–2% muscle loss per year after age 50), dynapenia (grip strength <26 kg in men and <16 kg in women predicts mobility disability), chronic pain (up to 70% in community settings and 80% in nursing homes), poor sleep, environmental stress, and depression.
  • Biological mechanisms implicated include mitochondrial dysfunction and dynamics, autophagy, mtDNA mutations, chronic inflammation (CRP, TNF-α, IL-6), hormonal changes, and cerebral/peripheral neurodegeneration.
  • Exercise is the only intervention consistently demonstrated to attenuate functional decline; other promising approaches include dietary restriction in obese older adults, smart/connected technologies, cognitive training, exergaming, non-invasive brain stimulation, pharmaceuticals (e.g., ACE inhibitors as adjuncts to exercise), nutraceuticals (e.g., resveratrol), and hormonal interventions (e.g., oxytocin), though no FDA-approved medications exist for functional decline.

Methods

  • Narrative review/overview; the paper states no systematic review protocol, search strategy, inclusion criteria, or meta-analysis.
  • Data or sample: Not stated in the paper; it synthesizes existing studies rather than presenting primary data.
  • Main analysis: narrative synthesis across health conditions, behavioral/social factors, biological mechanisms, interventions, and statistical considerations, with conceptual figures and a table summarizing lifestyle intervention trials.

Limitations

  • The paper states that the lack of a consensus definition and standardized metrics for successful aging limits cross-study comparisons and advances; mechanisms of age-related functional decline remain largely undefined; there are no FDA-approved medications for functional decline; few trials support dietary restriction alone; many cognitive training effects are limited to trained tasks; exercise benefits are variable and not observed in all individuals; and it is unknown whether reducing inflammatory markers per se improves mobility.
  • Evident from the text: as a narrative review, it lacks systematic search, quality appraisal, and quantitative synthesis, and its conclusions rely on cited literature and expert synthesis rather than primary data testing the proposed markers or interventions.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.arr.2015.09.005

Cites

461 of 461 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 403 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Age-related and transient declines in cognitive function significantly contribute to functional decline and eventual physical disability.

    “A growing body of evidence suggests that age-related and transient declines in cognitive function significantly contribute to functional decline and eventual development of physical disability.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Atkinson, Cesari, Kritchevsky, Penninx, Fried, Guralnik, and Williamson 2005 source

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    • cites Brummel, Jackson, Pandharipande, Thompson, Shintani, Dittus, Gill, Bernard, Ely, and Girard 2014

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    • cites Deshpande, Metter, Bandinelli, Guralnik, and Ferrucci 2009

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  • Premisecitation

    Specific health conditions including cognitive decline, obesity, sarcopenia, dynapenia, and chronic pain are strongly linked to physical function.

    “Specifically, a growing body of evidence indicates specific conditions including cognitive decline, obesity, sarcopenia, dynapenia, chronic pain, are strongly linked to physical function.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Anton, Karabetian, Naugle, and Buford 2013

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    • cites Buford, Anton, Judge, Marzetti, Wohlgemuth, Carter, Leeuwenburgh, Pahor, and Manini 2010a

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  • Premisecitation

    Cognitive decline is associated with increased rates of injury, hospitalization, dependence on assisted living, and mortality.

    “Given the association between cognitive decline and increased rates of injury, hospitalization, dependence on assisted living, and mortality,”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Boockvar, Signor, Ramaswamy, and Hung 2013

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    • cites Brummel, Jackson, Pandharipande, Thompson, Shintani, Dittus, Gill, Bernard, Ely, and Girard 2014

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    • cites Woods, Mark, Pitts, and Mennemeier 2011

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  • Premisecitation

    Grip strength below 26 kg for men or 16 kg for women is highly predictive of mobility disability.

    “For example, grip strength less than 26kg or 16kg for men and women respectively is highly predictive of mobility disability.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Alley, Shardell, Peters, McLean, Dam, Kenny, Fragala, Harris, Kiel, Guralnik, Ferrucci, Kritchevsky, Studenski, Vassileva, and Cawthon 2014 source

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  • Premisecitation

    Muscle atrophy may impair physiological functions including glucose regulation, hormone production, and cellular communication.

    “While impaired locomotion is certainly the hallmark concern of sarcopenia, muscle atrophy may impair other physiological functions including glucose regulation, hormone production, and cellular communication.”
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    • cites Moon 2014 source

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  • Classified as probably not a substantial claim. 42

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    Premisecitation

    Scores on the Short Physical Performance Battery and walking speed predict onset of difficulty in activities of daily living and disability in community-dwelling older adults.

    “Scores on the SPPB and walking speed have been found to predict onset of difficulty in activities of daily living (Wennie Huang, Perera, VanSwearingen, and Studenski 2010) and disability in community-dwelling older adults.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Wennie Huang, Perera, VanSwearingen, and Studenski 2010

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    • cites Albert, Bear-Lehman, and Anderson 2014

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    • cites Guralnik, Ferrucci, Pieper, Leveille, Markides, Ostir, Studenski, Berkman, and Wallace 2000 source

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    Premisecitation

    Obesity contributes to the progression of sarcopenia and is directly linked to increased risk of physical disability.

    “Moreover, obesity has been identified as a contributor to the progression of sarcopenia (Buford, Anton, Judge, Marzetti, Wohlgemuth, Carter, Leeuwenburgh, Pahor, and Manini 2010a) and directly linked to an increased risk of physical disability.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Buford, Anton, Judge, Marzetti, Wohlgemuth, Carter, Leeuwenburgh, Pahor, and Manini 2010a

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    • cites Figaro, Kritchevsky, Resnick, Shorr, Butler, Shintani, Penninx, Simonsick, Goodpaster, Newman, Schwartz, and Harris 2006

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  • May combine two claims.

    Premisecitation

    Walking speed is a strong surrogate marker of overall health and predicts maintenance of physical independence in older adults.

    “For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging.”
    • Also stated in: § 1. Introduction · plain
      “For example, mobility performance (i.e., walking speed) has emerged as a surrogate marker of overall health and functional ability among older adults.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cesari 2011

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    Premisecitation

    No agreed definition of successful aging exists, and the absence of clear defining characteristics has hindered cross-study comparison and slowed progress in aging research.

    “The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research.”
    • Also stated in: § 1. Introduction · plain
      “Such a consensus definition does not currently exist, and the construct of successful aging remains an evolving concept without a clear set of metrics to define this phenomenon.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Cosco, Prina, Perales, Stephan, and Brayne 2014

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    • cites Depp and Jeste 2006 source

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    Premisecitation

    Small improvements in walking speed above 0.05 m/sec and in Short Physical Performance Battery score above 0.5 points correspond to meaningful improvements in activities of daily living.

    “Moreover, small improvements in walking speed (Δ > 0.05 m/sec) and performance on the SPPB (Δ > 0.5 points) have been found to translate to meaningful improvements in performance of activities of daily living (e.g., stair climbing, walking a block).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Perera, Mody, Woodman, and Studenski 2006 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The Short Physical Performance Battery assesses balance, strength, and walking speed and combines them into an overall physical function score from 0 to 12.

    “The SPPB assesses multiple aspects of lower extremity function including balance, strength, and walking speed and incorporates performance on these three dimensions into an overall physical function score (range = 0 – 12 points).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Guralnik, Simonsick, Ferrucci, Glynn, Berkman, Blazer, Scherr, and Wallace 1994 source

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    Premisecitation

    The Short Physical Performance Battery is a commonly used and well-validated measure of physical function in older adults.

    “Another commonly used and well validated measure of physical function in older adults is the Short Physical Performance Battery (SPPB).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Guralnik, Simonsick, Ferrucci, Glynn, Berkman, Blazer, Scherr, and Wallace 1994 source

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    Premisecitation

    Slow walking speed, below 1 m/sec or below 0.8 m/sec, and reductions in walking speed strongly predict functional decline, major health outcomes, and mortality in older adults.

    “Accumulating evidence indicates slow walking speed (<1 m/sec indicating a high risk and < 0.8 m/sec indicating a very high risk), as well as reductions in walking speed, strongly predict functional decline, major health outcomes, and mortality in older adults.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Abellan Van, Rolland, Andrieu, Bauer, Beauchet, Bonnefoy, Cesari, Donini, Gillette, Inzitari, Nourhashemi, Onder, Ritz, Salva, Visser, and Vellas 2009 source

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    • cites Cesari, Kritchevsky, Penninx, Nicklas, Simonsick, Newman, Tylavsky, Brach, Satterfield, Bauer, Visser, Rubin, Harris, and Pahor 2005

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    • cites Studenski, Perera, Patel, Rosano, Faulkner, Inzitari, Brach, Chandler, Cawthon, Connor, Nevitt, Visser, Kritchevsky, Badinelli, Harris, Newman, Cauley, Ferrucci, and Guralnik 2011

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    Premisecitation

    Obesity contributes to cognitive decline, which in turn contributes to increased risk of disability.

    “Obesity also contributes to cognitive decline,(Bhargava, Weiner, Hynan, Diaz-Arrastia, and Lipton 2006;Riekse, Leverenz, McCormick, Bowen, Teri, Nochlin, Simpson, Eugenio, Larson, and Tsuang 2004) which in turn contributes to increased risk of disability.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bhargava, Weiner, Hynan, Diaz-Arrastia, and Lipton 2006

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    • cites Riekse, Leverenz, McCormick, Bowen, Teri, Nochlin, Simpson, Eugenio, Larson, and Tsuang 2004

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    • cites Deshpande, Metter, Bandinelli, Guralnik, and Ferrucci 2009

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    Premisecitation

    Excess adiposity increases production of reactive oxygen species and inflammatory cytokines, damages mitochondria, and adversely affects cellular quality control, which can accelerate functional decline in older adults.

    “Excess adiposity leads to an increased production of reactive oxygen species and inflammatory cytokines, damaging mitochondria and adversely affecting cellular quality control processes, (Bayeva, Gheorghiade, and Ardehali 2013;Verdejo, del, Troncoso, Gutierrez, Toro, Quiroga, Pedrozo, Munoz, Garcia, Castro, and Lavandero 2012) which can further accelerate the process of functional decline in older”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bayeva, Gheorghiade, and Ardehali 2013

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    • cites Verdejo, del, Troncoso, Gutierrez, Toro, Quiroga, Pedrozo, Munoz, Garcia, Castro, and Lavandero 2012

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    • cites Naugle, Higgins, and Manini 2012

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    Premisecitation

    Chronic pain is highly prevalent in older adults, with estimates as high as 70% in community settings and up to 80% in nursing homes.

    “Chronic pain is a highly prevalent condition in older adults with estimates as high as 70% in community settings and up to 80% in nursing homes.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Ferrell, Whedon, and Rollins 1995

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    • cites Helme and Gibson 2001

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    • cites Karttunen, Turunen, Ahonen, and Hartikainen 2014

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    Sarcopenia has been linked to elevated healthcare costs.

    “Because of the costs associated with caring for an individual with compromised function, sarcopenia has been linked to elevated healthcare costs.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Janssen, Shepard, Katzmarzyk, and Roubenoff 2004 source

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  • May combine two claims.

    Premisecitation

    Sarcopenia is associated with development of functional disability and may lead to loss of independence.

    “Sarcopenia is a major healthcare concern for older adults, (Buford, Anton, Judge, Marzetti, Wohlgemuth, Carter, Leeuwenburgh, Pahor, and Manini 2010a) as it is associated with the development of functional disability (Janssen, Shepard, Katzmarzyk, and Roubenoff 2004;Visser, Goodpaster, Kritchevsky, Newman, Nevitt, Rubin, Simonsick, and Harris 2005) and may lead to the loss of independence.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Buford, Anton, Judge, Marzetti, Wohlgemuth, Carter, Leeuwenburgh, Pahor, and Manini 2010a

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    • cites Janssen, Shepard, Katzmarzyk, and Roubenoff 2004 source

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    • cites Visser, Goodpaster, Kritchevsky, Newman, Nevitt, Rubin, Simonsick, and Harris 2005 source

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    Premisereasoning

    Patients with sarcopenia before disease diagnosis may have impaired recovery from surgery or increased risk of mortality.

    “As a result, patients with sarcopenia prior to disease diagnosis may face impaired recovery from surgery (Rutan and Herndon 1990) or increased risk of mortality.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Rutan and Herndon 1990

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    • cites Prado, Baracos, McCargar, Reiman, Mourtzakis, Tonkin, Mackey, Koski, Pituskin, and Sawyer 2009

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    • Rests on an assumption: Muscle tissue provides the body's only major reserve of readily available amino acids.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Knee osteoarthritis is the most common chronic pain condition and the leading cause of disability among older adults.

    “Of the types of pain experienced, knee osteoarthritis represents the most common chronic pain condition and the leading cause of disability among older adults.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Neogi and Zhang 2013

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    Premisecitation

    Older adults are at increased risk for under treatment of pain and for adverse effects when pain treatment is provided.

    “Complicating matters, older adults are also at increased risk for under treatment of pain and for adverse effects when pain treatment is provided.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Helme and Gibson 2001

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    • cites Karttunen, Turunen, Ahonen, and Hartikainen 2014

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    Premisecitation

    Chronic pain significantly contributes to functional decline and activity limitation, adversely affects quality of life, and is associated with increased morbidity and mortality.

    “Chronic pain significantly contributes to functional decline and activity limitation, (Fletcher, Guthrie, Berg, and Hirdes 2010;Pisters, Veenhof, van Dijk, Heymans, Twisk, and Dekker 2012;Rossi, Pereira, Driusso, Rebelatto, and Ricci 2013;White, Felson, Niu, Nevitt, Lewis, Torner, and Neogi 2011) adversely affects quality of life, and is associated with increased morbidity and mortality.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Fletcher, Guthrie, Berg, and Hirdes 2010

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    • cites Pisters, Veenhof, van Dijk, Heymans, Twisk, and Dekker 2012

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    • cites Rossi, Pereira, Driusso, Rebelatto, and Ricci 2013

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  • Classified as probably not a substantial claim.

    Interpretationcitation

    The disconnect between muscle mass and weakness may be explained by age-dependent inter- and intramuscular fat infiltration, excitation-contraction coupling, or dysfunctions of the central nervous system or neuromuscular junctions.

    “This suggests that at some level, there is a disconnect between muscle mass and weakness that may theoretically be explained by other factors such as age-dependent inter- and intramuscular fat infiltration (Goodpaster, Carlson, Visser, Kelley, Scherzinger, Harris, Stamm, and Newman 2001;Visser, Kritchevsky, Goodpaster, Newman, Nevitt, Stamm, and Harris 2002), excitation-contraction coupling, (Delb”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Goodpaster, Carlson, Visser, Kelley, Scherzinger, Harris, Stamm, and Newman 2001 source

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    • cites Visser, Kritchevsky, Goodpaster, Newman, Nevitt, Stamm, and Harris 2002 source

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    • cites Delbono 2000

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    • Rests on an assumption: Neither measurement of muscle mass nor muscle index is consistently associated with adverse outcomes.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Physical inactivity is currently the most common behavioral risk factor for obesity in the United States.

    “These trends are concerning as physical inactivity is currently the most common behavioral risk factor for obesity in the United States.”
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    • cites [2008]

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    • cites Physical activity guidelines for Americans 2008

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    Premisecitation

    Leptin resistance predisposes animals to exacerbated diet-induced obesity.

    “Emerging evidence suggests that leptin resistance predisposes animals to exacerbated diet-induced obesity.”
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    • cites Scarpace and Zhang 2009

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    Premisecitation

    A sedentary lifestyle adds to the risk of numerous pathological conditions, many of which appear to accelerate sarcopenia progression.

    “a sedentary lifestyle certainly adds to the risk of numerous pathological conditions, many of which do appear to accelerate sarcopenia progression.(Buford, Anton, Judge, Marzetti,”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Buford et al. 2010a

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    Premisecitation

    Most adults in affluent countries live sedentary lifestyles and spend more than half their waking hours in sedentary pursuits.

    “Most adults in affluent countries live sedentary lifestyles and spend more than half their waking hours in sedentary pursuits.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Cohen, Matthews, Signorello, Schlundt, Blot, and Buchowski 2013

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    • cites Maher, Mire, Harrington, Staiano, and Katzmarzyk 2013

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  • May combine two claims.

    Premisecitation

    Living with chronic pain is stressful, further burdening biological system functioning and ultimately contributing to allostatic overload, accelerated cellular aging, and increased morbidity and mortality.

    “Additionally, living with chronic pain is stressful further burdening biological system functioning, and ultimately contributing to allostatic overload, accelerated cellular aging, and increased morbidity and mortality.”
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    • cites Andersson 2004

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    • cites Sibille, Witek-Janusek, Mathews, and Fillingim 2012

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    • cites Szanton, Allen, Seplaki, Bandeen-Roche, and Fried 2009

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  • May combine two claims.

    Interpretationcitation

    Obese older adults are at greater risk of functional decline than peers with a BMI in the healthy range and represent a high-risk group.

    “Such findings suggest that obese, older adults appear are at greater risk of functional decline compared to peers with a BMI in the healthy range, and therefore represent a high-risk group.”
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    • cites Vincent, Horodyski, Gearen, Vlasak, Seay, Conrad, and Vincent 2012

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    Premisecitation

    Aged rats consume more highly palatable high-fat diet than young rats, leading to exacerbated weight gain mostly as fat.

    “Recent studies have found that aged rats consume a greater amount of highly palatable high-fat (HF) diet than young rats, leading to exacerbated weight gain mostly in the form of fat.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Petervari, Rostas, Soos, Tenk, Miko, Furedi, Szekely, and Balasko 2014

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sleep problems are commonly underdiagnosed.

    “Sleep problems are commonly underdiagnosed (Roth, Coulouvrat, Hajak, Lakoma, Sampson, Shahly, Shillington, Stephenson, Walsh, and Kessler 2011)”
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    • cites Roth et al. 2011

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sleep problems are a significant source of concern in older adults.

    “are a significant source of concern in older adults.(Ory, Smith, Ahn, Jiang, Lorig, and Whitelaw 2014)”
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    • cites Ory et al. 2014

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  • Classified as probably not a substantial claim.

    Premisecitation

    Current definitions mix the health consequences of insufficient moderate-to-vigorous activity with possible adverse effects of prolonged sedentary behavior.

    “current definitions comingle the health consequences associated with lack of moderate-to-vigorous intensity activity with potential adverse health effects of extended periods of physical inactivity (sitting, reclining).(Sedentary Behaviour 2012)”
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    • cites Sedentary Behaviour 2012 source

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    Premisecitation

    A constant oversupply of energy and nutrients can contribute to increased adiposity during aging, which can accelerate functional decline and significantly increase risk for disability.

    “If left unchecked, a constant oversupply of energy and nutrients can contribute to increased adiposity during aging, which can accelerate functional decline and significantly increases risk for disability.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Baumgartner 2000a

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    • cites Blaum, Xue, Michelon, Semba, and Fried 2005b

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  • May combine two claims.

    Premisecitation

    Outdoor air pollution in major population centers is directly responsible for increased mortality and declining health, especially respiratory illness.

    “Outdoor air pollution (i.e., particulate and chemical), in major population centers around the world, is directly responsible for increased mortality and declining health, especially with regards to respiratory illness.(Bentayeb, Simoni, Baiz, Norback, Baldacci, Maio, Viegi, and Annesi-Maesano 2012;Kunzli, Kaiser, Medina, Studnicka, Chanel, Filliger, Herry, Horak, Jr., Puybonnieux-Texier, Quenel,”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bentayeb et al. 2012

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    • cites Kunzli et al. 2000

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    • cites Pope et al. 2009

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    Premisecitation

    Older individuals are particularly susceptible to air pollution because of compromised immune systems and predisposition to respiratory infections, and are vulnerable to increased risk for COPD.

    “Older individuals are particularly susceptible given their compromised immune systems (Bentayeb, Simoni, Baiz, Norback, Baldacci, Maio, Viegi, and Annesi-Maesano 2012) and predisposition to respiratory infections, and as such are vulnerable to increased risk for chronic obstructive pulmonary disease (COPD).(Bentayeb, Simoni, Baiz, Norback, Baldacci, Maio, Viegi, and Annesi-Maesano 2012)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bentayeb et al. 2012

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    Premisecitation

    The Chinese Longitudinal Health Longevity Survey demonstrated that very low seasonal temperature increased the odds of ADL disability by 44% and increased mortality by 32%.

    “The Chinese Longitudinal Health Longevity Survey demonstrated that very low seasonal temperature increased the odds of ADL disability by 44% and increased mortality by 32%.(The CLHLS Research Team 2008)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites The CLHLS Research Team 2008

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    Premisecitation

    The number of medications used tends to increase with age, which can lead to increased morbidity, mortality, and side effects such as falls, cognitive impairment, and sleep disturbances.

    “the number of medications used tends to increase with age, which can lead to increased morbidity, mortality, and side effects such as falls, cognitive impairment, and even sleep disturbances.(Huang, Mallet, Rochefort, Eguale, Buckeridge, and Tamblyn 2012)”
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    • cites Huang et al. 2012

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    Premisecitation

    Epidemiologic studies in older adults show an association between sleep complaints and risk factors for sleep disturbance but little association with older age, suggesting these risk factors rather than aging itself account for much of the increase in insomnia with age.

    “Epidemiologic studies in older adults have demonstrated an association between sleep complaints and risk factors for sleep disturbance (e.g., chronic illness, multiple medical problems, mood disturbance, less physical activity, physical disability) but little association with older age, suggesting that these risk factors, rather than aging per se, account for much of the increase in insomnia with”
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    • cites Luo et al. 2013

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    Premisecitation

    Older adults report earlier bedtime and morning awakening, more night awakenings, more night wakefulness, and more daytime napping.

    “Older adults also report an earlier bedtime and earlier morning awakening, more awakenings during the night, more wakefulness during the night, and more daytime napping.(Grandner, Martin, Patel, Jackson, Gehrman, Pien, Perlis, Xie, Sha, Weaver, and Gooneratne 2012;Pace-Schott EF and Spencer RMC 2013)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Grandner et al. 2012

      Not checked in the free run.

    • cites Pace-Schott EF and Spencer RMC 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Older adults generally have decreased sleep efficiency, stable or decreased total sleep time, and increased sleep latency.

    “older adults generally have decreased sleep efficiency (time asleep divided by time in bed), stable or decreased total sleep time, and increased sleep latency (time to fall asleep).(Grandner, Martin, Patel, Jackson, Gehrman, Pien, Perlis, Xie, Sha, Weaver, and Gooneratne 2012)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Grandner et al. 2012

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Aging is associated with an increased risk for depressive symptoms.

    “Aging is associated with an increased risk for depressive symptoms (Alexopoulos 2005)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Alexopoulos 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Individuals living in neighborhoods with no parks or walking areas engaged less frequently in regular fitness, whereas those with adequate handicap parking were more likely to engage in social and work activities.

    “those individuals living in neighborhoods with no parks or walking areas engaged less frequently in regular fitness whereas those with neighborhoods with adequate handicap parking were more likely to engage in social and work activities.(Gray, Hollingsworth, Stark, and Morgan 2008;White, Jette, Felson, LaValley, Lewis, Torner, Nevitt, and Keysor 2010)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Gray et al. 2008

      Not checked in the free run.

    • cites White et al. 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The World Health Organization estimates that depression is the leading cause of functional disability worldwide.

    “the World Health Organization estimates that depression is the leading cause of functional disability worldwide.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites World Health Organization

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Individuals with functional limitations living in restrictive communities felt limited in their daily activities but did not perform tasks less frequently.

    “individuals with functional limitations living in restrictive communities felt limited in their daily activities but did not perform tasks less frequently.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Keysor et al. 2010

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The mechanisms underlying the relationship between depressive symptoms and functional decline have not been fully elucidated, but likely involve a complex interrelationship of psychosocial, cognitive, and brain changes.

    “The mechanisms underlying the relationship between depressive symptoms and functional decline have not been fully elucidated, but likely involve a complex interrelationship of psychosocial, cognitive, and brain changes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Declines in PGC-1α are associated with reductions in mitochondrial oxidative metabolism, which is associated with poor muscle quality and function.

    “declines in PGC-1α have been associated with reductions in mitochondrial oxidative metabolism which is associated with poor muscle quality and function.(Garnier, Fortin, Zoll, N'Guessan, Mettauer, Lampert, Veksler, and Ventura-Clapier 2005b;Little, Safdar, Bishop, Tarnopolsky, and Gibala 2011;Safdar, Hamadeh, Kaczor, Raha, Debeer, and Tarnopolsky 2010)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Garnier et al. 2005b

      Not checked in the free run.

    • cites Little et al. 2011 source

      Not checked in the free run.

    • cites Safdar et al. 2010 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Depression is associated with cognitive and brain changes, which are known to impact functional abilities.

    “depression is also associated with cognitive and brain changes, (Dotson, Resnick, and Zonderman 2008;Dotson, Szymkowics, Kirton, McLaren, Green, and Rohani 2014;Dotson, Zonderman, Davatzikos, Kraut, and Resnick 2009;Dotson, Zonderman, Kraut, and Resnick 2013) which are also known to impact functional abilities.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Dotson et al. 2008

      Not checked in the free run.

    • cites Dotson et al. 2014

      Not checked in the free run.

    • cites Dotson et al. 2009

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Several biological factors have been associated with the pathogenesis of functional decline during aging and physical disability in non-acute disease conditions, but the exact mechanisms remain largely undefined.

    “Several biological factors have been associated with the pathogenesis of functional decline during aging and physical disability (in non-acute disease conditions), but the exact mechanisms contributing to age-related functional decline remain largely undefined.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    According to the mitochondrial theory of aging, overproduction of ROS from the electron transport chain within the inner mitochondrial membrane drives the mitochondrial dysfunction associated with age-related muscle atrophy.

    “According to this theory, an overproduction of ROS from the electron transport chain (ETC) within the inner mitochondrial membrane are the driving force for the mitochondrial dysfunction associated with age-related muscle atrophy.(Harman 1972;Miquel, Economos, Fleming, and Johnson Jr 1980)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Harman 1972

      Not checked in the free run.

    • cites Miquel et al. 1980

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Self-efficacy and control beliefs are associated with fear of falling, gait speed, balance, worse pain management, and limitations in ADLs.

    “self-efficacy and control beliefs are associated with fear of falling, gait speed, balance, worse pain management, and limitations in ADLs.(Dark-Freudeman, Ebner, and West 2014)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Dark-Freudeman et al. 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The mitochondrial theory of aging proposes that cumulative damage caused by oxidants can alter mtDNA.

    “the mitochondrial theory of aging proposes that cumulative damage caused by the production of oxidants can alter MtDNA (e.g., point mutations and increase deletions).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Harman 1972

      Not checked in the free run.

    • cites Miquel et al. 1980

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Abnormalities in mitochondrial enzyme activity, lower mitochondrial protein synthesis rates, oxidative capacity, and ATP synthesis have been observed in the skeletal muscle of older persons.

    “Abnormalities in mitochondrial enzyme activity, (Rooyackers, Adey, Ades, and Nair 1996;Short, Bigelow, Kahl, Singh, Coenen-Schimke, Raghavakaimal, and Nair 2005a) lower mitochondrial protein synthesis rates,(Rooyackers, Adey, Ades, and Nair 1996) oxidative capacity, and adenosine triphosphate (ATP) synthesis(Short, Bigelow, Kahl, Singh, Coenen-Schimke, Raghavakaimal, and Nair 2005a) have been”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Rooyackers et al. 1996 source

      Not checked in the free run.

    • cites Short et al. 2005a

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mitochondrial dysregulation occurs in aging tissues, including altered gene expression pathways, aberrant quality control processes, and activation of myonuclear cell death.

    “Abundant evidence points to mitochondrial dysregulation in aging tissues including altered gene expression pathways, aberrant quality control processes, and activation of myonuclear cell death.(Calvani, Joseph, Adhihetty, Miccheli, Bossola, Leeuwenburgh, Bernabei, and Marzetti 2013)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Calvani et al. 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Autophagy is an important but underexplored biological process affecting age-related changes in muscle composition and functional decline.

    “The cellular quality control (QC) process of autophagy represents an important but underexplored biological process affecting age-related changes in muscle composition and functional decline.(Baumgartner 2000b;Blaum, Xue, Michelon, Semba, and Fried 2005a;Cesari, Kritchevsky, Baumgartner, Atkinson, Penninx, Lenchik, Palla, Ambrosius, Tracy, and Pahor 2005)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Baumgartner 2000b

      Not checked in the free run.

    • cites Blaum et al. 2005a

      Not checked in the free run.

    • cites Cesari et al. 2005

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Muscle-specific deletion of Mfn1 and Mfn2 results in accumulation of mtDNA mutations and deletions, reduced mtDNA content, and muscle atrophy.

    “Muscle-specific deletion of Mfn1 and Mfn2 results in the accumulation of mtDNA mutations and deletions, reduced mtDNA content, as well as muscle atrophy.(Chen, Vermulst, Wang, Chomyn, Prolla, McCaffery, and Chan 2010)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chen et al. 2010 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Evidence to date strongly implicates mitochondria as having a pivotal role in the pathogenesis of age-related functional decline, and reductions in autophagy appear to be a critical biological mechanism affecting the collective function of the mitochondrial pool.

    “Thus, evidence to date strongly implicates the mitochondria as having a pivotal role in the pathogenesis of age-related functional decline,(Coen, Jubrias, Distefano, Amati, Mackey, Glynn, Manini, Wohlgemuth, Leeuwenburgh, Cummings, Newman, Ferrucci, Toledo, Shankland, Conley, and Goodpaster 2013) and reductions in autophagy appear to be a critical biological mechanism affecting the collective”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Coen et al. 2013 source

      Not checked in the free run.

    • cites Weber and Reichert 2010

      Not checked in the free run.

    • cites Zhu et al. 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Damage to mitochondrial proteins and lipids may contribute to mitochondrial dysfunction by affecting oxidative phosphorylation and ETC activity and by altering susceptibility to apoptosis.

    “damage to mitochondrial proteins and lipids may also contribute to mitochondrial dysfunction by not only affecting oxidative phosphorylation and ETC activity but also by altering the susceptibility of Mt to apoptosis.(Conley, Marcinek, and Villarin 2007;Dirks and Leeuwenburgh 2002;Gonzalvez and Gottlieb 2007;Paradies, Petrosillo, Pistolese, and Ruggiero 2002;Shidoji, Hayashi, Komura, Ohishi, and Y”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Conley et al. 2007

      Not checked in the free run.

    • cites Dirks and Leeuwenburgh 2002

      Not checked in the free run.

    • cites Gonzalvez and Gottlieb 2007

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Impairments in autophagy can result in accumulation of damaged mitochondria, reductions in bioenergetic status, and myocyte apoptosis, which may be reflected in decreased muscle strength and slower walking speed observed with aging.

    “Impairments in autophagy can result in the accumulation of damaged mitochondria,(Brunk and Terman 2002;Terman and Brunk 2005) reductions in the bioenergetic status of the cell,(Marzetti, Lees, Wohlgemuth, and Leeuwenburgh 2009;Pyo, Yoo, and Jung 2013) and in myocyte apoptosis,(Wohlgemuth, Calvani, and Marzetti 2014) which may be reflected in decreased muscle strength(Buford, Anton, Judge, Marzetti”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Brunk and Terman 2002

      Not checked in the free run.

    • cites Terman and Brunk 2005 source

      Not checked in the free run.

    • cites Marzetti et al. 2009

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There are over 80 pathogenic mutations in POLG in humans, including PEO, Alpers syndrome, and ataxia.

    “There are over 80 pathogenic mutations in POLG in humans, including progressive external ophthalmoplegia (PEO), Alpers syndrome, and ataxia.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Kujoth et al. 2007

      Not checked in the free run.

    • cites Mancuso et al. 2004

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Markers of inflammation in blood and specific tissues are associated with impaired motor and cognitive function, suggesting that the pro-inflammatory phenotype impairs older individuals' ability to cope with age-related stressors and thus contributes to functional decline.

    “Markers of inflammation in the blood and in specific tissues are associated with impaired motor and cognitive function (Blalock, Chen, Sharrow, Herman, Porter, Foster, and Landfield 2003;Speisman, Kumar, Rani, Foster, and Ormerod 2013;Zeier, Madorsky, Xu, Ogle, Notterpek, and Foster 2011) suggesting that the pro-inflammatory phenotype impairs the ability of older individuals to cope with age”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Blalock et al. 2003 source

      Not checked in the free run.

    • cites Speisman et al. 2013

      Not checked in the free run.

    • cites Zeier et al. 2011

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    More than 100 different deletions of mtDNA have been associated with mitochondrial disorders.

    “more than 100 different deletions of mtDNA have been associated with mitochondrial disorders.(Chinnery, Elliott, Green, Rees, Coulthard, Turnbull, and Griffiths 2000;Kujoth, Bradshaw, Haroon, and Prolla 2007;Someya and Prolla 2010)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Chinnery et al. 2000

      Not checked in the free run.

    • cites Kujoth et al. 2007

      Not checked in the free run.

    • cites Someya and Prolla 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PGC-1α is known as the master regulator of mitochondrial biogenesis because it can coactivate and upregulate coordinated expression of genes required for substrate metabolism and biogenesis.

    “PGC-1α, known as the master regulator of mitochondrial biogenesis because of its ability to coactivate and upregulate the coordinated expression of a number of genes required for substrate metabolism and biogenesis.(Handschin and Spiegelman 2006)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Handschin and Spiegelman 2006

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Nuclear-encoded POLG is the only known DNA polymerase in mitochondria and has conserved polymerase and exonuclease domains that repair mtDNA mutations.

    “Nuclear-encoded POLG is the only known DNA polymerase in mitochondria and has conserved polymerase and exonuclease domains, which repair mtDNA mutations.(Kujoth, Bradshaw, Haroon, and Prolla 2007)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kujoth et al. 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Specific mutations in mtDNA cause mitochondrial disorders in humans including MELAS and MERRF.

    “specific mutations in mtDNA cause a number of mitochondrial disorders in humans including mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS), and myoclonic epilepsy and ragged red fibers (MERRF).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The mammalian mitochondrial genome consists of 37 genes, encoding 13 proteins of the electron transport oxidative phosphorylation system.

    “The mammalian mitochondrial genome consists of 37 genes, encoding 13 proteins of the electron transport oxidative phosphorylation system.(Anderson, Bankier, Barrell, de Bruijn, Coulson, Drouin, Eperon, Nierlich, Roe, Sanger, Schreier, Smith, Staden, and Young 1981)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Anderson et al. 1981

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Most reported POLG mutations are recessive, commonly found with other POLG mutations, and associated with symptoms including ophthalmoplegia, cataracts, progressive muscle weakness, parkinsonism, premature ovarian failure, male infertility, hearing loss, and cardiac dysfunction.

    “Most reported mutations are recessive, commonly found in combination with other mutations in POLG, and associated with a variety of symptoms including ophthalmoplegia, cataracts, progressive muscle weakness, parkinsonism, premature”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Kujoth et al. 2007

      Not checked in the free run.

    • cites Mancuso et al. 2004

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NF-κB signaling activation increases muscle protein degradation and inhibits myogenesis, except in very late differentiation where it promotes homeostasis.

    “activation of NF-κB signaling increases muscle protein degradation and inhibits myogenesis,(Li, Malhotra, and Kumar 2008;Merritt, Stec, Thalacker-Mercer, Windham, Cross, Shelley, Craig, Kosek, Kim, and Bamman 2013) except in very late differentiation where it promotes homeostasis.(Li, Malhotra, and Kumar 2008)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Li, Malhotra, and Kumar 2008

      Not checked in the free run.

    • cites Merritt, Stec, Thalacker-Mercer, Windham, Cross, Shelley, Craig, Kosek, Kim, and Bamman 2013 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Estrogen and testosterone replacement may reduce risk for osteoporosis, cardiovascular disease, and Alzheimer's disease.

    “estrogen and testosterone replacement may reduce risk for osteoporosis, cardiovascular disease, and Alzheimer’s disease.(Nguyen, Dolomie-Fagour, Georges, and Corcuff 2008)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nguyen, Dolomie-Fagour, Georges, and Corcuff 2008

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This apoptotic process begins in middle adulthood and accelerates with increasing age.

    “This process begins in middle-adulthood and accelerates with increasing age.(Larsson, Grimby, and Karlsson 1979;Mittal and Logmani 1987)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Larsson, Grimby, and Karlsson 1979

      Not checked in the free run.

    • cites Mittal and Logmani 1987

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Smart homes have been used for monitoring falls in older adults using ambient motion sensors, pressure sensors in floor tiles, and floor vibration detection through audio analysis.

    “smart homes have been used for monitoring falls in older adults using ambient motion sensors, pressure sensors placed in floor tiles, as well as floor vibration detection through audio analysis (Alwan, Rajendran, Kell, Mack, Dalal S, Wolfe, and Felder 2006)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Alwan, Rajendran, Kell, Mack, Dalal S, Wolfe, and Felder 2006

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although the weight loss plus exercise group showed the greatest improvements, the DR weight loss only group performed significantly better than the control group on measures of physical function.

    “Although the weight loss plus exercise group showed the greatest improvements, the DR weight loss only group performed significantly better than the control group on measures of physical function.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Villareal, Chode, Parimi, Sinacore, Hilton, Armamento-Villareal, Napoli, Qualls, and Shah 2011 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Phenotype (obesity) and medication use each had significant yet independent influences on participants' responsiveness to training.

    “Accordingly, phenotype (i.e. obesity) and medication use each had significant yet independent influences on the responsiveness of the participants to training.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Diet-induced weight loss may exacerbate sarcopenia progression and further impair physical function.

    “and thus may exacerbate the progression of sarcopenia and further impair physical function.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Benefits of exercise are not observed in all individuals and change in performance is quite variable.

    “However, these benefits are not observed in all individuals and the change in performance is quite variable.(Kohrt, Malley, Coggan, Spina, Ogawa, Ehsani, Bourey, Martin, III, and Holloszy 1991)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kohrt, Malley, Coggan, Spina, Ogawa, Ehsani, Bourey, Martin, III, and Holloszy 1991

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    Each of these findings was independent of differences in confounding characteristics as well as the volume of exercise performed.

    “Importantly, each of these findings was independent of differences in confounding characteristics as well as the volume of exercise performed.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Buford, Manini, Hsu, Cesari, Anton, Nayfield, Stafford, Church, Pahor, and Carter 2012

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a three-month dietary weight loss program for obese older women, participants achieved significant reductions in body weight and body composition parameters, in both fat and fat-free mass, and overall physical performance improved significantly.

    “At follow up, participants achieved a significant reduction in body weight and body composition parameters, in both fat and fat-free mass, and overall physical performance, as measured by a battery of physical tasks including 400-meter walk and stair climb, improved significantly.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jensen, Roy, Buchanan, and Berg 2004

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Exercise may be necessary but insufficient for preserving physical function and preventing disability among many older adults.

    “These findings suggest that exercise may be necessary, but insufficient, for preserving physical function and preventing disability among many older adults.(Keysor and Brembs 2011)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Keysor and Brembs 2011

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is clear evidence that older adults can adhere to long-term home-based interventions while maintaining and improving high levels of engagement.

    “there is clear evidence that older adults can adhere to long-term (e.g., 3 month) home-based interventions while maintaining and improving high levels of engagement. (Belchior, Marsiske, Sisco, Yam, and Mann 2012)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Belchior, Marsiske, Sisco, Yam, and Mann 2012

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A secondary benefit of video games seems to be mood improvement, with reduced subsyndromal depression likely to further promote engagement in subsequent health behaviors.

    “A secondary benefit of video games seems to be mood improvement (Rosenberg, Depp, Vahia, Reichstadt, Palmer, Kerr, Norman, and Jeste 2010;Studenski, Perera, Hile, Keller, Spadola-Bogard, and Garcia 2010), with reduced levels of subsyndromal depression likely to further promote engagement in subsequent health behaviors.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Rosenberg, Depp, Vahia, Reichstadt, Palmer, Kerr, Norman, and Jeste 2010

      Not checked in the free run.

    • cites Studenski, Perera, Hile, Keller, Spadola-Bogard, and Garcia 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    It has been suggested that metformin recapitulates the effects of dietary restriction.

    “It has also been suggested that metformin recapitulates the effects of dietary restriction.(Onken and Driscoll 2010)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Onken and Driscoll 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationcitation

    These findings support deploying home-based interventions, especially in computer-assisted and gamified forms.

    “Such findings more broadly support the concept of deploying home based interventions, especially in computer-assisted and gamified forms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Epidemiologic evidence from the Women's Health and Aging Study and the Systematic Assessment of Geriatric drug use via Epidemiology Study indicated that older adults using ACE inhibitors had attenuated declines in walking speed and fewer ADL limitations compared to non-users.

    “Epidemiologic evidence from the Women’s Health and Aging Study and the Systematic Assessment of Geriatric drug use via Epidemiology Study indicated that, compared to non-users, older adults using ACE inhibitors displayed attenuated declines in walking speed and fewer limitations in ADLs.(Gambassi, Lapane, Sgadari, Carbonin, Gatsonis, Lipsitz, Mor, and Bernabei 2000;Onder, Penninx, Balkrishnan, F”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Gambassi, Lapane, Sgadari, Carbonin, Gatsonis, Lipsitz, Mor, and Bernabei 2000

      Not checked in the free run.

    • cites Onder, Penninx, Balkrishnan, Fried, Chaves, Williamson, Carter, Di, Guralnik, and Pahor 2002 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Engaging in exergames can improve cardiovascular risk indices, energy expenditure, walk time, and balance in middle-aged and older adults.

    “There is evidence that, via engaging in exergames, middle aged and older adults can improve cardiovascular risk indices, energy expenditure, walk time, and balance. (Agmon, Perry, Phelan, Demiris, and Nguyen 2011;Guderian, Borreson, Sletten, Cable, Stecker, Probst, and Dalleck 2010;Studenski, Perera, Hile, Keller, Spadola-Bogard, and Garcia 2010)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Agmon, Perry, Phelan, Demiris, and Nguyen 2011

      Not checked in the free run.

    • cites Guderian, Borreson, Sletten, Cable, Stecker, Probst, and Dalleck 2010

      Not checked in the free run.

    • cites Studenski, Perera, Hile, Keller, Spadola-Bogard, and Garcia 2010

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    tDCS may serve as an independent and/or adjunctive therapy that can alleviate factors limiting mobility and improve interventions aimed at enhancing physical and cognitive function in older adults.

    “Thus, tDCS may serve as either an independent and/or adjunctive therapy that has the potential to alleviate factors limiting mobility and improve interventions aimed at enhancing physical and cognitive function in older adults.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Lifestyle interventions using physical exercise and diet attenuate declines in physical function and health, and interventions aimed at slowing or preventing age-related decline in thinking and memory skills also hold promise for improving physical function.

    “While lifestyle interventions using physical exercise and diet have been found to attenuate declines in physical function and health, interventions aimed at slowing or preventing age-related decline in thinking and memory skills also hold promise for improving physical function.(Ball, Berch, Helmers, Jobe, Leveck, Marsiske, Morris, Rebok, Smith, Tennstedt, Unverzagt, and Willis 2002;Ball and Ows”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Ball, Berch, Helmers, Jobe, Leveck, Marsiske, Morris, Rebok, Smith, Tennstedt, Unverzagt, and Willis 2002 source

      Not checked in the free run.

    • cites Ball and Owsley 1993

      Not checked in the free run.

    • cites Marsiske, Dzierzewski, Thomas, Kasten, Jones, Johnson, Willis, Whitfield, Ball, and Rebok 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This approach has the benefit of requiring minimal effort on the part of patients, an important point given that the initial effort required to begin an intervention program is a primary barrier to lifestyle-based treatments.

    “This approach has the benefit of requiring minimal effort on the part of patients, an important point given that the initial effort required to begin an intervention program is a primary barrier to lifestyle-based treatments.(Lees, Clarkr, Nigg, and Newman 2005)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lees, Clarkr, Nigg, and Newman 2005

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The popular drug metformin could potentially improve function and reduce frailty risk in older adults with type 2 diabetes.

    “the popular drug metformin could potentially improve function and reduce frailty risk in older adults with type 2 diabetes.(Wang, Lorenzo, and Espinoza 2014)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wang, Lorenzo, and Espinoza 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some researchers have investigated providing interventions and means for overcoming physical limitations by integrating assistive robots within environments.

    “Some researchers also have investigated providing interventions and means for overcoming physical limitations, e.g. by integrating assistive robots within the environments. (Graf, Heyer, Klein, and Wallhoff 2013)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Graf, Heyer, Klein, and Wallhoff 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Initial evidence suggests both fitness and broad cognitive improvements with custom exergames.

    “initial evidence suggests both fitness and broad cognitive improvements with custom games. (Bamidis, Vivas, Styliadis, Frantzidis, Klados, Schlee, Siountas, and Papageorgiou 2014;Maillot, Perrot, and Hartley 2012)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Bamidis, Vivas, Styliadis, Frantzidis, Klados, Schlee, Siountas, and Papageorgiou 2014

      Not checked in the free run.

    • cites Maillot, Perrot, and Hartley 2012

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted).

    Premisecitation

    Exercise may stimulate adaptations to pharmaceuticals that are not observed in response to the drug alone.

    “Others have proposed that exercise may stimulate adaptations to pharmaceuticals that are not observed in response to the drug alone.(Booth and Laye 2010)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Booth and Laye 2010

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice, an oral PPARδ agonist had no effect when given in isolation but increased exercise tolerance when given with an exercise-training regimen.

    “despite showing no effect when given to mice in isolation, an oral PPARδ agonist increased exercise tolerance when given in conjunction with an exercise-training regimen.(Narkar, Downes, Yu, Embler, Wang, Banayo, Mihaylova, Nelson, Zou, Juguilon, Kang, Shaw, and Evans 2008)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Narkar, Downes, Yu, Embler, Wang, Banayo, Mihaylova, Nelson, Zou, Juguilon, Kang, Shaw, and Evans 2008

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Use of dietary supplements is rising among middle-aged and older people.

    “Given the increasing popularity of these products among middle-age and older adults,(Mehlman, Binstock, Juengst, Ponsaran, and Whitehouse 2004)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mehlman, Binstock, Juengst, Ponsaran, and Whitehouse 2004

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Group sequential designs became feasible in the last quarter of the twentieth century.

    “Group sequential designs became practical in the final quarter of the 20th century.(Jennison and Turnbull B.W. 2000)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jennison and Turnbull B.W. 2000

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Resveratrol acts on many targets and has broad systemic effects resembling those of caloric restriction.

    “resveratrol has been found to activate a wide variety of targets, and produces broad, systemic effects that are very similar to caloric restriction,(Marzetti, Wohlgemuth, Anton, Bernabei, Carter, and Leeuwenburgh 2009;Testa, Biasi, Poli, and Chiarpotto 2014)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Marzetti, Wohlgemuth, Anton, Bernabei, Carter, and Leeuwenburgh 2009

      Not checked in the free run.

    • cites Testa, Biasi, Poli, and Chiarpotto 2014

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Resveratrol seems to engage pathways similar to dietary restriction while avoiding muscle loss.

    “because it appears to activate similar pathways as DR without leading to muscle loss.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Marzetti, Wohlgemuth, Anton, Bernabei, Carter, and Leeuwenburgh 2009

      Not checked in the free run.

    • cites Testa, Biasi, Poli, and Chiarpotto 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oxytocin modulates higher-order cognitive processing.

    “the hormone oxytocin has modulatory effects on higher-order cognitive processing (Meyer-Lindenberg, Domes, Kirsch, and Heinrichs 2011)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Meyer-Lindenberg, Domes, Kirsch, and Heinrichs 2011 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Resveratrol's favorable biological effects have been shown in several species and linked to better performance on functional and health-span measures.

    “These beneficial biological effects have been demonstrated across multiple species, and have been associated with improvements on a variety of functional tasks and health-span measures.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Baur, Pearson, Price, Jamieson, Lerin, Kalra, Prabhu, Allard, Lopez-Lluch, Lewis, Pistell, Poosala, Becker, Boss, Gwinn, Wang, Ramaswamy, Fishbein, Spencer, Lakatta, Le, Shaw, Navas, Puigserver, Ingram, de, and Sinclair 2006 source

      Not checked in the free run.

    • cites Greer and Brunet 2009

      Not checked in the free run.

    • cites Long, Gao, Sun, Liu, and Zhao-Wilson 2009

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxytocin affects the cardiovascular system, including improving vasculature, possibly through interaction with sex hormones.

    “and effects on the cardiovascular system in that it has been found to improve the vasculature, possibly in interaction with sex hormones (Gimpl and Fahrenholz 2001)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gimpl and Fahrenholz 2001 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    These data demonstrate the potential impact of adjunctive ACE inhibitor strategy in preserving function and mobility in older adults, and highlight the value of adjunctive intervention strategies.

    “These data demonstrate the potential impact of this adjunctive strategy in preserving function and mobility in older adults, and helps to highlight the value of adjunctive intervention strategies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Annual US expenditure on dietary supplements exceeds 12 billion dollars.

    “Estimates indicate that Americans spend over 12 billion dollars per year on nutritional supplements (Blanck, Khan, and Serdula 2001)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Blanck, Khan, and Serdula 2001

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    This pattern also applies to trials of interventions for physical function in older adults.

    “This is also true for evaluating interventions to enhance function in older adults.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    More efficient trial designs could raise the success rate.

    “The success rate could be improved with more efficient clinical trial designs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Clinical trials are growing more costly and have low success rates.

    “Clinical trials are becoming increasingly expensive while the success rate remains low. (DiMasi, Hansen, and Grabowski 2003;Walker and Newell 2009)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites DiMasi, Hansen, and Grabowski 2003

      Not checked in the free run.

    • cites Walker and Newell 2009

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Projected annual growth in supplement sales is about 10%.

    “sales of these products are projected to continue to increase by approximately 10% per year. (Goldman 2001)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Goldman 2001

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxytocin improves weight control and insulin sensitivity.

    “and benefits weight control and insulin sensitivity.(Zhang, Wu, Chen, Chen, Xu, Wu, and Cai 2013)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zhang, Wu, Chen, Chen, Xu, Wu, and Cai 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxytocin can reach the human brain via nasal spray and affect central functions.

    “which can be delivered to the human brain by the use of nasal spray, tapping into central functions.(Born, Lange, Kern, McGregor, Bickel, and Fehm 2002)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Born, Lange, Kern, McGregor, Bickel, and Fehm 2002

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Group sequential designs with unblinded sample-size re-estimation appeared in the new millennium.

    “Group sequential designs with unblinded sample size re-estimation were introduced in the new millennium. (Cui, Hung, and Wang 1999;Lehmacher and Wassmer 1999;Proschan and Hunsberger 1995)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Cui, Hung, and Wang 1999

      Not checked in the free run.

    • cites Lehmacher and Wassmer 1999

      Not checked in the free run.

    • cites Proschan and Hunsberger 1995

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Group sequential designs allow early stopping for efficacy or futility and flexible timing and number of interim analyses.

    “Such designs permit early termination of the study for efficacy or futility with flexibility to alter number and spacing of interim analyses.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jennison and Turnbull B.W. 2000

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Various health conditions, behavioral factors, and biological mechanisms are directly associated with physical function and likely contribute to age-related mobility and functional decline.

    “we have provided an overview of specific health conditions, behavioral factors, and biological mechanisms that have been directly linked with physical function, and therefore appear to play an important role in contributing to declines in mobility and physical function during aging.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Connected health has grown into a multi-billion market because Internet access and wellness devices are increasingly available.

    “Due to the increasingly widespread availability of Internet access and wellness devices, connected health has been flourishing into a multi-billion market. (Pai A 2014)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pai A 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The evidence now appears sufficient to move toward a consensus definition of successful aging markers in the physical domain.

    “Currently, there appears to be a sufficient body of evidence to move towards such a consensus definition on markers of successful aging within the physical domain.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A seamless design merges phase II and confirmatory phase III trials, improving efficiency by joint analysis and removing the gap between phases.

    “a seamless design combines the phase II trial and the confirmatory phase III trial, which improves efficiency through joint analysis of data and eliminates the gap between the two phases. (Wu, Wang, and Yang 2010)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wu, Wang, and Yang 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    An enrichment design seeks to cut trial costs by selecting a subpopulation likely to benefit most from treatment.

    “For example, an enrichment design attempts to reduce trial costs by targeting from the original heterogeneous study population a patient subpopulation that might optimally benefits from the treatment; (Wu, Tu, and He 2014)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wu, Tu, and He 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Big data in health care is driven mainly by high medical costs (17.9% of US GDP in 2012) and greater emphasis on evidence-based medicine.

    “Major factors driving this approach are the skyrocketing cost of medical care (17.9% of US GDP in 2012) and the increasing emphasis on evidence-based medicine. (Kayyali B, Knott D, and Van Kuiken S 2013)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kayyali B, Knott D, and Van Kuiken S 2013

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisenone given

    Without an accepted definition and agreed metrics, many different measures have been used to assess dimensions of successful aging.

    “First, in the absence of an accepted definition and commonly agreed on metrics, a diverse array of measures have been used to assess various dimensions of this construct.”
    Quote in the paperSubstantial claim
111 of 111

  • The paper relies on this without support.

    The physical functioning domain is where consensus on markers of successful aging is most developed.

    “The domain in which consensus on markers of successful aging is furthest developed is the domain of physical functioning.”
    “The strongest evidence of such markers can be found within the physical domain of the multidimensional construct of successful aging.”

  • The paper relies on this without support.

    Muscle tissue provides the body's only major reserve of readily available amino acids.

    “Moreover, muscle tissue provides the body’s only major “reserve” of readily available amino acids.”

  • The paper relies on this without support.

    Both humans and rodents show a steady increase in body weight and adiposity through early senescence followed by a decline in later life.

    “Both humans and rodents demonstrate a steady increase in body weight and adiposity through early senescence followed by a decline in later life.”

  • The paper relies on this without support.

    Leptin acts as a potent anorexic and energy-enhancing hormone in most young or lean animals, but its effects are diminished or absent in aged or obese states.

    “Leptin behaves as a potent anorexic and energy-enhancing hormone in most young or lean animals, but its effects are diminished or lacking in the aged or obese state.”

  • The paper relies on this without support.

    The mechanisms underlying age-related increases in pain and their contribution to functional decline remain poorly understood, and treatments for pain and pain-related disability in older adults are underdeveloped.

    “Despite the prevalence and adverse impact of pain among older adults, the mechanisms underlying age-related increases in pain and their contribution to functional decline remain poorly understood, and treatments designed to reduce pain and pain-related disability among older adults are woefully underdeveloped.”

  • The paper relies on this without support.

    The contribution of pain to the development of sarcopenia and/or dynapenia is not currently known.

    “Additionally, the contribution of pain to the development of sarcopenia and/or dynapenia is not currently known.”

  • The paper relies on this without support.

    Data on the importance of skeletal muscle in recovery from life-threatening situations such as severe burns or traumatic surgeries are limited.

    “While the contributions of sarcopenia to functional impairments are well documented, data regarding the importance of skeletal muscle in the recovery from life-threatening situations, such as severe burns or traumatic surgeries, are limited.”

  • The paper relies on this without support.

    Neither measurement of muscle mass nor muscle index is consistently associated with adverse outcomes.

    “In support of this, evidence suggests that neither the measurement of muscle mass nor muscle index (appendicular lean mass relative to BMI) is consistently associated with adverse outcomes.”

  • The paper relies on this without support.

    Dynapenia can be multifactorial, including deficits in muscle quality and neuromuscular control.

    “Rather, dynapenia can be multifactorial including deficits in muscle quality and neuromuscular control.”

  • The paper relies on this without support.

    Few therapies have been identified to improve functional performance in human aging.

    “Few therapies have been identified to improve functional performance in human aging, and there are currently no FDA-approved medications for the treatment of functional decline in older adults.”

  • The paper relies on this without support.

    There are currently no FDA-approved medications for the treatment of functional decline in older adults.

    “Few therapies have been identified to improve functional performance in human aging, and there are currently no FDA-approved medications for the treatment of functional decline in older adults.”

  • The paper relies on this without support.

    Low-grade chronic inflammation is a modifiable risk factor.

    “Low-grade chronic inflammation is a modifiable risk factor; however, it is unknown whether interventions that reduce the levels of inflammatory markers per se can improve mobility, or avert decline in mobility, in older adults.”

  • The paper relies on this without support.

    Long-term maintenance of lifestyle interventions can be difficult.

    “Long-term maintenance of lifestyle interventions can be difficult.”

  • The paper relies on this without support.

    Functioning levels are strongly interrelated across many domains, such as cognitive and physical function, in successful aging.

    “Given the strong inter-relationship of functioning level across many domains (e.g., cognitive and physical function) that comprise this construct”

  • The paper relies on this without support.

    Caloric restriction is the only known method that extends healthy lifespan across multiple species.

    “the only method to date that has been found to increase healthy lifespan in multiple species.”

  • The paper relies on this without support.

    It remains unknown whether resveratrol works in humans and through what mechanisms.

    “The critical question of whether resveratrol works in humans and by what mechanisms, however, has not been answered”

  • The paper relies on this without support.

    Only a few studies have examined resveratrol's effects in older adults.

    “and very few studies have examined the effects of resveratrol in older adults.”

  • The paper relies on this without support.

    No hormonal approach currently has conclusive evidence favoring it over another.

    “At present, there is not conclusive evidence to support one approach over another.”

  • The paper relies on this without support.

    Many adaptive designs can use accumulating data to modify a trial without compromising its validity or integrity.

    “Currently, many adaptive designs have been developed to use accumulating data to guide the subsequent modification of the study design without undermining the validity and integrity of the trial.”
19 of 19

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Accumulation of excess free radicals from the electron transfer chain, coupled with impaired detoxification of ROS, contributes to cumulative damage associated with aging, compromising mitochondria through protein oxidation and mtDNA mutations.

    “The accumulation of excess free radicals generated by the electron transfer chain, coupled with an impaired detoxification of ROS, contributes to cumulative damage associated with aging, ultimately compromising mitochondria through processes such as protein oxidation and mutations in mtDNA [67].”

    From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [67]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Resveratrol conflicts with the claim that caloric restriction is the only method

    Minor

    The paper says resveratrol extends healthy lifespan in several species, then calls caloric restriction the only method found to increase healthy lifespan in multiple species.

  • Two intervention subsections are numbered 2.4.5

    Minor

    The Exergaming and Non-Invasive Brain Stimulation subsections have the same section number.

2 of 2

Cites

1 retracted

Flagged first, then by citations

29 of the 490 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Baumgartner, 2000, Body composition in healthy aging, Ann. N. Y. Acad. Sci., 904, 437, 10.1111/j.1749-6632.2000.tb06498.x · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Anton, S. D., Woods, A. J., Ashizawa, T., Barb, D., Buford, T. W., Carter, C. S., Clark, D. J., Cohen, R. A., Corbett, D. B., Cruz-Almeida, Y., Dotson, V., Ebner, N., Efron, P. A., Fillingim, R. B., Foster, T. C., Gundermann, D. M., Joseph, A.-M., Karabetian, C., Leeuwenburgh, C., Manini, T. M., Marsiske, M., Mankowski, R. T., Mutchie, H. L., Perri, M. G., Ranka, S., Rashidi, P., Sandesara, B., Scarpace, P. J., Sibille, K. T., Solberg, L. M., Someya, S., Uphold, C., Wohlgemuth, S., Wu, S. S., & Pahor, M.
Affiliations
  • University of Florida Health (US)
  • University of Florida (US)
Corresponding author
Anton, Stephen D.
ORCID
Venue
Ageing Research Reviews
Publisher
Elsevier BV
Published
2015-11
Volume
24
Issue
Pt B
Pages
304-327
ISSN
1568-1637 (ISSN-L)
DOI
10.1016/j.arr.2015.09.005
PMC
PMC4661112
OpenAlex
W2213988996
Semantic Scholar
9f6a22223de572d9ca5f8f9eb86813c32a10df24
Cited by
292
References
490
Citations by year
2026: 15 · 2025: 26 · 2024: 37 · 2023: 37 · 2022: 36 · 2021: 36 · 2020: 31 · 2019: 24 · 2018: 9 · 2017: 26 · 2016: 14 · 2015: 1
FWCI
3.04
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Ageing Research Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Florida’s Claude D. Pepper Older Americans Independence Center (NIH/NIA P30AG028740)
  • Clinical and Translational Science Institute (NIH/NCRR UL1TR000064)
Topics
  • Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Balance, Gait, and Falls Prevention
  • Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
  • Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
Keywords
successful aging, physical independence, older adults, physical function, walking speed, mobility decline, behavioral factors, biological mechanisms, aging
MeSH terms
Activities of Daily Living, Adult, Aging, Humans, Health Behavior, Exercise, Physical Conditioning, Human

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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