Telomeres shorten with each cell division eventually leading to replicative senescence
, a process thought to be associated with age-related decline in immune function.
However, MSC have a limited lifespan in vitro, exhibiting a progressive reduction in their capacity for self-renewal that usually ends in the irreversible arrest of cell division or replicative senescence
Cellular senescence resulting from repeated cellular replication is called "replicative senescence
" [13, 14].
Unlike cells with limited number of divisions, immortal cells do not undergo replicative senescence
. However, it was shown that they are prone to stress-induced senescence [71, 72].
This phenomenon, the "Hayflick limit" , also known as replicative senescence
, restricts the life span in vitro of all primary mammalian somatic cells.
However, as MSCs are expanded, they undergo replicative senescence
[15-17] and demonstrate morphological abnormalities, enlargement [18, 19], more podia and actin stress fibers [18, 20], less expression of specific surface markers, and decreased proliferation and differentiation [21-28].
was used as an in vitro surrogate for aging .
Several factors lead to senescence, and one of them is the cellular division, with telomere shortening, called replicative senescence
Epigenetic modifications leading to chronic inflammation have been described in ECs and immune cells of diabetes patients also in the absence of replicative senescence
biomarkers [23, 57, 58].
However, MSCs undergo replicative senescence
, limiting the number of divisions [39-41].
The cell senescence has indicated the irreversible G1 growth arrest of normal primary cells, which occurs after the cells have accumulated time-dependent damage, during extensive culture passages ("replicative senescence
Primary cultured cells undergo replicative senescence
, which is characterized by telomere shortening, genomic damage, epigenomic damage, and activation of tumor suppressors .