At the stem of youth and health.
Cellular senescence is a specialized form of growth arrest, confined to mitotic cells, induced by various stressful stimuli and characterized by a permanent growth arrest, resistance to apoptosis, an altered pattern of gene expression and the expression of some markers that are characteristic, although not exclusive, to the senescent state. Senescent cells profoundly modify neighboring and remote cells through the production of an altered secretome, eventually leading to inflammation, fibrosis and possibly growth of neoplastic cells. Mammalian aging has been defined as a reduction in the capacity to adequately maintain tissue homeostasis or to repair tissues after injury. Tissue homeostasis and regenerative capacity are nowadays considered to be related to the stem cell pool present in every tissue. For this reason, pathological and patho-physiological conditions characterized by altered tissue homeostasis and impaired regenerative capacity can be viewed as a consequence of the reduction in stem cell number and/or function. Last, cellular senescence is a double-edged sword, since it may inhibit the growth of transformed cells, preventing the occurrence of cancer, while it may facilitate growth of preneoplastic lesions in a paracrine fashion; therefore, interventions targeting this cell response to stress may have a profound impact on many age-related pathologies, ranging from cardiovascular disease to oncology. Aim of this review is to discuss both molecular mechanisms associated with stem cell senescence and interventions that may attenuate or reverse this process.
Interdepartmental Center for Regenerative Medicine (CIME), Department of Pathology, University of Udine, Italy. antonio.beltrami@uniud.it
Antonio Paolo
AP
Beltrami
Daniela
D
Cesselli
Carlo Alberto
CA
Beltrami
D000375:Aging / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D012060:Rejuvenation; D015398:Signal Transduction; D055153:Stem Cell Niche; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors