Abstract: ANGPTL8–AKT2–mTOR axis linked to adipose senescence in human cohorts and mice
In an abstract, circulating ANGPTL8 was associated with biological aging and mortality in a human cohort; in mice, deleting Angptl8 extended lifespan and reduced adipose senescence markers, and ANGPTL8 acted via AKT2–mTOR–S6K in cells. [1]
Automatic summary · not editorially reviewed
The key findings
In a large human cohort, circulating ANGPTL8 levels were strongly associated with biological aging and mortality risk. [1]
In mice, genetic deletion of Angptl8 extended lifespan and reduced senescence markers in adipose tissue. [1]
ANGPTL8 interacted with AKT2 and activated AKT-mTOR-S6K, promoting adipocyte senescence; inhibiting the pathway abolished these effects. [1]
The source at a glance
- Study type / format
- Abstract of integrative analyses: human cohort, animal models, transcriptomics and cellular studies.
- Population / context
- A large human cohort (size not reported in the abstract), mice and cellular studies.
- Summary based on
- Study abstract
- Original publication
- August 1, 2026
Human cohort links ANGPTL8 to biological aging
The abstract reports integrative analyses of human cohorts, animal models, transcriptomics and cellular studies. In a large human cohort, circulating ANGPTL8 levels were strongly associated with biological aging and mortality risk and significantly improved machine learning-based models for age and survival prediction. This is an association in observational human data, not evidence that ANGPTL8 causes aging or death in people.
Supporting source [1]
Mouse deletion extended lifespan; cells show AKT2–mTOR route
In mice, genetic deletion of Angptl8 extended lifespan, attenuated aging-associated functional decline and reduced senescence markers in adipose tissue. Transcriptomic analyses showed age-dependent upregulation of ANGPTL8 in adipocytes together with activation of pro-senescent transcriptional programs. Mechanistically, ANGPTL8 directly interacted with AKT2 and activated the AKT-mTOR-S6K signaling pathway, promoting cell-autonomous adipocyte senescence; genetic or pharmacological inhibition of this pathway abolished the pro-senescent effects of ANGPTL8. These are animal and cell findings, not demonstrated human lifespan benefits.
Supporting source [1]
Abstract names a potential target, not a proven therapy
The authors conclude that ANGPTL8 is an endocrine regulator linking metabolic dysfunction to adipose tissue senescence and systemic aging, and highlight the ANGPTL8-AKT2-mTOR axis as a potential therapeutic target for delaying age-associated functional decline. This is a proposed target from an abstract, not a validated treatment. The abstract does not report cohort size, follow-up duration, how biological aging was measured, or effect sizes.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Human findings are associations from a cohort of unreported size and follow-up. Lifespan and senescence-marker results come from mice, and mechanism from cellular studies; no human lifespan benefit is shown.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
He Y, Pan L, Ping W, Meng C, Meng X, Guo Y, Kan R, Xiang Y, Mao B, Wang S, Li D, Yu X. · europepmc.org · August 1, 2026