Figure 1.

Diagram representations of the Hayflick phenomenon. (A) Classic Hayflick model [5]. Phase I is the primary culture. Phase II is defined as the multiple cell passage period characterized by robust cell proliferation and increase of cell number. After subcultures of 40–60 passages, cells reach Phase III with halting proliferation followed by rapid cell death. Such an event is termed Hayflick Limit, or replicative senescence. (B) The SACTAI model. Phase I contains SomCs. During Phase II, cell passaging-induced cell proliferation triggers cell alteration. Some SomCs are converted into MSC and SnMSC due to replicative senescence. Cell proliferation is more than cell death in Phase II. The emergence of SnMSC results in its communication with SomC via SASP, which triggers catabolism and death of SomC. At the end of Phase II, cell proliferation equals death resulting in a cell number plateau. During Phase III, SASP triggered SomC death results in a rapid decline of total cell number. The loss of SomCs depletes the cell pool for proliferation. As a result, SnMSC triggered SomC cell death outpaces its proliferation, resulting in tissue degeneration. Thus, different cell types (SomC, MSC, and SnMSC) contribute to the cell transition and interaction during various phases. They account for aging-associated cellular changes. SomC: somatic cell; MSC: mesenchymal stromal cell; SnMSC: senescent mesenchymal stromal cell.