Fasting, Time-Restricted Eating, Caloric Restriction & Longevity

Citation model. Claims grounded in AllNutrition's trust-scored library carry an inline bracketed reference [n] linking to the References section, which lists each source's evidence level and AllNutrition trust score (0–1). Where an AllNutrition query returned an overall evidence_strength and consensus_level, those labels are surfaced in the Evidence Review so readers can calibrate confidence. Only sources actually returned by the tool are cited; no trust scores are invented.

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1. Introduction

Few areas of nutrition science generate more public excitement — and more clinical overreach — than fasting and caloric restriction (CR) as tools for extending healthy lifespan. The underlying biology is genuinely compelling: a small set of evolutionarily conserved nutrient-sensing pathways (mTOR, AMPK, sirtuins, insulin/IGF-1 signaling) link food availability to cellular growth, repair, and survival programs, and manipulating these pathways through diet reliably extends lifespan in yeast, worms, flies, and rodents [2][21]. The seduction of this module is assuming that biology translates linearly to humans. It does not, at least not yet, and the central pedagogical task here is teaching students to hold two facts simultaneously: the mechanistic and animal evidence for nutrient-sensing-pathway modulation is deep and consistent, while the human outcome evidence — particularly for hard endpoints like mortality — remains thin, indirect, and in some domains actively contradicted by well-conducted trials and observational meta-analyses.

This module covers the biology of nutrient sensing, autophagy, and metabolic switching; the translation gap between animal caloric restriction studies and the human CALERIE trials; the proliferation of intermittent fasting (IF) modalities (alternate-day fasting, 5:2, time-restricted eating); the increasingly important finding that time-restricted eating (TRE) often performs no better than simple calorie-matched continuous restriction; fasting-mimicking diets; protein and methionine restriction; and the Blue Zones concept, presented with its methodological caveats rather than as settled fact. Throughout, the module models the appraisal discipline established in Module 1: distinguishing mechanism from outcome, animal data from human data, and surrogate markers from mortality.

2. Learning Objectives

By the end of this module, the learner will be able to:

1. Describe how mTOR, AMPK, sirtuins, and insulin/IGF-1 signaling integrate nutrient availability with cellular growth, autophagy, and stress-resistance programs, and explain the U-shaped relationship between IGF-1 and human mortality.
2. Explain the metabolic switch from glucose to fatty-acid/ketone-body metabolism during fasting, and characterize the strength of direct human evidence for fasting-induced autophagy versus animal/cell data.
3. Summarize the evidence for caloric restriction extending lifespan in rodents and non-human primates, and explain why the two major primate CR studies (University of Wisconsin and NIA) produced discrepant results.
4. Describe what the CALERIE-2 trial demonstrated about caloric restriction and human cardiometabolic risk and biological aging, and articulate why longevity/mortality benefit in humans remains unproven.
5. Differentiate the major intermittent fasting modalities (alternate-day fasting, 5:2, time-restricted eating, fasting-mimicking diets) and critically evaluate whether TRE produces benefits beyond calorie-matched continuous restriction.
6. Identify populations in whom fasting or CR is contraindicated or requires medical supervision (diabetes on insulin/sulfonylureas, pregnancy, eating disorder history, frailty/advanced age, being underweight), and counsel patients about the Blue Zones concept without overstating its evidentiary basis.

3. Scientific Foundations

3.1 Nutrient-sensing pathways: mTOR, AMPK, sirtuins, and IGF-1

Aging biology converges on a small number of interconnected nutrient-sensing networks that balance anabolism (growth) against catabolism (maintenance and repair) [26][21]. When nutrients are abundant, insulin and IGF-1 activate the PI3K-AKT-mTOR axis, promoting protein synthesis and cell growth while suppressing autophagy and inhibiting FoxO transcription factors that would otherwise drive stress resistance [26][21]. Downregulation of mTORC1 — via reduced protein and carbohydrate intake, rapamycin, or fasting — is one of the most consistent longevity-extending manipulations identified across model organisms [26][2].

AMPK functions as the cell's energy gauge, activated during energy scarcity (low ATP, fasting, exercise). Active AMPK inhibits mTOR, promotes autophagy, glucose uptake, fatty-acid oxidation, and mitochondrial biogenesis; AMPK sensitivity declines with age [26][21]. Sirtuins (SIRT1–SIRT7) are NAD⁺-dependent deacetylases activated during fasting and exercise as cellular NAD⁺ rises; SIRT1 promotes DNA repair and chromatin remodeling, and SIRT3 reduces mitochondrial oxidative stress. NAD⁺ and sirtuin activity decline with age [21].

Insulin/IGF-1 signaling (IIS) is the best-studied longevity pathway across species: mutations reducing IGF-1 signaling markedly extend lifespan in nematodes, and inhibiting IGF-1 receptor signaling in aging mice improves cardiac function and extends lifespan by relieving suppression of autophagy [26]. In humans, however, the relationship is not monotonic: IGF-1 shows a U-shaped association with mortality, with the lowest risk in an intermediate range (roughly 120–160 ng/mL); both very high and very low IGF-1 are associated with increased mortality [26]. This nonlinearity is a central teaching point — "lower IGF-1 is always better" is an oversimplification imported uncritically from invertebrate biology. Caloric restriction reliably lowers glucose, insulin, and IGF-1 in rodents, but CR in humans has not consistently lowered IGF-1; protein restriction specifically (rather than calorie restriction alone) appears to be the more reliable human lever for reducing IGF-1 [16][2].

3.2 Autophagy and the metabolic switch to ketone bodies

Autophagy — the lysosomal degradation and recycling of damaged proteins and organelles — is suppressed by mTOR/insulin signaling and induced by AMPK/sirtuin activation during fasting. The mechanistic case for autophagy as a driver of fasting's benefits is strong in cell and animal models: in mice, autophagy markers rise detectably in liver and brain tissue within 24–48 hours of food withdrawal [4].

Direct human evidence is more limited and largely restricted to peripheral blood mononuclear cells (PBMCs) rather than the organs of primary interest (brain, liver, muscle). Human trials have documented upregulation of autophagy-related genes (ATG5, BECN1/Beclin-1, ULK1, LC3B, LAMP2) and increased Beclin-1 protein after fasting protocols including Ramadan intermittent fasting and 30-day IF regimens, and one study found increased autophagic flux (not just static markers) in overweight individuals practicing isocaloric time-restricted feeding [19]. However, reviewers are explicit that it remains uncertain whether autophagy changes measured in blood cells reflect what is occurring in the brain, liver, or skeletal muscle, and that most human fasting trials are underpowered and short in duration relative to the tissue-specific, invasive methods used in animal work [19][20]. Autophagy in humans should therefore be taught as biologically plausible and partially confirmed at the gene/protein level in blood, not as a fully established mechanism of clinical benefit.

The metabolic switch — glucose to fatty-acid/ketone-body metabolism — is comparatively well characterized in humans. Liver glycogen depletes within roughly 24 hours; as insulin falls and glucagon rises, lipolysis releases free fatty acids that the liver converts to the ketone bodies acetoacetate, beta-hydroxybutyrate (BHB), and acetone once hepatic acetyl-CoA output exceeds TCA-cycle capacity [3][14]. This switch typically begins 12–36 hours into a fast and is substantially established by 48–72 hours, at which point the brain can derive up to ~60% of its energy from ketones, sparing muscle protein from gluconeogenic breakdown [4][3]. Beyond fuel provision, BHB functions as a signaling molecule that can suppress inflammation (via NLRP3 inflammasome inhibition), modulate sympathetic activity, and protect against oxidative stress [3]. Nutritional ketosis (ketones typically 0.5–7–8 mmol/L, stable pH) is physiologically distinct from diabetic ketoacidosis (ketones >15–25 mmol/L with acidosis), a distinction essential for patient counseling [3].

3.3 Caloric restriction in animal models: robust but not universal

Caloric restriction is the most reproducible lifespan-extending intervention in laboratory biology. Meta-analytic data across 145 rodent studies show a median lifespan increase of roughly 30% in rats and 15% in mice with 20–50% calorie reduction [2]. Mechanistically, CR reduces insulin, IGF-1, and growth-hormone signaling while activating AMPK and SIRT1 and suppressing mTOR [2][21]. Importantly, recent rodent work suggests that much of CR's benefit in mice may be attributable to the prolonged daily fast that results when animals rapidly consume a restricted ration, rather than to the calorie reduction per se — eliminating the fasting interval while holding calories constant blunts the longevity benefit [2][21]. This finding is a key bridge between the CR and fasting literatures and helps explain why intermittent fasting and time-restricted feeding are now studied as potential CR "mimetics."

The response is not universal: 40% CR increases mortality and impairs immunity in some mouse strains, and the benefit is highly dependent on genetic background, sex, and age of onset [2].

Non-human primate data are genuinely discordant. In rhesus macaques (~93% genetic homology to humans), the University of Wisconsin study reported a significant survival benefit from CR, while the NIA study found no significant survival advantage, though both found reduced incidence of age-related disease [2][21]. The leading explanations for the discrepancy are differences in diet composition (the UW control diet was higher in sucrose) and the fact that the NIA "ad libitum" control group was itself mildly food-restricted to prevent obesity, potentially masking the CR group's relative advantage [2]. This is one of the field's most instructive lessons in why translating animal longevity findings to humans is fraught even within closely related species.

3.4 Caloric restriction in humans: the CALERIE trials

CALERIE-2, a multi-center RCT, randomized healthy, non-obese adults (BMI 22.0–27.9) to ~25% targeted caloric restriction versus ad libitum eating for two years; participants achieved roughly 12% average restriction and lost approximately 7.5 kg [6][8]. Cardiometabolic outcomes improved significantly: reductions in total and LDL cholesterol, triglycerides, blood pressure, CRP, and TNF-α, with an increase in HDL [8]. Using multi-organ biological-age biomarkers, CR modestly slowed biological aging — by about 1.27 years whole-body, 1.00 year cardiovascular, and 0.63 years metabolic over the two-year intervention, with a dose-response relationship favoring participants who achieved ≥12.4% restriction [15]. Diet quality and nutritional adequacy were maintained through structured counseling and a daily multivitamin, and two years of moderate CR did not adversely affect iron status or anemia risk [6][7]. Adverse effects included reductions in bone mineral density and lean mass, arguing for concurrent resistance exercise [13][6].

What CALERIE-2 cannot show, by design, is an effect on mortality or maximum lifespan: it enrolled healthy, non-obese, middle-aged adults for two years, several orders of magnitude short of the timescale needed to observe a survival difference. The trial demonstrates that moderate CR is feasible without malnutrition and produces measurable, favorable changes in surrogate cardiometabolic and biological-aging markers — it does not demonstrate that CR extends human lifespan [13][15]. This surrogate-versus-hard-endpoint distinction, established in Module 1, is essential here.

4. Clinical Relevance

Patients arrive having read about fasting as a route to "activating autophagy," "resetting metabolism," or "living to 100 like the Blue Zones." Physicians need a calibrated response: CR and fasting produce real, reproducible improvements in weight, lipids, blood pressure, and inflammatory markers — clinically useful for cardiometabolic risk reduction — while the leap to "this will extend your lifespan" is not supported by direct human evidence and should not be promised. Clinicians also need working knowledge of who should not fast (insulin-treated diabetics, pregnant patients, those with eating-disorder histories, frail older adults) because these are exactly the populations most likely to encounter fasting advice from wellness media without medical context.

5. Evidence Review

Established (high confidence):

• Caloric restriction extends lifespan in rodents (median ~30% in rats, ~15% in mice) via reduced insulin/IGF-1/mTOR signaling and increased AMPK/SIRT1 activity. AllNutrition evidence_strength: limited, consensus_level: moderate (label reflects the tool's caution about extrapolating animal mechanism data, though the rodent lifespan finding itself is well-replicated) [2][21].
• CALERIE-2 (RCT) shows ~25%-targeted, 2-year caloric restriction in healthy non-obese adults improves lipids, blood pressure, inflammatory markers, and insulin sensitivity, with modest slowing of biological-aging biomarkers. AllNutrition evidence_strength: strong, consensus_level: moderate [6][8][15].
• Ketone-body metabolism during fasting (12–36 hour onset, brain utilization by 48–72 hours) is a well-characterized physiological pathway, mechanistically distinct from diabetic ketoacidosis [3][4].

Probable:

• Time-restricted eating produces weight loss largely comparable to matched continuous caloric restriction in RCTs; independent, calorie-independent metabolic benefits (e.g., insulin sensitivity in prediabetes, early-TRE circadian alignment) are plausible but not consistently demonstrated. AllNutrition evidence_strength: limited, consensus_level: moderate [9][3].
• Intermittent fasting is comparably effective to continuous caloric restriction for weight loss and short-term glycemic control in type 2 diabetes, but benefit largely disappears after discontinuation and requires medication adjustment to avoid hypoglycemia. AllNutrition evidence_strength: strong, consensus_level: moderate [17][12].
• Fasting-mimicking diets reduce cardiometabolic risk markers and IGF-1, and show adjunctive promise reducing chemotherapy toxicity, with generally low rates of severe adverse events in trials. AllNutrition evidence_strength: strong, consensus_level: moderate [11][5].

Emerging:

• Autophagy gene/protein upregulation (ATG5, BECN1, LC3B) has been directly measured in human blood following fasting protocols, but tissue-specific (brain, liver, muscle) autophagy in humans remains inferred from animal data rather than directly observed. AllNutrition evidence_strength: moderate, consensus_level: moderate [19][20].
• Protein and methionine restriction as a more targeted human lever for lowering IGF-1 than global calorie restriction, with strong rodent longevity data but only short-term human metabolic (not longevity) data [16][25].
• Pharmacological CR mimetics (rapamycin, metformin) targeting the same mTOR/AMPK pathways, with rapamycin the most robust lifespan-extending agent across model organisms but neither drug approved for human anti-aging use [21][20].

Controversial:

• Whether TRE confers cardiometabolic benefit beyond calorie restriction in real-world (as opposed to tightly controlled trial) settings: a systematic review and meta-analysis of observational studies found no significant association between TRE and abdominal obesity, metabolic syndrome, hypertension, dyslipidemia, or dysglycemia, contrasting with more favorable RCT findings, likely reflecting weight-loss dependence and diet-quality confounding outside controlled settings. AllNutrition evidence_strength: strong, consensus_level: moderate [22][9].
• The Blue Zones concept: population-level observations (plant-forward diets, caloric moderation, social structure) correlate with regional longevity, but critical reviews highlight ecological fallacy, survivor bias, genetic/cohort confounding, and inconsistent evidence on strict vegetarianism's mortality benefit. AllNutrition evidence_strength: moderate, consensus_level: mixed [23][24].
• A widely publicized observational signal linking very short (<8-hour) eating windows to higher cardiovascular mortality has circulated, but it derives from a conference-abstract-level analysis subject to substantial reverse-causation and dietary-recall limitations, and is not corroborated by the peer-reviewed observational meta-analysis identified here, which instead found no consistent association in either direction [22].

Unsupported / overstated:

• Extrapolating rodent or invertebrate lifespan-extension data from nutrient-sensing-pathway modulation directly onto human longevity claims, given the U-shaped IGF-1–mortality relationship in humans and the discordant primate CR trials [26][2].
• Treating CALERIE's biological-aging and cardiometabolic surrogate improvements as proof that caloric restriction extends human lifespan; the trial was neither designed nor powered for mortality endpoints [15][6].

6. Practical Clinical Applications

When fasting/TRE/CR may be appropriate:

• Adults with overweight/obesity and cardiometabolic risk factors seeking a structured, potentially more adherence-friendly alternative to daily calorie counting [9][3].
• As an adjunct to lifestyle counseling for prediabetes or early type 2 diabetes, with medical supervision and medication review [12][17].
• Combined with resistance training to preserve fat-free mass while reducing fat mass; meta-analytic and RCT data show IF/TRE plus resistance exercise attenuates or prevents the lean-mass loss seen with fasting alone, provided protein and total energy intake are adequate [16][18].

When to avoid or exercise caution:

• Diabetes on insulin or sulfonylureas — high hypoglycemia risk; requires self-monitoring 2–5×/day and proactive dose reduction under supervision (e.g., the INTERFAST-2 protocol) [12][17].
• Pregnancy — data are insufficient to recommend fasting for weight management; first-trimester fasting carries theoretical developmental risk (DOHaD framework), and prolonged Ramadan-style fasting is associated with dose-dependent neonatal hyperbilirubinemia; gestational diabetes management with fasting requires continuous glucose monitoring [10].
• History of eating disorders, dementia, or hormonal imbalance — planned restrictive eating cycles can exacerbate disordered eating and are not recommended in these groups [12][17].
• Frailty, advanced age, or risk of malnutrition/sarcopenia — protein intake below recommended levels in adults over 65 is associated with increased mortality and frailty, the inverse of the pattern in younger/middle-aged adults; CR and prolonged fasting are generally not recommended in frail older adults without careful nutritional and resistance-training support [25].
• Underweight individuals, children, and those with hormonal imbalances or immune deficiency — general contraindication across reviewed sources.

Practical counseling points: early time-restricted eating (window starting ≤8 a.m.) shows more consistent metabolic benefit than late TRE in trials; an 8–10 hour eating window balances feasibility and benefit; and patients should be told explicitly that TRE's benefit in free-living, real-world settings is less certain than in controlled trials.

7. Clinical Pearls

• "Fasting activates autophagy" is true at the gene/protein level in human blood — but tissue-specific human autophagy benefit is still inferred, not directly observed.
• CALERIE proved CR improves cardiometabolic surrogates and modestly slows biological-aging biomarkers in humans over two years; it did not and could not prove a lifespan benefit.
• TRE's real-world cardiometabolic benefit is far less certain than its trial-based benefit — counsel patients accordingly rather than treating meal-timing as a proven cardiovascular intervention.
• IGF-1 is not "the lower the better" in humans — it has a U-shaped mortality curve, unlike the simple linear relationship seen in invertebrate models.
• Any patient on insulin or a sulfonylurea who wants to try fasting needs a medication-adjustment plan before they start, not after a hypoglycemic episode.

8. Common Misconceptions

• "Animal caloric-restriction lifespan data means humans who restrict calories will live longer." Non-human primate CR trials were themselves discordant, and no human RCT has run long enough, or been powered, to test mortality [2][21].
• "Time-restricted eating works through a special metabolic mechanism, not just calorie reduction." Much of TRE's clinical-trial benefit appears attributable to spontaneous calorie reduction from the shortened window; head-to-head RCTs against calorie-matched continuous restriction generally show no significant additional benefit [9][22].
• "The Blue Zones prove that a specific diet extends human lifespan." The Blue Zones concept is an ecological, population-level framework vulnerable to ecological fallacy and survivor bias; it is a hypothesis-generating observation, not a validated causal dietary prescription [23][24].
• "Fasting is safe for everyone because it's natural." Fasting carries real, well-documented risks in diabetes (hypoglycemia), pregnancy, eating-disorder history, and frailty; "natural" is not synonymous with universally safe [10][17][25].

9. Summary

The biology connecting nutrient sensing (mTOR, AMPK, sirtuins, IGF-1) to aging is among the most reproducible findings in experimental gerontology, and caloric restriction is the most robust lifespan-extending intervention across simple model organisms and rodents. That robustness fades as organisms become more complex: non-human primate CR trials were discordant, and the best human evidence — the CALERIE-2 RCT — demonstrates clear, clinically meaningful cardiometabolic and biological-aging benefits from moderate caloric restriction without proving a mortality benefit, which was never within its power to show. Intermittent fasting and time-restricted eating are, for most people, roughly equivalent to matched continuous calorie restriction for weight and metabolic outcomes; the clinical value of TRE lies substantially in adherence and behavioral simplicity rather than in a unique circadian or autophagy-driven mechanism proven in free-living humans, where observational meta-analyses find no consistent cardiometabolic benefit at all. Autophagy and the glucose-to-ketone metabolic switch are real, partially confirmed human phenomena, but tissue-specific human autophagy benefit remains inferred rather than directly demonstrated. Fasting-mimicking diets and protein/methionine restriction offer more targeted, potentially safer routes to some of the same nutrient-sensing-pathway effects. Populations with diabetes on hypoglycemic agents, pregnant patients, those with eating-disorder histories, and frail older adults require specific caution or exclusion. The Blue Zones concept is a compelling hypothesis-generator, not proof of a longevity diet. The physician's task is to offer the genuine, evidence-supported cardiometabolic benefits of these strategies to appropriate patients while resisting the temptation — shared by patients and popular science alike — to promise longevity that the human data does not yet demonstrate.

10. References

Ordered by evidence strength / relevance. Evidence level and AllNutrition trust score (0–1) as returned by the tool.

1. Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing. The Journal of Physiology (2016). Review — trust 0.933.
2. Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms. Nutrients (2020). Review — trust 0.925.
3. The Effects of Intermittent Fasting on Brain and Cognitive Function. Nutrients (2021). Review — trust 0.9.
4. Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Nutrients (2019). Review — trust 0.9.
5. Gut Microbiota during Dietary Restrictions: New Insights in Non-Communicable Diseases. Microorganisms (2020). Review — trust 0.9.
6. Diet quality and nutritional adequacy during a 2-year calorie restriction intervention: the CALERIE 2 trial. American Journal of Clinical Nutrition (2025). RCT — trust 0.868.
7. Effect of 2-Year Caloric Restriction in the Absence of Malnutrition on Indicators of Anemia, Iron Status, and Hepcidin in Healthy Adults: A Randomized Clinical Trial. The Journal of Nutrition (2026). RCT — trust 0.853.
8. Effects of Caloric Restriction Diet on Arterial Hypertension and Endothelial Dysfunction. Nutrients (2021). Review — trust 0.85.
9. Does Timing Matter? A Narrative Review of Intermittent Fasting Variants and Their Effects on Bodyweight and Body Composition. Nutrients (2022). Review — trust 0.85.
10. Intermittent Fasting During Pregnancy and Neonatal Birth Weight: A Systematic Review and Meta-Analysis. Nutrients (2025). Systematic review — trust 0.842.
11. Fasting-mimicking diets as a strategy to reprogram tumor metabolism: a systematic review. European Journal of Nutrition (2026). Systematic review — trust 0.842.
12. Effects of intermittent fasting on HbA1c and weight in insulin versus oral hypoglycemic therapy-treated patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Frontiers in Nutrition (2026). Systematic review — trust 0.842.
13. Is Caloric Restriction Associated with Better Healthy Aging Outcomes? A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients (2020). Systematic review — trust 0.838.
14. Effects of Intermittent Fasting on Cardiometabolic Health: An Energy Metabolism Perspective. Nutrients (2022). Review — trust 0.838.
15. Effect of caloric restriction on organ-specific biological aging in a randomized clinical trial. Clinical Nutrition (2026). RCT — trust 0.832.
16. Time-restricted eating shows a modest reduction in fat mass in resistance-trained individuals: A systematic review and meta-analysis. Nutrition Research (2026). Systematic review — trust 0.827.
17. The metabolic effects of intermittent fasting in patients with type 2 diabetes exist in the short term but disappear after its discontinuation: A systematic review and meta-analysis of randomized controlled trials. Nutrition Research (2025). Systematic review — trust 0.817.
18. Impact of Intermittent Fasting and/or Caloric Restriction on Aging-Related Outcomes in Adults: A Scoping Review of Randomized Controlled Trials. Nutrients (2024). Review — trust 0.8.
19. Links Between Autophagy and Healthy Aging. Journal of Molecular Biology (2026). Review — trust 0.765.
20. A Critical Assessment of Fasting to Promote Metabolic Health and Longevity. Endocrine Reviews (2025). Review — trust 0.761.
21. When a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging. Cell Metabolism (2023). Review — trust 0.767.
22. The cross-sectional and prospective associations between time-restricted eating and cardiometabolic health in community-dwelling adults: A systematic review and meta-analysis of observational studies. European Journal of Clinical Nutrition (2026). Systematic review — trust 0.713.
23. How to become a centenarian in four weeks? Myths and limits of longevity recipes: a critical review. Minerva Medica (2026). Review — trust 0.688.
24. Vegetarian diets for longevity: friend or foe? Maturitas (2025). Review — trust 0.698.
25. The impacts of different dietary restriction regimens on aging and longevity: from yeast to humans. Journal of Biomedical Science (2025). Review — trust 0.705.
26. Insights into the therapeutic strategies for aging and aging-associated diseases. Signal Transduction and Targeted Therapy (2026). Review — trust 0.777.

Supporting sources also surfaced: NutrimiRAging: Micromanaging Nutrient Sensing Pathways through Nutrition to Promote Healthy Aging (Int J Mol Sci 2017, review, trust 0.838); Does eating less make you live longer and better? An update on calorie restriction (Clinical Interventions in Aging 2017, review, trust 0.75); The ups and downs of caloric restriction and fasting: from molecular effects to clinical application (EMBO Mol Med 2021, review, trust 0.728); Sex-Specific Responses to Intermittent Fasting (Nutrients 2026, review, trust 0.715); Concept and connotation of the geroprotective and anti-aging effects of metformin (Mol Cell Endocrinol 2026, review, trust 0.715); Methionine restriction in cancer: a dietary insight for therapy (Frontiers in Nutrition 2026, review, trust 0.73); Immunomodulatory effects of calorie restriction and its mimetics (Pharmacological Reviews 2025, review, trust 0.752); Chrononutrition and cardiometabolic health: circadian timing as a dimension of precision nutrition (Frontiers in Nutrition 2026, review, trust 0.762); Nutrition and longevity – diet in centenarians (J Transl Med 2026, review, trust 0.76); Efficacy of time restricted eating and resistance training on body composition and mood profiles (JISSN 2025, RCT, trust 0.81).