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<p>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.</p>

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Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月24日

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  • Mariah F. Calubag,
  • Ismail Ademi,
  • Cara L. Green,
  • Dulmalika N. H. Manchanayake,
  • Hashan S. M. Jayarathne,
  • Ryan N. Marshall,
  • Sandra M. Le,
  • Penelope Lialios,
  • Lucia E. Breuer,
  • Shoshana Yakar,
  • Reji Babygirija,
  • Michelle M. Sonsalla,
  • Isaac Grunow,
  • Chung-Yang Yeh,
  • Yang Liu,
  • Bailey A. Knopf,
  • Sarah Yandell,
  • Charles I. Opara,
  • William A. Ricke,
  • Teresa T. Liu,
  • Mark P. Keller,
  • Alan D. Attie,
  • Marianna Sadagurski,
  • Dudley W. Lamming

摘要

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.