Towards Transferring the Cellular Benefits of Calorie Restriction

You might recall research involving parabiosis, in which researchers joined the circulatory systems of an old and a young mouse to measure the effects of signaling changes in the cellular environment that occur with age - and to see what the results would be if changes in the old environment were reversed. Prior investigations were conducted in cell cultures, exposing old cells to young blood or vice versa, which is how the fact that this resulted in interesting changes was noted in the first place.

Researchers here are walking down the same path with calorie restriction: it seems that changes are observed if you take blood serum from a calorie restricted individual and expose cells to it. This suggests that one component of the mechanisms by which calorie restriction extends life and improves health involves changes to the chemical makeup of the cellular environment, as one might expect:

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.



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