Time-dependent replicative senescence vs. disturbed flow-induced pre-mature aging in atherosclerosis

• Main Authors: Abishai Dominic, Priyanka Banerjee, Dale J. Hamilton, Nhat-Tu Le, Jun-ichi Abe
• Format: Article
• Language: English
• Published: Elsevier 2020-10-01
• Series: Redox Biology
• Subjects: Aging; Senescence; Atherosclerosis; Oxidative stress; Telomere shortening; Senescent-associated stemness
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213231720308193

Accumulation of senescent cells has a causative role in the pathology of age-related disorders including atherosclerosis (AS) and cardiovascular diseases (CVDs). However, the concept of senescence is now drastically changing, and the new concept of senescence-associated reprogramming/stemness has emerged, suggesting that senescence is not merely related to “cell cycle arrest” or halting various cellular functions. It is well known that disturbed flow (D-flow) accelerates pre-mature aging and plays a significant role in the development of AS. We will discuss in this review that pre-mature aging induced by D-flow is not comparable to time-dependent aging, particularly with a focus on the possible involvement of senescence-associated secretory phenotype (SASP) in senescence-associated reprogramming/stemness, or increasing cell numbers. We will also present our outlook of nicotinamide adenine dinucleotides (NAD)+ deficiency-induced mitochondrial reactive oxygen species (mtROS) in evoking SASP by activating DNA damage response (DDR). MtROS plays a key role in developing cross-talk between nuclear-mitochondria, SASP, and ultimately atherosclerosis formation. Although senescence induced by time and various stress factors is a classical concept, we wish that the readers will see the undergoing Copernican-like change in this concept, as well as to recognize the significant contrast between pre-mature aging induced by D-flow and time-dependent aging.