Aging Effects on Cardiac Progenitor Cell Physiology

Abstract

Cardiac aging has been confounded by the concept that the heart is a postmitotic organ characterized by a predetermined number of myocytes, which is established at birth and largely preserved throughout life until death of the organ and organism. Based on this premise, the age of cardiac cells should coincide with that of the organism; at any given time, the heart would be composed of a homogeneous population of myocytes of identical age. The discovery that stem cells reside in the heart and generate cardiac cell lineages has imposed a reconsideration of the mechanisms implicated in the manifestations of the aging myopathy. The progressive alterations of terminally differentiated myocytes, and vascular smooth muscle cells and endothelial cells may represent an epiphenomenon dictated by aging effects on cardiac progenitor cells (CPCs). Changes in the properties of CPCs with time may involve loss of self-renewing capacity, increased symmetric division with formation of daughter committed cells, partial depletion of the primitive pool, biased differentiation to the fibroblast fate, impaired ability to migrate, and forced entry into an irreversible quiescent state. Telomere shortening is a major variable of cellular senescence and organ aging, and support the notion that CPCs with critically shortened or dysfunctional telomeres contribute to myocardial aging and chronic heart failure. These defects constitute the critical variables that define the aging myopathy in humans. Importantly, a compartment of functionally competent human CPCs persists in the decompensated heart pointing to stem cell therapy as a novel form of treatment for the aging myopathy.

Prolonged elevated levels of c‐kit+ progenitor cells after a myocardial infarction by beta 2 adrenergic receptor priming

“…In vitro sex-related biological responses | 18289 of human CPC have been described for TNF-α signaling (Straface et al, 2017). Age-related differences in CPC have also been reported (Rota, Goichberg, Anversa, & Leri, 2015). Our current study is limited with a focus on young male mice.…”

Decline in cellular function of aged mouse c‐kit+ cardiac progenitor cells

“…; Rota et al . ). Skeletal muscle stem cells in aged mice also have elevated expression of p16; this contributes to a switch from quiescent to senescent and their lack of activation upon injury (Sousa‐Victor et al .…”

“…This is in line with a previous study in which it was reported that CPCs isolated from 13-month FVBN mice presented flattened morphology and greater SA-β-Gal expression than a younger FVBN cohort . It has also been shown that p16 accumulates in various stem/progenitor cells including the brain, bone marrow, pancreas and heart in aged rodents (Krishnamurthy et al 2004;Torella et al 2004; Molofsky et al 2006;Rota et al 2015). Skeletal muscle stem cells in aged mice also have elevated expression of p16; this contributes to a switch from quiescent to senescent and their lack of activation upon injury (Sousa-Victor et al 2014).…”

“…Recently accumulated evidence suggests that the limited but documented cardiac repair observed with autologous therapy results from release of cytokines and growth factors from stem cells including CPCs (Torella et al 2004;Rota et al 2015;Khanabdali et al 2016). SDF-1, otherwise known as CXCL12, is a chemokine that mediates recruitment and trafficking of both haematopoietic and non-haematopoietic stem cells (Abbott et al 2004;Bromage et al 2014).…”

Influence of aging on the activity of mice Sca-1+CD31− cardiac stem cells

“…Sca-1 + cells in cardiac tissue may be the most common CSC/CPCs and be relatively easy to isolate [4], Sca-1 + CD31 − cells show cardiomyogenic differentiation and cell transplantation for myocardial repair [5, 6]. Changes in the properties of CSC/CPCs with age involving increased symmetric division, decreased cell proliferation and differentiation, loss of self-renewing capacity, partial depletion of the primitive pool, decreased expression of stem cell markers, impaired the migration ability, and changed the cell cycle into an irreversible quiescent state [7–9]. However, some other reports suggested that the impact of age on the quantity and quality of human cardiac stem cells is quite limited [10].…”