• 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2020-03
  • 2020-07
  • 2020-08
  • br VSMC senescence in age related diseases Aging as one


    VSMC senescence in age-related diseases Aging, as one of the most important risk factors for age-related diseases, is an inevitable process in life. As previously discussed, the number of senescent VSMCs increases with aging. To date, the methods used to characterize senescent Glpbio CCK-8 in vivo are limited. Studies have demonstrated that in contrast to diseases that are irrelevant to age, age-related diseases often occurred in the background of senescent cell accumulation and the subsequent chronic tissue/organ function loss [101]. Numerous studies have shown that VSMC senescence and age-related diseases are positively related. However, the causal relationship between them is not clear. Based on current evidence, cellular senescence in arteries, the consequences of which vary in different situations, seems to be harmful in age-related vascular diseases [11]. To differentiate whether cellular senescence is under the natural progression of aging (normal) or a condition of diseases (abnormal), Childs et al. [101] termed cellular senescence as primary senescence and secondary senescence. Primary senescent cells were based on ‘normal’ changes, which indicates this type of senescence was the fate of cells as the result of aging, tissue repair, etc. The secondary senescence seemed to be the ‘abnormal’ change as it occurred from the initiation of the diseases and continued through the entire course, which was in addition to the primary cellular senescence. Both primary senescence and secondary senescence could induce or aggravate age-related diseases. In this review, we focused on the current understanding of VSMC senescence in these age-related diseases: hypertension, atherosclerosis and diabetes.
    Future directions In the future, one question, which must be answered, is “does cellular senescence influence the individual health and lifespan?” As every coin has two sides, the effects of cellular senescence are double-sided. Senescent cells cannot undergo neoplastic transformation because of the disability of proliferation, making it an important safeguard of tumors [12]. However, senescent cells, particularly the SASP, may significantly increase inflammation in the local environment, resulting in more cells that become senescent. This long-term low-grade inflammation might be harmful in age-related diseases, such as hypertension, atherosclerosis, and diabetes [188]. With respect to VSMC senescence, current studies regarding antisenescent strategies have focused more on the endpoints, which were easy to measure, for example, the reduction of atherosclerosis [189] or the protection of arterial compliance [120]; in contrast, data regarding lifespan changes are scare. Based on the relationship between the proliferation potential of VSMCs and the donor age, it was calculated that the lifespan of human beings might be limited to less than 120 years [190]. It was also determined that VSMCs from Peromyscus leucopus, whose lifespan was twice that of Mus musculus, had approximately twice the proliferation activity than VSMCs from Mus musculus [191]. It was suspected that the decreased state of VSMC senescence might extend the lifespan. An animal study showed that the deletion of cardiotrophin 1 was able to decrease VSMC senescence and extend the lifespan of mice [124]. More studies, particularly studies in naturally aged animals, are required to identify the effects of the antisenescent therapies on aging, age-related diseases, health and the lifespan. Another question is “does prevention of cellular senescence by gene modification or drug treatment improve health or lifespan?” BubR1-insufficient mice displayed cellular senescence. Animal studies with BubR1-hypomorphic mice (a premature animal model) have shown that antisenescent treatment by CDKN2A deletion [192] or INK-ATTAC transgene [193] was able to extend the healthspan; however, it had no significant influence on the lifespan. It was also demonstrated that killing senescent cells with cytotoxic drugs in mice was able to improve the life quality and alleviate age-related chronic diseases in mice [194]. These findings provide clues related to the mystery of improving health or the lifespan via the prevention of cellular senescence.