Bone Marrow Rejuvenation

Abstract

Aging has been defined as “the sum of primary restrictions in regenerative mechanisms of multicellular organisms”.1 In other words, aging can also be described as a progressive functional decline; a gradual degeneration of physiological function; or the intrinsic, inevitable and irreversible time-related process of loss of viability and increase in disease vulnerability.2 As life expectancy rises, it has led to the rapid aging of populations. Aging is the key risk factor for major human chronic pathologies and has become a worldwide medical and social problem. The most common diseases of aging include Alzheimer's, arthritis, cancer, diabetes, depression and cardiovascular disorders. Certainly, increasing age is also an independent risk factor for the development of atherosclerosis and coronary artery disease.3, 4 Aging is accompanied by endothelial cell senescence and the progressive decline of endothelial function.5 Endothelial dysfunction primarily contributes to impeded re-endothelialization and exacerbated neointima formation upon vascular pathological lesions. Thus, recovery from the decline of endothelial function helps to prevent age-related vascular disease. With increasing age and persistent reactive oxygen species production, the capacity of adjacent endothelial cells to repair endothelial injuries is limited, and vascular recovery becomes dependent on the incorporation of circulating endothelial progenitor cells (EPCs).6 Bone marrow-derived circulating EPCs play a significant role in vascular re-endothelialization and suppression of neointima formation after vascular injury.7 These cells can be mobilized under the modulation of vascular endothelial growth factor (VEGF), matrix metallopeptidase-9 (MMP-9) and other factors to participate in repair of endothelial injury. Aging impairs EPC mobilization, migration and homing to sites of vascular injury (Fig. 1). Open in a separate window Figure 1 Age-related effects that impair the biological function of endothelial progenitor cells.