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Aged-senescent cells contribute to impaired heart regeneration.


Maximus Peto’s Commentary

This group note one concerning characteristic of cardiac progenitor cells in aged humans: “over half [of them] are senescent”. They report that clearing senescent cells with dasatinib and quercetin (in cell culture and in mice) reduces SASP and “activates” cardiac progenitor cells.


Aged-senescent cells contribute to impaired heart regeneration.
Aging Cell. 2019 Jun;18(3):e12931.
Lewis-McDougall FC, Ruchaya PJ, Domenjo-Vila E, Shin Teoh T, Prata L, Cottle BJ, Clark JE, Punjabi PP, Awad W, Torella D, Tchkonia T, Kirkland JL, Ellison-Hughes GM
DOI: 10.1111/acel.12931
PubMed publication date (edat): 3/12/2019

Abstract

Aging leads to increased cellular senescence and is associated with decreased potency of tissue-specific stem/progenitor cells. Here, we have done an extensive analysis of cardiac progenitor cells (CPCs) isolated from human subjects with cardiovascular disease, aged 32-86 years. In aged subjects (>70 years old), over half of CPCs are senescent (p16INK4A , SA-β-gal, DNA damage γH2AX, telomere length, senescence-associated secretory phenotype [SASP]), unable to replicate, differentiate, regenerate or restore cardiac function following transplantation into the infarcted heart. SASP factors secreted by senescent CPCs renders otherwise healthy CPCs to senescence. Elimination of senescent CPCs using senolytics abrogates the SASP and its debilitative effect in vitro. Global elimination of senescent cells in aged mice (INK-ATTAC or wild-type mice treated with D + Q senolytics) in vivo activates resident CPCs and increased the number of small Ki67-, EdU-positive cardiomyocytes. Therapeutic approaches that eliminate senescent cells may alleviate cardiac deterioration with aging and restore the regenerative capacity of the heart.

PMID: 30854802
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516154/

Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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