Calorie restriction is the most robust anti-aging and longevity-increasing treatment known, extending life up to 50% in laboratory animals. Humans likely will experience the same longevity benefits from calorie restriction, although intermittent fasting is easier to implement, but not enough humans have been restricting calories for a long enough time to have a definitive answer. But as the following paper shows, there’s something in the blood, or more specifically the serum, of humans who restrict calories that enhances stress resistance in cell cultures.
Calorie restriction (CR) without malnutrition is the most robust intervention to slow aging and extend healthy lifespan in experimental model organisms. Several metabolic and molecular adaptations have been hypothesized to play a role in mediating the anti-aging effects of CR, including enhanced stress resistance, reduced oxidative stress and several neuroendocrine modifications. However, little is known about the independent effect of circulating factors in modulating key molecular pathways. In this study, we used sera collected from individuals practicing long-term CR and from age- and sex-matched individuals on a typical US diet to culture human primary fibroblasts and assess the effects on gene expression and stress resistance. We show that treatment of cultured cells with CR sera caused increased expression of stress-response genes and enhanced tolerance to oxidants. Cells cultured in serum from CR individuals showed a 30% increase in resistance to H2O2 damage. Consistently, SOD2 and GPX1 mRNA, two key endogenous antioxidant enzymes, were increased by 2 and 2.5 folds respectively in cells cultured with CR sera. These cellular and molecular adaptations mirror some of the key effects of CR in animals, and further suggest that circulating factors contribute to the CR-mediated protection against oxidative stress and stress-response in humans as well.
Blood-borne factors that may cause an increase in stress resistance might include GDF-11, which is the factor thought responsible for the results in the mouse parabiosis experiments that have made such a splash. Control of aging as well as rejuvenation are systemic events, in other words, hormonally controlled.