Nature agingJul 24, 2026

Long-term low valine intake improves health and lifespan differently in male and female mice

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 26, 2026

Abstract

Valine restriction increases median male lifespan by 23% in C57BL/6J mice.

Valine restriction improves metabolic health, promotes leanness, and enhances glycemic control in mice of all ages.
Reduced valine intake is linked to decreased frailty, lower cancer prevalence, and reduced senescent cell burden in both sexes.
A liver gene module associated with mitochondrial pathways is identified, showing increased mitochondrial respiration in male mice on valine restriction.
The findings suggest that dietary interventions mimicking valine restriction may have relevance for aging and age-related diseases.

Simplified

Dietary protein is a key regulator of metabolic health in humans and rodents. Many of the benefits of protein restriction are mediated by reduced intake of dietary branched-chain amino acids (leucine, valine and isoleucine) and restriction of the branched-chain amino acids is sufficient to extend healthspan and lifespan in mice. Here we find that valine restriction (Val-R) improves metabolic health in C57BL/6J mice, promotes leanness and glycemic control across ages, and reduces frailty, cancer prevalence and senescent cell burden in both sexes while increasing median male lifespan by 23%. Assessing gene relationships across tissues, we identified a liver gene module enriched in mitochondrial pathways and increased mitochondrial respiration in Val-R-fed male mice. Our results demonstrate that Val-R improves multiple aspects of healthspan in mice of both sexes, extends lifespan in male mice and suggests that interventions that mimic Val-R may have translational potential for aging and age-related diseases.