Growing scientific evidence indicates that intermittent fasting and calorie restriction can significantly prolong lifespan and reduce disease risk in animals. Researchers are now exploring ways to replicate the multi-system benefits of fasting through the use of targeted supplements. Two supplements in particular – resveratrol and NMN – appear to functionally mimic fasting at a molecular level by activating key pathways involved in longevity.
Resveratrol Primer
Resveratrol is a natural compound found in plant foods like grapes, peanuts, and berries. Early studies on resveratrol in yeast, flies, and mice seemed to prolong lifespan like calorie restriction or intermittent fasting. Further investigation revealed resveratrol activates longevity genes known as sirtuins.
Sirtuins are crucial enzymes involved in stress response, inflammation regulation, and genome maintenance. They require NAD+ as a coenzyme to function. Resveratrol was shown to activate sirtuins by indirectly stimulating NAD+ levels. Though a mild antioxidant, resveratrol’s main benefits come from directly controlling cellular defenses against aging at a genetic level.
When resveratrol was given alongside an every-other-day fasting schedule in mice, it further enhanced lifespan gains over either treatment alone. Resveratrol appeared to amplify natural responses to metabolic stress from fasting. Its sirtuin activation and gene expression changes offer the potential to mimic the multi-system effects of intermittent food restriction endogenously.
NMN Mechanism
The other supplement gaining prominence is nicotinamide mononucleotide, also known as NMN. NMN boosts levels of NAD+, the crucial cofactor sirtuins require. As we age, the body grows less efficient at NAD+ synthesis, correlating with declines in immune function and greater disease susceptibility.
Supplementing NMN has led to striking health impacts like improved cardiovascular fitness, reduced obesity, and extended lifespans in mice – similar to the effects of calorie restriction. Researchers hypothesize NMN supplementation may functionally mimic restriction diets by optimizing NAD+ signaling and sirtuin activation throughout the body.
In one 2018 study, six months of low-dose NMN treatment improved metabolic parameters reduced age-related myeloid-cell infiltration into fat tissues, and prevented weight gain in middle-aged mice. NMN treatment appeared to restore an expression pattern resembling that of younger animals.
Combined Benefits of Resveratrol and NMN
Experiments pairing resveratrol and NMN supplementation achieved even more impressive anti-aging results than either alone. Resveratrol acts as an accelerator stimulating sirtuin activity up to 500-fold, while NMN provides the necessary fuel to sustain this amplified response. Their combined mechanisms lead to more effective NAD+ level restoration and damage prevention.
A 2020 study gave aged mice resveratrol, NMN, or a combination daily for six months. Mice receiving both supplements showed significant gains in motor coordination and stamina, plus reduced visceral fat and liver inflammation compared to treatment with either compound alone. Their gene expression profiles also more closely matched those of healthier young mice.
Researchers concluded the combination treatment produced a “rejuvenating” effect by optimizing mitochondrial biogenesis and redox homeostasis, two processes vital for metabolic wellness but declining with age. While more research is needed, these preclinical findings support using resveratrol and NMN synergistically to functionally mimic the positive impacts of calorie restriction and fasting.
Additional Fasting Mimic Supplements
Beyond resveratrol and NMN, other compounds offer promise by targeting distinct pathways engaged during fasting periods. Some emerging candidates include:
- Berberine: Promotes glucose/lipid metabolism and displays anti-diabetic, anti-obesity properties. It may activate AMPK and mimic aspects of metabolic adaption to fasting.
- Metformin: Widely used diabetes drug that activates AMPK and represses mTOR signaling – two main response mechanisms to nutritional deprivation. Lowers cancer/dementia risks.
- Quercetin: Potent antioxidant that activates SIRT1 directly. Displays anti-inflammatory, and anticancer protection as well as glucose/lipid benefits like berberine.
- Urolithin A: A metabolite of ellagic acid found in pomegranates/walnuts. Induces mitophagy/autophagy – fasting-mimicking processes that clear unhealthy cells via lysosomal degradation.
- Fucoxanthin: Xanthophyll carotenoid from seaweed with anti-obesity effects via UCP1 induction. Also enhances mitohormesis, mitochondrial biogenesis in response to stressors.
Proper Dosing is Key
While early research holds promise, human application requires further study into optimal dosage regimens. Some supplements reduce cancer/heart disease risk, but higher doses may prove cytotoxic. Periodic rather than daily consumption aligns better with natural hormetic and fasting regimes. Diet/lifestyle factors also impact absorption.
Overall, endogenous approaches like calorie restriction, intermittent fasting, and judicious supplement use hold great potential not just to prolong quantity, but quality of life. Continued investigation of compounds can illuminate new longevity mechanisms and aid further innovation in healthy aging support therapies.
