Senescence-Associated Cell Transition and Interaction (SACTAI): A Proposed Mechanism for Tissue Aging, Repair, and Degeneration.

Aging is a broad process that occurs as a time-dependent functional decline and tissue degeneration in living organisms. On a smaller scale, aging also exists within organs, tissues, and cells. As the smallest functional unit in living organisms, cells "age" by reaching senescence where proliferation stops. Such cellular senescence is achieved through replicative stress, telomere erosion and stem cell exhaustion. It has been shown that cellular senescence is key to tissue degradation and cell death in aging-related diseases (ARD). However, senescent cells constitute only a small percentage of total cells in the body, and they are resistant to death during aging. This suggests that ARD may involve interaction of senescent cells with non-senescent cells, resulting in senescence-triggered death of non-senescent somatic cells and tissue degeneration in aging organs. Here, based on recent research evidence from our laboratory and others, we propose a mechanism-Senescence-Associated Cell Transition and Interaction (SACTAI)-to explain how cell heterogeneity arises during aging and how the interaction between somatic cells and senescent cells, some of which are derived from aging somatic cells, results in cell death and tissue degeneration.