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

Abstract

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.

Cognitive Deficits in Aging Related to Changes in Basal Forebrain Neuronal Activity

“…Although aging is not the cause of many neurodegenerative diseases, it can aggravate them because of cellular senescence. Cellular senescence can occur at any life stage, from embryo to adulthood, although it is associated with the aging process [133].…”

From regeneration to osteoarthritis in the knee joint: The role shift of cartilage-derived progenitor cells

“…Aged CPCs showed spontaneous osteogenic differentiation and lower chondrogenic differentiation (Chang et al, 2011). In our previously published data, sonic hedgehog, osteogenesis inducer, was highly expressed in OA-CPCs and could induce CPC senescence and chondrocyte apoptosis, which may be used as target and biomarkers for OA (Feng et al, 2021;Liu et al, 2022).…”

“…Recently, it is reported that overloading promotes chondrocyte senescence, and contributes to OA progression ( Zhang et al, 2022 ). However, physiological mechanical stimulation could upregulate chondrogenic markers in vitro ( Neumann et al, 2015 ), but nuclear factor kappa-B (NFκB) can abolish mechano-induced ECM synthesis ( Luckgen et al, 2022 ). In addition, mechanical loading is also associated with aging that younger animals showed greater plasticity ( Walsh et al, 2020 ).…”

Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals

“…Further, MSCs secretome releases several neurotrophic factors, which are all linked to axo-glial regeneration, such as neurotrophin-1 (NT-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT4), ciliary-derived neurotrophic factor (CDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor (bFGF), and ciliary neurotrophic factor (CNTF) [69]. However, recent studies show that cellular aging (i.e., donor age, increased passages, replication stress, telomere deletion, and cellular exhaustion) drives MSCs into senescence phenotype [70,71]. Resulting senescent MSCs are known to exhibit pro-inflammatory effects and impede tissue regeneration [70][71][72].…”

“…However, recent studies show that cellular aging (i.e., donor age, increased passages, replication stress, telomere deletion, and cellular exhaustion) drives MSCs into senescence phenotype [70,71]. Resulting senescent MSCs are known to exhibit pro-inflammatory effects and impede tissue regeneration [70][71][72].…”