Journal Article

DZNE-2026-00824

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Beyond the hallmarks of aging: Rethinking what aging is and how we measure it

Keshavarz, M. (First author)DZNE* ; Ehninger, D. (Last author)DZNE*

2025

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Please use a persistent id in citations: doi:10.61373/gp025i.0119

Abstract: Aging is frequently assessed through lifespan extension and proxy biomarkers, yet these approaches may not fully capture the complexity of biological aging. Here, we propose refinements to discovery and evaluation strategies in aging research. Drawing on cross-species data, from humans to invertebrate models, we show mortality is often driven by a narrow set of life-limiting pathologies rather than a uniform systemic decline. This suggests lifespan extension can result from delayed disease onset without broadly slowing aging. Similarly, while tools like DNA methylation clocks and frailty indices offer value for stratification and prediction, their largely correlational nature limits mechanistic insight. Our systematic review exposes a key limitation in the widely cited “hallmarks of aging” framework: many supporting studies conflate baseline physiological shifts with genuine changes in aging rate. We advocate for study designs that enable differentiation of symptomatic effects from alterations to the trajectory of age-related phenotypic change. By integrating these refinements, the field can move toward a more mechanistic, nuanced understanding of aging, one that supports identifying causal regulators and developing interventions that truly modify aging trajectories.

Note: Missing Journal: Genomic Psychiatry () = 2997-2388 (import from CrossRef, Journals: pub.dzne.de)

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Contributing Institute(s):

1. Translational Biogerontology (AG Ehninger)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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