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Serum from humans on long-term calorie restriction enhances stress resistance in cell culture.

ABSTRACT: 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.

SUBMITTER: Omodei D

PROVIDER: S-EPMC3796213 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Serum from humans on long-term calorie restriction enhances stress resistance in cell culture.

Omodei Daniela D Licastro Danilo D Salvatore Francesco F Crosby Seth D SD Fontana Luigi L

Aging 20130801 8

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 ...[more]

PMID: 23912304

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Project description:Background:Mathematical models have been developed to predict body weight (BW) and composition changes in response to lifestyle interventions, but these models have not been adequately validated over the long term. Objective:We compared mathematical models of human BW dynamics underlying 2 popular web-based weight-loss prediction tools, the National Institutes of Health Body Weight Planner (NIH BWP) and the Pennington Biomedical Research Center Weight Loss Predictor (PBRC WLP), with data from the 2-year Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study. Design:Mathematical models were initialized using baseline CALERIE data, and changes in body weight (?BW), fat mass (?FM), and energy expenditure (?EE) were simulated in response to time-varying changes in energy intake (?EI) objectively measured using the intake-balance method. No model parameters were adjusted from their previously published values. Results:The PBRC WLP model simulated an exaggerated early decrease in EE in response to calorie restriction, resulting in substantial underestimation of the observed mean (95% CI) BW losses by 3.8 (3.5, 4.2) kg. The NIH WLP simulations were much closer to the data, with an overall mean ?BW bias of -0.47 (-0.92, -0.015) kg. Linearized model analysis revealed that the main reason for the PBRC WLP model bias was a parameter value defining how spontaneous physical activity expenditure decreased with caloric restriction. Both models exhibited substantial variability in their ability to simulate individual results in response to calorie restriction. Monte Carlo simulations demonstrated that ?EI measurement uncertainties were a major contributor to the individual variability in NIH BWP model simulations. Conclusions:The NIH BWP outperformed the PBRC WLP and accurately simulated average weight-loss and energy balance dynamics in response to long-term calorie restriction. However, the substantial variability in the NIH BWP model predictions at the individual level suggests cautious interpretation of individual-level simulations. This trial was registered at clinicaltrials.gov as NCT00427193.

Dataset Information

Serum from humans on long-term calorie restriction enhances stress resistance in cell culture.

Publications

Serum from humans on long-term calorie restriction enhances stress resistance in cell culture.

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