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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 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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“dietary restriction (DR) increases lifespan or healthspan in all investigated eukaryote species, including unicellular and multicellular organisms of several distinct phyla, including non-human primates”
From The Hallmarks of Aging (2013) · cites this paper as Fontana et al., 2010
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Genetic polymorphisms or mutations that reduce the functions of GH, IGF-1 receptor, insulin receptor or downstream intracellular effectors such as AKT, mTOR and FOXO, have been linked to longevity, both in humans and in model organisms”
From The Hallmarks of Aging (2013) · cites this paper as Fontana et al., 2010
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Multiple genetic manipulations that attenuate signaling intensity at different levels of the IIS pathway consistently extend the lifespan of worms, flies and mice”
From The Hallmarks of Aging (2013) · cites this paper as Fontana et al., 2010
Experimental — accuracy not yet measured
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“Remarkably, the IIS pathway is the most conserved aging-controlling pathway in evolution”
From The Hallmarks of Aging (2013) · cites this paper as Fontana et al., 2010
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Collectively, current available evidence strongly supports the idea that anabolic signaling accelerates aging, and decreased nutrient signaling extends longevity”
From The Hallmarks of Aging (2013) · cites this paper as Fontana et al., 2010
The cited source says what the claim attributes to it.
In the citing paper
“Genetic analyses indicate that this pathway mediates part of the beneficial effects of DR on longevity in worms and flies”
From The Hallmarks of Aging (2013) · cites this paper as Fontana et al., 2010
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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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Metadata
- 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 (medical) › 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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