The cGAS-STING, p38 MAPK, and p53 pathways link genome instability to accelerated cellular senescence in ATM-deficient murine lung fibroblasts.

Majd Haj, Yann Frey, Amit Levon, Avishai Maliah, Tal Ben-Yishay, Rachel Slutsky, Riham Smoom, Yehuda Tzfati, Uri Ben-David, Carmit Levy, Ran Elkon, Yael Ziv, Yosef Shiloh

Department of Human Molecular Genetics and Biochemistry, Faculty of Health & Medical Sciences, Tel Aviv University, Tel Aviv 69978, Israel. · pubmed

Paper

Abstract

Ataxia-telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of the homeostatic protein kinase ATM. The complex phenotype of A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts from A-T patients exhibit premature senescence, highlighting the association between genome instability, cellular senescence, and aging. We found that lung fibroblasts derived from ATM-deficient mice provide a versatile experimental system to explore the mechanisms driving the premature senescence of primary fibroblasts lacking ATM.

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Research summary

The paper investigates the mechanisms linking genome instability to accelerated cellular senescence in ATM-deficient murine lung fibroblasts, which is relevant to understanding the biological processes underlying aging. While it provides solid research on a specific aspect of cellular senescence related to a genome instability syndrome, its findings are somewhat limited in scope and do not propose a direct solution to aging or lifespan extension. Thus, it represents a solid contribution but lacks broader implications for the field of longevity research.

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