Longevity Papers 2025-12-14

A Fourfold Male-Specific Lifespan Extension via Canonical Insulin/IGF-1 Signaling (Russell et al., University of Alabama at Birmingham, December 5, 2025, BioRxiv, https://www.biorxiv.org/content/10.64898/2025.12.02.691904v1 ) - We explore how the daf-2 mutation extends male C. elegans lifespan by an extraordinary 4-fold with preserved healthspan, establishing sex as a primary determinant of longevity potential rather than a secondary variable. This challenges our understanding of insulin/IGF-1 signaling and suggests sex-specific interventions may be critical for anti-aging therapeutics. 2) Lifespan-extending downregulation of insulin signaling reduces germline mutation load (Duxbury et al., University of East Anglia, December 5, 2025, BioRxiv, https://www.biorxiv.org/content/10.64898/2025.12.05.692572v1 ) - We examine how reducing insulin/IGF-1 signaling in adulthood simultaneously extends somatic lifespan and reduces germline mutation rates by ~50 percent, dissolving the classical reproductive-somatic trade-off. The HRDE-1 epigenetic silencing pathway emerges as a novel mechanism linking nutrient sensing to genome stability across generations. 3) A Global Metabolomic and Lipidomic Landscape of Human Plasma Across the Lifespan (Liu et al., University of Science and Technology of China, December 6, 2025, Aging Cell, https://pubmed.ncbi.nlm.nih.gov/41351469/ ) - We discuss how untargeted metabolomics of 136 individuals reveals nonlinear metabolic trajectories with critical transition points, elevated amino acids and lipid dysbalance characterizing aging, and development of a clinically applicable plasma metabolite-based aging clock that may outperform epigenetic clocks for mortality prediction. 4) Genome-wide association study of proteomic aging reveals shared genetic architectures with longevity, early life development, and age-related diseases (Argentieri et al., Massachusetts General Hospital, December 4, 2025, MedRxiv, https://www.medrxiv.org/content/10.64898/2025.12.03.25341518v1 ) - We analyze 27 genetic loci associated with proteomic age gap showing strong genetic correlation with longevity (r=-0.83), with validated polygenic scores predicting increased odds of exceptional longevity and mechanistic links to FTO and m6A methylation-regulated metabolic aging. 5) Gut metabolism links precision nutrition, exercise, and healthspan in Drosophila melanogaster