“Glycolytic ATP production declines with age, contributing to common aging phenotypes such as reduced cell division and impaired DNA & mitochondria repair.”
BUFFALO, NY — March 3, 2026 — A new research perspective was published in Volume 18 of Aging-US on February 24, 2026, titled “ A decline in glycolytic ATP production is the fundamental mechanism limiting lifespan; species with an optimal rate of decline over time survived .”
Led by Akihiko Taguchi — who is also the corresponding author and is affiliated with the Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe — the perspective advances a unifying conceptual framework in which a programmed or selected decline in glycolytic ATP production over the lifespan underlies aging phenotypes across species. The authors argue that glycolysis supplies the rapid ATP required for cell division and DNA/mitochondrial repair, and that a progressive reduction in glycolytic ATP with age can explain reduced cell proliferation, impaired repair, and other hallmark features of aging.
“The simple explanation is that only species that happened to have an optimal rate of reduction in glycolytic ATP production over time were selected and survived through generational changes.”
The perspective synthesizes evidence from comparative biology, cellular metabolism, and translational studies to link glycolytic decline with lifespan variation among species — for example, contrasting short-lived rodents with long-lived species such as the naked mole rat, which maintain high glycolytic flux in low-oxygen niches. The authors also highlight mechanisms connecting glycolysis to mitophagy, telomere dynamics, and proteostasis, arguing that maintaining glycolytic ATP supports repair processes while a shift toward oxidative metabolism improves energy efficiency under resource limitation but reduces rapid-repair capacity.
The authors propose several concrete next steps to test the hypothesis. These include in vivo and in vitro interventions that modulate glycolysis (for example, gene transfer of glycolysis-related enzymes or pharmacologic activators such as terazosin), longitudinal measurements of glycolytic ATP production across aging cohorts, and comparative studies across species with differing lifespans to define the “optimal rate” of decline. They also suggest mechanistic studies of gap-junction–mediated metabolic coupling (for example, between hematopoietic stem cells and endothelium) and experiments to determine whether restoring glycolytic flux can rescue age-related deficits in DNA repair and tissue regeneration.
While the perspective offers a coherent conceptual model, the authors are explicit about limitations and caution: the idea is currently a hypothesis that requires experimental validation, and the evolutionary rationale (selection for an optimal rate of glycolytic decline) must be tested by comparative and mechanistic work. Translation to human rejuvenation therapies — whether via stem-cell approaches, metabolic activators, or gene transfer — will require careful preclinical studies to evaluate efficacy, safety, and long-term consequences.
Paper DOI : https://doi.org/10.18632/aging.206356
Corresponding author: Akihiko Taguchi – taguchi@fbri.org
Keywords: hypothesis, aging, glycolytic ATP production, lifespan, Heterocephalus glaber
Click here to sign up for free Altmetric alerts about this article.
______
To learn more about the journal, please visit www.Aging-US.com and connect with us on social media:
Click here to subscribe to Aging -US publication updates.
For media inquiries, please contact media@impactjournals.com .
Aging-US
News article
Not applicable
A decline in glycolytic ATP production is the fundamental mechanism limiting lifespan; species with an optimal rate of decline over time survived
24-Feb-2026
The authors declare that they have no conflicts of interest.