Of mice and men: the benefits of caloric restriction, exercise, and mimetics

Mercken, Evi M.; Carboneau, Bethany A.; Krzysik-Walker, Susan M.; de Cabo, Rafael

doi:10.1016/j.arr.2011.11.005

Cited by 318Genetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in MedicineDietary Effects on Health

Of mice and men: the benefits of caloric restriction, exercise, and mimetics

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Mercken, Evi M., Carboneau, Bethany A., Krzysik-Walker, Susan M., de Cabo, Rafael·2012·Ageing Research Reviews

DOI 10.1016/j.arr.2011.11.005PMC PMC3356510

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Abstract

During aging there is an increasing imbalance of energy intake and expenditure resulting in obesity, frailty, and metabolic disorders. For decades, research has shown that caloric restriction (CR) and exercise can postpone detrimental aspects of aging. These two interventions invoke a similar physiological signature involving pathways associated with stress responses and mitochondrial homeostasis. Nonetheless, CR is able to delay aging processes that result in an increase of both mean and maximum lifespan, whereas exercise primarily increases healthspan. Due to the strict dietary regime necessary to achieve the beneficial effects of CR, most studies to date have focused on rodents and non-human primates. As a consequence, there is vast interest in the development of compounds such as resveratrol, metformin and rapamycin that would activate the same metabolic- and stress-response pathways induced by these interventions without actually restricting caloric intake. Therefore the scope of this review is to (i) describe the benefits of CR and exercise in healthy individuals, (ii) discuss the role of these interventions in the diseased state, and (iii) examine some of the promising pharmacological alternatives such as CR- and exercise-mimetics.

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Caloric restriction extends lifespan in many organisms and decreases the burden of senescent cells.
“an intervention which has been shown to extend lifespan in a plethora of organisms and decrease the burden of senescent cells (Fontana et al., 2018; Mercken et al., 2012).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Mercken et al., 2012
Rapamycin and metformin can mimic effects of exercise and diet changes.
“There are also drugs, such as rapamycin and metformin, that are able to mimic the effects of exercise and diet changes (Mercken et al., 2012).”
From The Aging Epigenome (2016) · cites this paper as Mercken et al., 2012
Prolongevity CR mimetics such as rapamycin and metformin have been proposed to modulate mitochondrial dynamics in obesity and age-related diseases.
“Prolongevity CR mimetics such as rapamycin and metformin have also been proposed to modulate mitochondrial dynamics in obesity and age-related diseases (Mercken et al., 2012).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Mercken et al., 2012
Healthspan has not increased at the same pace as lifespan.
“The fact that healthspan has not increased at the same pace as lifespan is a source of grave concern (Mercken et al., 2012).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Mercken et al., 2012
A lower age-associated morbidity and a longer lifespan were observed among Spanish home nursing residents performing alternate day fasting, where residents fasted every other day with unrestricted food supply on the non-fasting day.
“A lower age-associated morbidity and a longer lifespan were observed among Spanish home nursing residents performing alternate day fasting, where residents fasted every other day with unrestricted food supply on the non-fasting day (Mercken et al., 2012).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Mercken et al., 2012

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Authors: Mercken, E. M., Carboneau, B. A., Krzysik-Walker, S. M., & de Cabo, R.
Affiliations: National Institutes of Health (US)
ORCID: Mercken, Evi M.
Venue: Ageing Research Reviews
Publisher: Elsevier BV
Published: 2012-07
Volume: 11
Issue: 3
Pages: 390-398
ISSN: 1568-1637 (ISSN-L)
DOI: 10.1016/j.arr.2011.11.005
PMC: PMC3356510
OpenAlex: W1974756058
Cited by: 318
References: 148
Citations by year: 2026: 21 · 2025: 12 · 2024: 11 · 2023: 17 · 2022: 14 · 2021: 19 · 2020: 17 · 2019: 19 · 2018: 27 · 2017: 29 · 2016: 28 · 2015: 31 · 2014: 31 · 2013: 32 · 2012: 10
FWCI: 2.35
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Ageing Research Reviews (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (ZIAAG000368, ZIAAG000363)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Health Sciences › Medicine › Physiology › Dietary Effects on Health
Keywords: caloric restriction, physical activity, aging, lifespan extension, healthspan, caloric restriction mimetics, exercise mimetics, resveratrol, metformin, rapamycin, mitochondrial homeostasis, stress response pathways, obesity, frailty, metabolic disorders, pharmacological interventions
MeSH terms: Aging, Animals, Energy Intake, Humans, Longevity, Metabolic Diseases, Exercise, Caloric Restriction, Biomimetic Materials, Mice

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Of mice and men: the benefits of caloric restriction, exercise, and mimetics

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