In the pursuit of a longer, healthier life, scientists and health enthusiasts alike are turning their attention away from traditional markers of age, such as the number of birthday candles on a cake, and focusing on a more accurate measure—biological age. As acclaimed geneticist David Sinclair aptly puts it, “Biological age is a much better representation of health status than birthday candles. Birthday candles don’t tell you how well you’ve been living, and they certainly don’t tell you how many years you’ve got left.” In this blog, we explore three habits that have been proven to reverse biological age by a decade, providing insights into the keys to healthy aging.
1. Take Resveratrol
Some polyphenol treatments, including resveratrol, metformin, and rapamycin, mimic the effects of caloric restriction by interacting with longevity-related signaling pathways and molecules. Resveratrol activates proteins like Sirtuins and PGC1α, regulates the AMPK pathway, and reduces inflammation markers in humans and animals. Resveratrol supplementation can decrease markers of aging, including histone modifications, and activate FOXO3 independently of PI3K/AKT signaling. Overall, these polyphenols exhibit anti-inflammatory, antioxidant, and autophagy-promoting activities, contributing to positive aging-associated epigenetic changes.
2. Caloric Restriction
Eating fewer calories, known as caloric restriction (CR), by 10% to 40% without sacrificing nutrition has been proven to positively impact health and lifespan in various organisms, including humans. In places with longer lifespans, like Okinawa, Japan, lower calorie intake is linked to better health. CR triggers hormesis, an adaptive response to chemical or environmental exposure. At the cellular level, CR enhances DNA repair, delays neurodegeneration, improves glucose metabolism, reduces diabetes and cancer risks, and slows down epigenetic aging. CR is also connected to autophagy, promoted by nutrient depletion. Physiologically, CR influences nutrient-sensing pathways, lowering blood glucose, improving insulin sensitivity, and inhibiting pathways associated with cell growth. Weight loss from CR lowers the risk of age-related diseases, such as cardiovascular issues, and increases lifespan. The CALERIE 2 study on humans practicing 25% CR for two years showed improvements in quality of life, sleep, and sexual function.
3. Regular exercise
Physical exercise is a key strategy for achieving extended healthspan. Defined as any movement requiring energy expenditure, it has numerous benefits, including reducing frailty, improving cognition, and having neuroprotective effects. Physical activity positively impacts age-related conditions, inflammation (inflammaging), and immunosenescence. Despite limited understanding of the cellular and molecular mechanisms, studies link physical activity to bioactive lipids, genomic data, mitochondrial function, and the release of exercise-related molecules (exerkines). Epigenetically, regular exercise slows DNA methylation alterations associated with age and beneficially affects miRNAs regulating inflammation. Studies, including DNAm clocks like DNAmFitAge and DNAm GrimAge, show promising results in estimating healthy aging and lifespan, with a strong relationship to lifestyle factors, including physical activity. Consistent, varied intensity physical activity is more effective in impacting biological aging than purely occupational exercise, and exercises promoting relaxation, like yoga and meditation, decrease intrinsic epigenetic age acceleration. The World Health Organization advocates that ‘some exercise is better than nothing,’ emphasizing the importance of regular physical activity for overall health.
References:
Smith, A., & Minton, N. (2019). Resveratrol: A review of the anti-aging properties and mechanisms of action. Frontiers in Aging Neuroscience, 11, 294.
Rajado, Ana Teresa et al. “How can we modulate aging through nutrition and physical exercise? An epigenetic approach.” Aging vol. 15,8 (2023): 3191-3217. doi:10.18632/aging.204668 https://fortune.com/well/2023/07/06/harvard-genetics-professor-3-habits-reverse-biological-age-david-sinclair/
