Promoting Health and Longevity through Diet: From Model Organisms to Humans
Open accessAbstract
Reduced food intake, avoiding malnutrition, can ameliorate aging and aging-associated diseases in invertebrate model organisms, rodents, primates, and humans. Recent findings indicate that meal timing is crucial, with both intermittent fasting and adjusted diurnal rhythm of feeding improving health and function, in the absence of changes in overall intake. Lowered intake of particular nutrients rather than of overall calories is also key, with protein and specific amino acids playing prominent roles. Nutritional modulation of the microbiome can also be important, and there are long-term, including inter-generational, effects of diet. The metabolic, molecular, and cellular mechanisms that mediate both improvement in health during aging to diet and genetic variation in the response to diet are being identified. These new findings are opening the way to specific dietary and pharmacological interventions to recapture the full potential benefits of dietary restriction, which humans can find difficult to maintain voluntarily.
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Long-lived animals including naked mole-rats, calorie-restricted/intermittent-fasting rodents, and long-lived daf-2 mutant worms have decreased oxidative damage and greater resistance to oxidative stress.
“Accordingly, long-lived animals, including the naked mole-rat, rodents maintained on calorie restricted (CR) and intermittent fasting (IF) diets, and long-lived daf-2 mutant worms exhibit decreased levels of oxidative damage and are more resistant to oxidative stress (Fontana and Partridge, 2015; Guarente and Kenyon, 2000; Pérez et al., 2009).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Fontana and Partridge, 2015
Exercise and dietary changes including caloric restriction and intermittent fasting can slow and even reverse aging progression.
“Exercise and dietary changes, including caloric restriction and intermittent fasting, can slow and even reverse the progression of aging (Brandhorst et al., 2015; Fontana and Partridge, 2015; Garatachea et al., 2015; Mercken et al., 2012)”
From The Aging Epigenome (2016) · cites this paper as Fontana and Partridge, 2015
Effects of caloric restriction can be long lasting and passed to next generation.
“The effects of caloric restriction can be long lasting and even be passed on to the next generation (Fontana and Partridge, 2015).”
From The Aging Epigenome (2016) · cites this paper as Fontana and Partridge, 2015
Diet and exercise changes affect insulin/IGF signaling and AMPK and alter expression of many genes.
“Changes in diet and exercise impact the activity of various longevity regulatory mechanisms, including insulin/IGF signaling and the nutrient-sensing kinase AMPK, and can alter the expression of many genes (Fontana and Partridge, 2015; Garatachea et al., 2015).”
From The Aging Epigenome (2016) · cites this paper as Fontana and Partridge, 2015
Initiation timing and duration of metabolic interventions can alter their effect on longevity, indicating context matters and they are not one-size-fits-all.
“the initiation timing and duration of these metabolic interventions (exercise and diet changes) can alter their effect on longevity, suggesting that context is an important factor and that these are not “one size fits all” interventions (Fontana and Partridge, 2015).”
From The Aging Epigenome (2016) · cites this paper as Fontana and Partridge, 2015
Accumulating data from epidemiological, human clinical trials, animal, and molecular studies indicate that diet remains a key factor in the prevention of cardiovascular disease, obesity, type 2 diabetes, and some of the most common types of cancer.
“However, accumulating data from a combination of epidemiological, human clinical trials, animal and molecular studies indicate that diet remains a key factor in the prevention of cardiovascular disease, obesity, type 2 diabetes and some of the most common types of cancer (6).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [6]
Both the quantity and quality of what we eat is essential to promote metabolic and molecular health.
“Both the quantity and quality of what we eat is essential to promote metabolic and molecular health (6).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [6]
Caloric restriction is considered the most robust intervention to increase longevity in animal model systems and ameliorate age-associated disease in primates and humans.
“Additionally, CR is considered the most robust intervention to increase longevity in animal model systems and ameliorate age-associated disease in primates and humans (see “Prolonged fasting and caloric/dietary restriction” and “Aging”) (38).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [38]
Dietary restrictions increase lifespan and healthspan in all animal models of aging (yeast, C. elegans, Drosophila, mouse).
“Dietary restrictions have been shown to increase lifespan and healthspan in all animal models of aging (e.g., yeast, C. elegans, Drosophila, mouse) [239,289,290,291].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [289]
Similar to CR, IF improves multiple markers of health and increases longevity.
“Similar to CR, IF improves multiple markers of health and increases longevity (Fontana and Partridge, 2015).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Fontana and Partridge, 2015
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“Caloric restriction (CR) has been shown to increase lifespans and attenuate the harmful effects of aging across the evolutionary spectrum [1,2].”
BackgroundLu, Z.-G., Xie, J.-J., Wu, G., Shen, J.-H., Collins, R., Chen, W.-N., Kang, X., Luo, M., Zou, Y.-Z., Huang, L., et al. (2016) · Nature Medicine · doi:10.1038/nm.4252 · Cited by 124 · see citing works
- Authors
- Fontana, L., & Partridge, L.
- Affiliations
- Washington University in St. Louis (US)
- Max Planck Institute for Biology of Ageing (DE)
- Corresponding author
- Fontana, Luigi
- Partridge, Linda
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 161
- Issue
- 1
- Pages
- 106-118
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4547605
- OpenAlex
- W2096935190
- Cited by
- 1,245
- References
- 151
- Citations by year
- 2026: 65 · 2025: 98 · 2024: 99 · 2023: 94 · 2022: 121 · 2021: 158 · 2020: 141 · 2019: 130 · 2018: 121 · 2017: 91 · 2016: 94 · 2015: 33
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (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)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Wellcome Trust (098565)
- Bakewell Foundation
- European Commission
- Max-Planck-Gesellschaft
- National Institute on Aging
- 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, aging, longevity, intermittent fasting, meal timing, circadian feeding rhythm, protein restriction, amino acids, gut microbiota, age-related diseases, pharmacological interventions
- MeSH terms
- Aging, Animals, Diet, Health Promotion, Humans, Longevity, Models, Animal, Caloric Restriction
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