Year: 2019
Type: article
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 (p16 INK4A , 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.
Source: Aging Cell
DOI: 10.1111/acel.12931
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,984
Awards: Defining the biology of human cardiac stem/progenitor cells for their use as an allogeneic cell therapeutic agent for myocardial repair & regeneration, Ageing and senescence of endogenous cardiac stem cells (eCSCs) determines myocardial regenerative potential, G3965397300, Effect of Aging on Preadipocyte Differentiation, G8805132569, G9000132058, Effect of Aging on Preadipocyte Differentiation
OpenAlex ID: W2922300104