A molecular index for biological age identified from the metabolome and senescence-associated secretome in humans.

Autor: Hamsanathan S; Aging Institute of UPMC and the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Anthonymuthu T; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Prosser D; Department of Medicine, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA., Lokshin A; Department of Medicine, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA., Greenspan SL; Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Resnick NM; Aging Institute of UPMC and the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Perera S; Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA., Okawa S; Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Narasimhan G; Bioinformatics Research Group (BioRG), School of Computing and Information Sciences, Biomolecular Sciences Institute, Florida International University, Miami, Florida, USA., Gurkar AU; Aging Institute of UPMC and the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Apr; Vol. 23 (4), pp. e14104. Date of Electronic Publication: 2024 Mar 07.
DOI: 10.1111/acel.14104
Abstrakt: Unlike chronological age, biological age is a strong indicator of health of an individual. However, the molecular fingerprint associated with biological age is ill-defined. To define a high-resolution signature of biological age, we analyzed metabolome, circulating senescence-associated secretome (SASP)/inflammation markers and the interaction between them, from a cohort of healthy and rapid agers. The balance between two fatty acid oxidation mechanisms, β-oxidation and ω-oxidation, associated with the extent of functional aging. Furthermore, a panel of 25 metabolites, Healthy Aging Metabolic (HAM) index, predicted healthy agers regardless of gender and race. HAM index was also validated in an independent cohort. Causal inference with machine learning implied three metabolites, β-cryptoxanthin, prolylhydroxyproline, and eicosenoylcarnitine as putative drivers of biological aging. Multiple SASP markers were also elevated in rapid agers. Together, our findings reveal that a network of metabolic pathways underlie biological aging, and the HAM index could serve as a predictor of phenotypic aging in humans.
(© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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