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<p>Circulating non-cellular factors, such as plasma proteins, contribute to various features of aging. To determine the impacts of endogenous circulating factors on human age-related bioenergetic decline, we treated primary human fibroblasts with serum samples representing the adult life-course. Our results demonstrate that the maximal mitochondrial bioenergetic capacity of fibroblasts treated with serum is negatively correlated with the chronological and epigenetic age of the serum donor. Using targeted proteomics, we identified plasma proteins associated with the bioenergetic effects of serum. We then utilized elastic net, a linear regression modeling technique, to derive a novel proteomic signature of age-related mitochondrial differences. MitoAge is a 25-protein signature of age-related mitochondrial health that predicts the systemic bioenergetic effects of circulating factors and is related to differences in physical function across human aging. Signatures that report on cellular hallmarks of aging, such as mitochondrial function, represent a new generation of mechanistically-informed biomarkers of biological aging.</p><p></p>

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The blood proteome predicts the impact of circulating factors on age-related mitochondrial health

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月24日

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  • Stephanie R. Heimler,
  • Jaclyn Bergstrom,
  • Nina S. Sun,
  • Toshiko Tanaka,
  • Ann Zenobia Moore,
  • Julián Candia,
  • Brian H. Chen,
  • Qu Tian,
  • Arsun Bektas,
  • Giovanna Fantoni,
  • Christopher Dunn,
  • Mary Kaileh,
  • Ranjan Sen,
  • Luigi Ferrucci,
  • Anthony J. A. Molina

摘要

Circulating non-cellular factors, such as plasma proteins, contribute to various features of aging. To determine the impacts of endogenous circulating factors on human age-related bioenergetic decline, we treated primary human fibroblasts with serum samples representing the adult life-course. Our results demonstrate that the maximal mitochondrial bioenergetic capacity of fibroblasts treated with serum is negatively correlated with the chronological and epigenetic age of the serum donor. Using targeted proteomics, we identified plasma proteins associated with the bioenergetic effects of serum. We then utilized elastic net, a linear regression modeling technique, to derive a novel proteomic signature of age-related mitochondrial differences. MitoAge is a 25-protein signature of age-related mitochondrial health that predicts the systemic bioenergetic effects of circulating factors and is related to differences in physical function across human aging. Signatures that report on cellular hallmarks of aging, such as mitochondrial function, represent a new generation of mechanistically-informed biomarkers of biological aging.