|
| CSCs and CDCs | |
| (i) Signs of senescence | |
| (a) Reduced telomere length | [80] |
| (b) Decreased telomerase activity |
| (c) Reduced expression of p16INKA and p21CIP |
| (d) Decreased expression of IL-6- and IGFBP7-enriched SASP |
| (e) Increased expression of the Wnt inhibitor Sfrp1and of p16 and a peculiar SASP typical in old subjects (65–83 years), differently from younger ones (2–65 years) | [81] |
| (ii) Known senescent triggers | |
| (a) Age-related cardiovascular pathologies, compromising heart function | [83–85] |
| (b) Antitumoral drugs, as anthracyclines | [82] |
| (c) Aged animals in physiological settings possess a remarkable number of cardiac stem cells, but dysfunctional in several biological activities, as the metabolism of vitamins and tyrosine, the circadian rhythm, and the complement and coagulation cascades. Consequently, cell proliferation, multipotency, and differentiation abilities are impaired | [86] |
| (d) Epigenetic modifications | [87] |
|
| HSC | |
| (i) Signs of senescence | |
| (a) Induced quiescence | [90–93] |
| (b) Overexpression of Mdr1 and Abcg2 transporters |
| (c) Glycolysis-mediated ATP generation |
| (d) Telomere shortening |
| (e) Accumulated mitochondrial mutations |
| (f) Reduced ROS production |
| (g) Reduced abilities of self-renewal and differentiation |
| (h) Although a high number of HSCs is retrieved in the elderly heart, these undergo a drastic lowering of clonal diversity and switch towards the myeloid lineage, consequently impairing their regenerative abilities | [94] |
|
| EPCs | |
| (i) Signs of senescence | |
| (a) Overexpressed angiotensin II | [95, 96] |
| (b) Increased induction of apoptosis |
| (c) Reduced levels of SDF-1 |
| (d) Intensified ROS production |
|
| MSCs | |
| (i) Signs of senescence | |
| (a) Classic senescent phenotype | |
| (b) Reduced migration capacity | [97] |
| (c) Decreased plasticity | |
| (d) Alterations in immunoregulatory abilities | [88, 98–100] |
|
