Extending Healthy Life Span—From Yeast to Humans
Open accessAbstract
Eat Less, Live Long: Studies in several model organisms have shown that dietary restriction without malnutrition, or manipulation of nutrient-sensing pathways through mutations or drugs, can increase life span and reduce age-related disease. Fontana et al. (p. 321 ) review the ways in which nutrient-sensing pathways are central to aging. Studies of yeast, worms, rodents, and primates show that these pathways are conserved during evolution. Although data on the effects of dietary restriction in primates are very limited, in humans, the protective effects of dietary restriction against cancer, cardiovascular disease, and diabetes must be judged against potentially negative long-term effects. More work is needed to determine whether dietary restriction and the modulation of anti-aging pathways through drugs can extend life span and reduce pathologies in humans.
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Caloric restriction is the most effective known way to extend healthspan and lifespan, and it works across species from yeast to primates.
“Caloric restriction has been demonstrated to be the most effective strategy to lengthen healthspan and lifespan, and is efficacious in a range of species from yeast to primates255.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [255]
The Introduction (page not provided) says dietary restriction extends average and/or maximum lifespan in species from yeast to rhesus monkeys and delays loss of function and major diseases in rodents and monkeys. The primate dietary-restriction section (page not provided) also reports fewer age-related deaths and diseases in restricted rhesus monkeys. The copy does not establish that caloric restriction is the most effective known strategy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDietary restriction has been the most effective strategy to demonstrate an increase in lifespan across a whole range of investigated species, including nonhuman primates.
“dietary restriction has been the most effective strategy to demonstrate an increase in lifespan across a whole range of investigated species, including nonhuman primates”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Fontana et al., 2010
The Introduction states that dietary restriction extends average and/or maximum lifespan in organisms ranging from yeast to rhesus monkeys. The primate dietary-restriction section also reports fewer age-related deaths in restricted rhesus monkeys. The paper does not establish the comparative claim that dietary restriction is the most effective lifespan-extending strategy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDietary, genetic, and pharmacological (rapamycin) inhibition of mTOR extends life span in multiple model organisms.
“Dietary, genetic, and pharmacological (rapamycin) inhibition of mTOR extends life span in multiple model organisms (83).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [83]
The IIS pathway informs cells of glucose levels and is the most conserved aging-controlling pathway in evolution.
“The IIS pathway informs cells of glucose levels and is the most conserved aging-controlling pathway in evolution.207”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [207]
Suppression of IIS dramatically extends lifespan in multiple organisms, suggesting an evolutionarily conserved mechanism.
“Suppression of the insulin–insulin-like growth factor 1 (IGF1) signalling (IIS) pathway dramatically extends lifespan in multiple organisms, which suggests that it is an evolutionarily conserved mechanism16.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [16]
Caloric restriction is the most consistent physiological intervention to improve health and extend lifespan across a wide range of organisms.
“Additional interest on how nutrient scarcity modulates mitochondrial function comes from the fact that CR is the most consistent physiological intervention to improve health and extend lifespan across a wide range of organisms (Fontana et al, 2010; Houtkooper et al, 2010b).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Fontana et al, 2010
The data infer the mutations cause a physiological state similar to that experienced during periods of reduced calorie intake.
“The data infer the mutations cause a physiological state similar to that experienced during periods of reduced calorie intake (206).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [206]
Caloric restriction reduces the generation of growth hormone, insulin, IGF1, and other growth factors, all of which have been shown to hasten aging and increase mortality in a number of species.
“Caloric restriction reduces the generation of growth hormone, insulin, IGF1, and other growth factors, all of which have been shown to hasten aging and increase mortality in a number of species (see Figure 3) (206).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [206]
Several genetic mutations, such as in the C. elegans DAF-16 transcription signaling pathway, involving nutrient-sensing pathways have been described and linked to a role in extending lifespan.
“Several genetic mutations, such as in the C. elegans DAF-16 transcription signaling pathway, involving nutrient-sensing pathways have been described and linked to a role in extending lifespan.”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [206]
Caloric restriction has been found to extend the life span of several organisms including S. cerevisiae, C. elegans, fish, rodents, and rhesus monkeys.
“Furthermore, caloric restriction has been found to extend the life span of several organisms including S. cerevisiae (yeast), C. elegans, fish, rodents, and rhesus monkeys (206, 207).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [206]
CR-mediated longevity in eukaryotes seems to be governed by a set of conserved nutrient signaling pathways.
“Importantly, CR-mediated longevity in eukaryotes seems to be governed by a set of conserved nutrient signaling pathways (Fontana et al., 2010).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fontana et al., 2010
Among these pathways are the insulin and the TOR/S6K pathways, whose inhibition upon CR eventually confers stress resistance and promotes survival during aging.
“Among them are the insulin and the TOR/S6K pathways, whose inhibition upon CR eventually confer stress resistance and promote survival during aging.”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fontana et al., 2010
CR has been shown to prolong mean and maximum lifespan in dogs, rodents, worms, flies, yeasts, and prokaryotes.
“Since then, CR has been shown to prolong mean and maximum lifespan in dogs, rodents, worms, flies, yeasts, and prokaryotes (Fontana et al., 2010).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fontana et al., 2010
CR reduces the release of growth factors like growth hormone, insulin and insulin-like growth factor 1 (IGF1), which have been shown to accelerate aging and increase mortality in many organisms.
“CR reduces the release of growth factors like growth hormone, insulin and insulin-like growth factor 1 (IGF1), which have been shown to accelerate aging and increase mortality in many organisms (Fontana et al., 2010).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fontana et al., 2010
Stress-related transcription factors represent the common effectors in yeast, flies, worms, and mammals.
“Stress-related transcription factors represent the common effectors in yeast, flies, worms, and mammals (Fontana et al., 2010).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fontana et al., 2010
Accumulating evidence suggests that protein restriction is necessary and sufficient for depletion of serum IGF1 in humans.
“Accumulating evidence suggests that protein restriction is necessary and sufficient for depletion of serum IGF1 in humans (Fontana et al., 2010).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fontana et al., 2010
Moderate CR may be harmful to lean human beings.
“Female rats subjected to prolonged CR become infertile in a reversible fashion (Martin et al., 2007), and moderate CR may be harmful to lean human beings (Fontana et al., 2010).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fontana et al., 2010
CR changes many parameters in the aging human body, including the transcriptome, the hormonal status (in particular the serum concentration of IGF-1 and thyroid hormones), oxidative stress, inflammation, mitochondrial function, and glucose homeostasis.
“CR changes many parameters in the aging human body, including the transcriptome, the hormonal status (in particular the serum concentration of IGF-1 and thyroid hormones), oxidative stress, inflammation, mitochondrial function, and glucose homeostasis (Fontana et al., 2010).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fontana et al., 2010
Exercise training can have a beneficial impact against diseases and metabolic disorders that typically accompany aging, notably cardiovascular diseases, diabetes and osteoporosis.
“Hence, exercise training can have a beneficial impact against diseases and metabolic disorders that typically accompany aging, notably cardiovascular diseases, diabetes and osteoporosis (Fontana et al., 2010).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fontana et al., 2010
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- Authors
- Fontana, L., Partridge, L., & Longo, V. D.
- Affiliations
- Washington University in St. Louis (US)
- University College London (GB)
- University of Southern California (US)
- Corresponding author
- Fontana, Luigi
- Partridge, Linda
- Longo, Valter D.
- Venue
- Science
- Published
- 2010-04-16
- Volume
- 328
- Issue
- 5976
- Pages
- 321-326
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3607354
- OpenAlex
- W2080094749
- Cited by
- 3,023
- References
- 75
- Citations by year
- 2026: 135 · 2025: 168 · 2024: 160 · 2023: 145 · 2022: 194 · 2021: 221 · 2020: 229 · 2019: 194 · 2018: 191 · 2017: 213 · 2016: 174 · 2015: 197 · 2014: 195 · 2013: 207 · 2012: 188
- FWCI
- 16.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Funders
- National Institute on Aging (AG20642, R01AG020642, AG025135, R01AG025135)
- National Institute of General Medical Sciences (R01GM075308, GM075308)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056341)
- National Center for Research Resources (UL1RR024992)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- dietary restriction, healthspan, aging, nutrient-sensing pathways, growth hormone receptor, age-related diseases, cancer, neurodegeneration, diabetes mellitus, rhesus monkeys, evolution of aging, healthy aging
- MeSH terms
- Aging, Animals, Haplorhini, Drosophila, Eating, Humans, Longevity, Saccharomyces cerevisiae, Signal Transduction, Caenorhabditis elegans, Caloric Restriction, Mice
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