An ANGPTL8-AKT2-mTOR Axis Drives Adipose Senescence and Aging-Related Functional Decline

He Y, Pan L, Ping W, Meng C, Meng X, Guo Y, Kan R, Xiang Y, Mao B, Wang S, Li D, Yu X · 2026 · Aging Cell · Atlas ID HE2026

What this study shows

Identifies ANGPTL8 as an endocrine driver of adipose-tissue aging: circulating ANGPTL8 tracked with biological age and mortality risk in a large human cohort, and genetic deletion of Angptl8 in mice extended lifespan and reduced senescence markers. Mechanistically, ANGPTL8 binds AKT2 and drives the AKT-mTOR-S6K axis to promote adipocyte senescence; blocking that axis abolished the pro-senescent effect.

Abstract

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Adipose tissue senescence is increasingly recognized as a key driver of systemic aging and age-related functional decline, yet the endocrine regulators that actively promote this process remain poorly defined. Angiopoietin-like protein 8 (ANGPTL8) is a metabolic factor implicated in lipid metabolism and inflammation and has been associated with multiple aging-related disorders. However, its direct role in adipose tissue senescence and organismal aging remains unclear.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Human cohort (correlation) + mouse (Angptl8-/- knockout, lifespan) + primary adipocyte/cell studies); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Human cohort (correlation) + mouse (Angptl8-/- knockout, lifespan) + primary adipocyte/cell studies
Journal	Aging Cell
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1111/acel.70671 · PMID 42605193

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Angptl8 knockout (mouse lifespan); ANGPTL8 exposure with genetic or pharmacological AKT-mTOR-S6K inhibition in adipocytes; human cohort (observational)
Target	ANGPTL8-AKT2-mTOR-S6K axis
Model	Mouse; primary adipocytes; human cohort (correlative)
Effect	ANGPTL8 activates AKT-mTOR-S6K to promote adipocyte senescence; Angptl8 deletion extended mouse lifespan.

In the Atlas

Cite this paper

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He, Y., Pan, L., Ping, W., Meng, C., Meng, X., Guo, Y., Kan, R., Xiang, Y., Mao, B., Wang, S., Li, D., & Yu, X. (2026). An ANGPTL8-AKT2-mTOR Axis Drives Adipose Senescence and Aging-Related Functional Decline. Aging Cell. https://doi.org/10.1111/acel.70671

@article{HE2026,
  author       = {He, Y. and Pan, L. and Ping, W. and Meng, C. and Meng, X. and Guo, Y. and Kan, R. and Xiang, Y. and Mao, B. and Wang, S. and Li, D. and Yu, X.},
  title        = {{An ANGPTL8-AKT2-mTOR Axis Drives Adipose Senescence and Aging-Related Functional Decline}},
  journal      = {Aging Cell},
  year         = {2026},
  doi          = {10.1111/acel.70671},
  note         = {PMID: 42605193},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record HE2026) [Data set]. https://mtor-atlas.org/study/HE2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_HE2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record HE2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/HE2026/},
  doi          = {10.5281/zenodo.22059963}
}

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