When a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging

Mihaylova, Maria M.; Chaix, Amandine; Delibegović, Mirela; Ramsey, Jon J.; Bass, Joseph; Melkani, Girish C.; Singh, Rajat; Chen, Jake Y.; Ja, William W.; Shirasu-Hiza, Mimi; Latimer, Mary N.; Mattison, Julie A.; Thalacker‐Mercer, Anna; Dixit, Vishwa Deep; Panda, Satchidananda; Lamming, Dudley W.

doi:10.1016/j.cmet.2023.06.008

Cited by 41 publications

(16 citation statements)

References 151 publications

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“…Common molecular mechanisms driving epigenetic alterations but leading to different epigenomes in cancer and noncancerous aged cells need further understanding, which is important to develop better therapeutic strategies, markers for early cancer detection and cancer-prevention approaches. Regarding the latter, recent developments in aging research have paved the way for the development of antiaging strategies, such as diet restriction, senolytics, and senomorphics, as potential interventions to address age-related disorders including cancer [126][127][128][129]. These antiaging approaches, aimed at targeting and mitigating multiple age-related processes like cellular senescence, inflammation, and metabolic imbalance, hold promise to revolutionize therapy of age-related diseases.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic dynamics of aging and cancer development: current concepts from studies mapping aging and cancer epigenomes

Bisht,

Mao,

Easwaran

2024

Current Opinion in Oncology

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Purpose of review This review emphasizes the role of epigenetic processes as incidental changes occurring during aging, which, in turn, promote the development of cancer. Recent findings Aging is a complex biological process associated with the progressive deterioration of normal physiological functions, making age a significant risk factor for various disorders, including cancer. The increasing longevity of the population has made cancer a global burden, as the risk of developing most cancers increases with age due to the cumulative effect of exposure to environmental carcinogens and DNA replication errors. The classical ‘somatic mutation theory’ of cancer cause is being challenged by the observation that multiple normal cells harbor cancer driver mutations without resulting in cancer. In this review, we discuss the role of age-associated epigenetic alterations, including DNA methylation, which occur across all cell types and tissues with advancing age. There is an increasing body of evidence linking these changes with cancer risk and prognosis. Summary A better understanding about the epigenetic changes acquired during aging is critical for comprehending the mechanisms leading to the age-associated increase in cancer and for developing novel therapeutic strategies for cancer treatment and prevention.

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Section: Discussionmentioning

confidence: 99%

Epigenetic dynamics of aging and cancer development: current concepts from studies mapping aging and cancer epigenomes

Bisht,

Mao,

Easwaran

2024

Current Opinion in Oncology

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“…In various organisms, from yeast to mammals, calorie restriction (with a significant reduction in food and caloric intake below ad libitum levels without causing malnutrition) has been found to be effective in increasing life span and delaying the onset of age-related diseases [13]. The molecular pathways underlying these benefits are complex and multifaceted, including reduced insulin and Insulin Growth Factor-1 (IGF-1) signaling, inhibiting the mechanistic target of rapamycin (mTOR) signaling, activation of AMP-activated protein kinase (AMPK) and sirtuins 1 (SIRT1), upregulation of the NAD+ pathway and autophagy, and reducing inflammation and oxidative stress [14,15]. However, the effects of sustained calorie restriction over the long-term in humans are much more challenging to study, especially in the context of the obesogenic food environment [16].…”

Section: Calorie Restriction and Energy Balancementioning

confidence: 99%

Diet strategies for promoting healthy aging and longevity: An epidemiological perspective

2023

J Intern Med

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In recent decades, global life expectancies have risen significantly, accompanied by a marked increase in chronic diseases and population aging. This narrative review aims to summarize recent findings on the dietary factors influencing chronic diseases and longevity, primarily from large cohort studies. First, maintaining a healthy weight throughout life is pivotal for healthy aging and longevity, mirroring the benefits of lifelong, moderate calorie restriction in today's obesogenic food environment. Second, the specific types or food sources of dietary fat, protein, and carbohydrates are more important in influencing chronic disease risk and mortality than their quantity. Third, some traditional diets (e.g., the Mediterranean, Nordic, and Okinawa) and contemporary dietary patterns, such as healthy plant‐based diet index, the DASH (dietary approaches to stop hypertension) diet, and alternate healthy eating index, have been associated with lower mortality and healthy longevity. These patterns share many common components (e.g., a predominance of nutrient‐rich plant foods; limited red and processed meats; culinary herbs and spices prevalent in global cuisines) while embracing distinct elements from different cultures. Fourth, combining a healthy diet with other lifestyle factors could extend disease‐free life expectancies by 8–10 years. While adhering to core principles of healthy diets, it is crucial to adapt dietary recommendations to individual preferences and cultures as well as nutritional needs of aging populations. Public health strategies should aim to create a healthier food environment where nutritious options are readily accessible, especially in public institutions and care facilities for the elderly. Although further mechanistic studies and human trials are needed to better understand molecular effects of diet on aging, there is a pressing need to establish and maintain long‐term cohorts studying diet and aging in culturally diverse populations.

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“…There is a growing awareness among both scientists and the public that a calorie is not "just a calorie," and that calories from different macronutrient sources may have effects on metabolism and healthy aging that are not simply related to their energy content (22). For example, restriction of dietary protein or of methionine extends the lifespan of rodents (23)(24)(25)(26), and lifelong restriction of the three branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) extends lifespan and reduces frailty in male C57BL/6J mice (27).…”

Section: Restriction Of Isoleucine Quantitatively Increases Male Heal...mentioning

confidence: 99%

Quantification of healthspan in aging mice: Introducing FAMY and GRAIL

Lamming

2023

Preprint

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The population around the world is graying, and as many of these individuals will spend years suffering from the burdens of age associated diseases, understanding how to increase healthspan, defined as the period of life free from disease and disability, is an urgent priority of geroscience research. The lack of agreed-upon quantitative metrics for measuring healthspan in aging mice has slowed progress in identifying interventions that do not simply increase lifespan, but also healthspan. Here, we define FAMY (Frailty-Adjusted Mouse Years) and GRAIL (Gauging Robust Aging when Increasing Lifespan) as new summary statistics for quantifying healthspan in mice. FAMY is based entirely on a widely utilized clinical frailty index, while GRAIL incorporates frailty, widely utilized healthspan assays, and information about the hallmarks of aging. Both metrics are conceptually similar to quality-adjusted life years (QALY), a widely-utilized measure of disease burden in humans, and can be readily calculated from data acquired during longitudinal and cross-sectional studies of mouse aging. We find that interventions generally thought to promote health, including calorie restriction, robustly improve healthspan as measured by FAMY and GRAIL. Finally, we show that use of GRAIL provides new insights, and identify dietary restriction of protein or isoleucine as an intervention that promotes healthspan but not longevity in female HET3 mice. We suggest that the routine integration of these measures into studies of aging in mice will allow the identification and development of interventions that promote healthy aging even in the absence of increased lifespan.

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When a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging

Cited by 41 publications

References 151 publications

Epigenetic dynamics of aging and cancer development: current concepts from studies mapping aging and cancer epigenomes

Epigenetic dynamics of aging and cancer development: current concepts from studies mapping aging and cancer epigenomes

Diet strategies for promoting healthy aging and longevity: An epidemiological perspective

Quantification of healthspan in aging mice: Introducing FAMY and GRAIL

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