Nutrition

Blue Zones are regions reported to have unusually many centenarians. The popularly cited list (Buettner) includes Okinawa (Japan), Sardinia (Italy), Nicoya (Costa Rica), Ikaria (Greece), and Loma Linda (USA), while the demographically validated set typically comprises Sardinia, Okinawa, Nicoya, Ikaria, and sometimes Martinique. Shared features include plant-based diets, moderate caloric intake, low-intensity movement, strong social ties, and purpose. Saul Newman has argued that supercentenarian counts may be inflated by age-record errors, pension fraud, and missing birth registries.

Coenzyme Q10 (ubiquinone) is a lipid-soluble molecule essential for mitochondrial electron transport and ATP production, and an intracellular antioxidant. Endogenous levels decline with age and with statin use. Clinical evidence is strongest in heart failure, where supplementation is associated with reduced mortality and improved symptoms in some trials. Effects on blood pressure and statin-related muscle symptoms are modest; longevity benefits in healthy adults are not established.

Curcumin is the principal polyphenol in turmeric (Curcuma longa) and modulates NF-kB, Nrf2, and other inflammatory and oxidative pathways. Standard curcumin has very low oral bioavailability; supplements typically use piperine, phospholipid, or nanoparticle formulations. Meta-analyses suggest modest reductions in inflammatory markers, joint pain, and lipid measures, but effects vary by formulation and study quality. Evidence for direct longevity benefits in humans is limited.

EGCG is the most abundant catechin in green tea and a polyphenol with antioxidant, anti-inflammatory, and AMPK-modulating activity. Observational data link green tea consumption to lower cardiovascular and all-cause mortality. Trials of EGCG supplements show small effects on lipids, blood pressure, and body weight, with high-dose extracts associated with hepatotoxicity in rare cases. Direct evidence for human longevity from isolated EGCG remains limited.

Fisetin is a flavonoid found in strawberries, apples, and persimmons. In aged mice, Yousefzadeh et al. (2018) reported reduced senescent cell burden and extended median lifespan using a specific intermittent dosing protocol, though independent replication remains limited. Mechanisms include induction of apoptosis in senescent cells and modulation of inflammatory pathways, making it a candidate dietary senolytic under investigation. Human trials are ongoing, and clinical evidence in people remains preliminary.

The Mediterranean diet is an eating pattern emphasizing vegetables, fruits, legumes, whole grains, nuts, olive oil, and fish, with moderate dairy and limited red meat. Rich in monounsaturated fats, fiber, and polyphenols, it is associated with lower systemic inflammation, improved lipid profiles, and better endothelial function. Long-term adherence is associated in cohort studies and the PREDIMED trial (which tested Mediterranean diet supplemented with extra-virgin olive oil or mixed nuts; retracted and republished in 2018) with reduced cardiovascular events, type 2 diabetes risk, and all-cause mortality.

The MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) is a hybrid eating pattern targeting brain health. It emphasizes leafy greens, berries, nuts, whole grains, beans, fish, poultry, and olive oil while limiting red meat, butter, cheese, pastries, and fried food. Observational studies link higher adherence to slower cognitive decline and lower Alzheimer's incidence, though a 2023 randomized trial showed only modest cognitive effects over three years.

NMN is a nucleotide and NAD+ precursor in the salvage pathway, feeding into a coenzyme central to energy metabolism, sirtuin activity, and DNA repair. Oral NMN is absorbed and raises blood NAD+ in humans, but evidence for clinical longevity benefits remains limited. Trials report modest improvements on specific endpoints such as the 6-minute walk test, muscle insulin sensitivity, or grip strength; large, long-term outcome studies are lacking.

NR is a vitamin B3 form and NAD+ precursor that is metabolized via salvage pathways to increase NAD+, with NMN as a possible intermediate. Human trials reliably show that oral NR raises blood NAD+ and/or related metabolites and is well tolerated. Evidence for downstream clinical benefits, such as improved physical performance, metabolic health, or healthspan, is mixed and largely confined to small, short-duration studies.

Quercetin is a flavonoid abundant in onions, apples, capers, and berries with antioxidant and anti-inflammatory activity. It is investigated as a senolytic, though standalone activity is inconsistent in human cell models; the combination with dasatinib (D+Q) is the regimen actually studied in early human senolytic trials. Standalone supplementation has shown small, inconsistent blood pressure effects mainly in hypertensive populations, and bioavailability is low. Human anti-aging evidence is preliminary.

Resveratrol is a stilbene polyphenol found in grape skins, red wine, and Japanese knotweed. It is studied as a putative sirtuin (SIRT1) activator and AMPK modulator, with effects on inflammation and mitochondrial function in preclinical models. Human trials have produced inconsistent results, and oral bioavailability is poor. There is currently no robust evidence that resveratrol supplementation extends human lifespan or healthspan.

Spermidine is a naturally occurring polyamine found in wheat germ, aged cheese, soy, and mushrooms, though content varies widely by source and processing. It induces autophagy, the cellular recycling process implicated in aging, and extends lifespan in yeast, flies, and mice. In humans, dietary intake correlates with lower mortality in observational data; limited preliminary trials have explored possible cognitive signals, but results are not definitive. Causal effects on human longevity are not yet established.

Sulforaphane is an isothiocyanate generated when broccoli, broccoli sprouts, and other cruciferous vegetables are chewed or chopped. It activates the Nrf2 pathway, upregulating antioxidant and phase II detoxification enzymes. Human studies report effects on biomarkers of oxidative stress, inflammation, and cardiometabolic risk, with promising but mixed signals in autism and cancer chemoprevention. Long-term clinical outcomes from sulforaphane supplementation are not yet established.