Geroscience: Linking Aging to Chronic Disease
Open accessAbstract
Mammalian aging can be delayed with genetic, dietary, and pharmacologic approaches. Given that the elderly population is dramatically increasing and that aging is the greatest risk factor for a majority of chronic diseases driving both morbidity and mortality, it is critical to expand geroscience research directed at extending human healthspan.
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Chronological age is the main predictor of most diseases that cause most morbidity, mortality, and health costs in low-, middle-, and high-income countries.
“Chronological age is the major predictor for most of the diseases that account for the bulk of morbidity, mortality and health costs across low-, middle- and high-income countries2–7.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [3]
The Introduction calls aging the predominant risk factor for most diseases that limit healthspan, and the Aging Research Initiative describes chronic diseases as the majority of global disease burden and the most common causes of mortality. The paper also calls chronic diseases of aging a major global healthcare burden, but our copy does not establish the claim separately for low-, middle-, and high-income countries or explicitly identify chronological age as the predictor. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe Geroscience Hypothesis holds that the pillars of aging, including cellular senescence, tend to progress together and may be root-cause contributors to multiple diseases, age-related dysfunction, and loss of resilience.
“The Geroscience Hypothesis holds that these pillars of aging, including cellular senescence, tend to progress in concert and may be root-cause contributors to the pathophysiology of multiple diseases”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [3]
“The Pillars of Aging” section describes the seven pillars as highly intertwined processes that promote aging, and the introduction presents aging as a common driver of chronic disease. The paper also discusses cellular senescence and its potential adverse effects. It does not establish that the pillars progress together over time or that cellular senescence itself is a root-cause contributor to multiple diseases; no page numbers are available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredOld age is the strongest risk factor for the chronic diseases that account for most morbidity, mortality, and health-care costs globally.
“Old age is the greatest risk factor for the chronic diseases responsible for the majority of morbidity, mortality, and health-care costs worldwide (1, 2).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [1]
The Abstract calls aging the greatest risk factor for a majority of chronic diseases driving morbidity and mortality. The Aging Research Initiative says chronic diseases account for the majority of global disease burden and are the most common causes of mortality. It calls them a major global healthcare burden, but does not establish that they account for the majority of healthcare costs worldwide. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAnimal-model studies have provided support for the geroscience hypothesis.
“Recent studies of animal models have established the veracity of the geroscience hypothesis (1).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [1]
The Introduction reports that interventions extending lifespan in model organisms often delay or prevent chronic diseases, supporting the geroscience hypothesis. But the section on merging geroscience with human disease research cautions that mouse findings may not be validated in humans. Thus, the citing sentence’s claim that animal studies have “established the veracity” of the hypothesis is stronger than the source supports. (LLM, conf=0.84)
Experimental — accuracy not yet measuredInterlinked fundamental aging processes appear to act as root causes of many disorders and diseases.
“Interlinked and fundamental aging processes appear to be a root-cause contributor to many disorders and diseases.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [3]
The geroscience hypothesis proposes that treating fundamental aging mechanisms will affect multiple chronic diseases because those diseases share a common underlying mechanism.
“The recognition that old age is the greatest risk factor for most chronic diseases led to the geroscience hypothesis, which posits that therapeutically targeting fundamental aging mechanisms will successfully impact multiple chronic diseases because these diseases all share the same underlying mechanism (1).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [1]
The Geroscience Hypothesis posits that by targeting a fundamental ageing process such as cellular senescence, multiple age-related disorders can be delayed, prevented, or alleviated as a group, instead of one-at-a-time.
“This hypothesis posits that by targeting a fundamental ageing process such as cellular senescence, multiple age-related disorders can be delayed, prevented, or alleviated as a group, instead of one-at-a-time.”
DNA damage has far-reaching effects on many aspects of cellular metabolism tied to aging, the pillars of aging.
“The somewhat surprising finding is that DNA damage has far-reaching effects on many aspects of cellular metabolism tied to aging, the so-called pillars of aging (Kennedy et al., 2014).”
From DNA damage-how and why we age? (2021) · cites this paper as Kennedy et al., 2014
Senescent cells expressing the senescence-associated secretory phenotype promote multiple chronic conditions, including insulin resistance, cardiovascular disease, pulmonary arterial hypertension, chronic obstructive pulmonary disorder, emphysema, Alzheimer's and Parkinson's diseases, macular degeneration, osteoarthritis, and cancer.
“Senescent cells expressing this phenotype can in turn promote a multitude of chronic health conditions and diseases, including insulin resistance, CVD, pulmonary arterial hypertension, chronic obstructive pulmonary disorder, emphysema, Alzheimer’s and Parkinson’s diseases, macular degeneration, osteoarthritis and cancer54,55.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [55]
Accumulation of senescent cells in multiple tissues is a paramount mechanism that might account for inflammageing.
“Paramount among them is the accumulation of senescent cells in multiple tissues.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [87]
PA and exercise may be considered central geriatric care interventions that act on the cellular and molecular drivers of biological aging to decelerate the rates of aging.
“Thus, PA and exercise may be considered central geriatric care interventions, that is, interventions that act on the cellular and molecular drivers of biological aging to decelerate the rates of aging, which constitute the basics of the geroscience field [633,634].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [634]
PA and exercise may be considered central geriatric care interventions that act on cellular and molecular drivers of biological aging to decelerate rates of aging.
“Thus, PA and exercise may be considered central geriatric care interventions, that is, interventions that act on the cellular and molecular drivers of biological aging to decelerate the rates of aging, which constitute the basics of the geroscience field [633,634].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [634]
Hallmarks of aging are interconnected, and perturbation of one can affect others.
“The hallmarks of aging are interconnected (Kennedy et al., 2014; López-Otín et al., 2013; Zhang et al., 2015a), and age-associated perturbations of one can affect others.”
From The Aging Epigenome (2016) · cites this paper as Kennedy et al., 2014
Molecular and cellular decline of aging can be organized into evolutionarily conserved hallmarks.
“Over the past decades, a large body of research has shown that the molecular and cellular decline of aging can be organized into several evolutionarily conserved hallmarks or pillars of aging (Kennedy et al., 2014; López-Otín et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Kennedy et al., 2014
Time-dependent loss of autophagy proficiency critically contributes to the aged phenotype.
“time‐dependent loss of autophagy proficiency is thought to critically contribute to the aged phenotype (Lopez‐Otin et al, 2013; Kennedy et al, 2014; Lopez‐Otin & Kroemer, 2021)”
From Autophagy in major human diseases (2021) · cites this paper as Kennedy et al, 2014
Molecular causes of physical aging are thought to occur through accumulation of cellular damage to mitochondrial DNA, telomeric ends, coding-DNA, and proteins.
“The molecular causes of physical aging are thought to occur through the accumulation of cellular damage to mitochondrial DNA (mtDNA), telomeric ends, coding-DNA, and proteins (Kennedy et al, 2014).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Kennedy et al, 2014
Ageing is characterized by the appearance of chronic diseases such as sarcopenia, type 2 diabetes mellitus, cardiovascular disease, hypercholesterolemia, hypertension or neurodegenerative diseases.
“Ageing is also characterized by the appearance of different chronic diseases such as sarcopenia, type 2 diabetes mellitus (T2DM), cardiovascular disease, hypercholesterolemia, hypertension or neurodegenerative diseases among others (Kennedy et al., 2014).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Kennedy et al., 2014
Ageing is multifactorial involving genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intracellular communication.
“Ageing is multifactorial involving different molecular and cellular processes such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intracellular communication (Kennedy et al., 2014; Lopez-Otin et al., 2013).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Kennedy et al., 2014
Interventions that target key hallmarks of aging potentially can prevent, delay, or even reverse age-related conditions as a group.
“The geroscience hypothesis posits that interventions that target key hallmarks of aging potentially can prevent, delay, or even reverse age-related conditions as a group (1).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [1]
Biological ageing is enormously complex and is thought to be driven by the interaction of multiple dysregulated cellular and biochemical processes.
“Biological ageing is enormously complex and is thought to be driven by the interaction of multiple dysregulated cellular and biochemical processes3,4.”
From Measuring biological age using omics data (2022) · cites this paper as [3]
Much of the basic biology of ageing seems largely conserved among many species with very different lifespans.
“Indeed, it could be argued that, as much of the basic biology of ageing seems largely conserved among many species with very different lifespans3,4,8, clocks that measure a universal cause or rate of ageing should function ubiquitously.”
From Measuring biological age using omics data (2022) · cites this paper as [3]
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Self-citation
- Authors
- Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., Rando, T. A., Richardson, A., Schadt, E. E., Wyss-Coray, T., & Sierra, F.
- Affiliations
- Buck Institute for Research on Aging (US)
- University of Pennsylvania (US)
- Stanford University (US)
- University of California, San Francisco (US)
- Institute of Neurological Sciences (IT)
- Northwestern University (US)
- Albert Einstein College of Medicine (US)
- VA Palo Alto Health Care System (US)
- Oklahoma City VA Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- National Institutes of Health (US)
- Corresponding author
- Kennedy, Brian K.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 159
- Issue
- 4
- Pages
- 709-713
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4852871
- OpenAlex
- W2159914115
- Cited by
- 2,764
- References
- 15
- Citations by year
- 2026: 368 · 2025: 355 · 2024: 344 · 2023: 272 · 2022: 296 · 2021: 313 · 2020: 244 · 2019: 187 · 2018: 150 · 2017: 105 · 2016: 81 · 2015: 42 · 2014: 3
- FWCI
- 26.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG043080, R01AG033373, P01AG031782, R01AG024287, P01AG036695)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- geroscience, aging, chronic disease, healthspan extension, aging interventions, dietary intervention, older adults
- MeSH terms
- Aging, Animals, Chronic Disease, Humans, Biomedical Research, Epigenesis, Genetic, Gene-Environment Interaction
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