Calorie Restriction Reduces Biomarkers of Cellular Senescence in Humans

Overview

Journal Aging Cell

Specialties Cell Biology
Geriatrics

Date 2023 Nov 14

PMID 37961856

Authors

Zaira Aversa

Thomas A White

Amanda A Heeren

Cassondra A Hulshizer

Dominik Saul

Xu Zhang

Anthony J A Molina

Leanne M Redman

Corby K Martin

Susan B Racette

Kim M Huffman

Manjushri Bhapkar

Sundeep Khosla

Sai Krupa Das

Roger A Fielding

Elizabeth J Atkinson

Nathan K LeBrasseur

Affiliations

Soon will be listed here.

Abstract

Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change in HOMA-IR and insulin sensitivity index at 12 and 24 months, and the change in resting metabolic rate residual at 12 months. Finally, using adipose tissue RNA-sequencing data from a subset of participants, we observed a significant reduction in a senescence-focused gene set in response to CR at both 12 and 24 months compared to baseline. Our results advance the understanding of the effects of CR in humans and further support a link between cellular senescence and metabolic health.

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