Cellular senescence and its impact on the circadian clock

Abstract

Ageing is one of the greatest risk factors for chronic non-communicable diseases, and cellular senescence is one of the major causes of ageing and age-related diseases. The persistent presence of senescent cells in late life seems to cause disarray in a tissue-specific manner. Ageing disrupts the circadian clock system, which results in the development of many age-related diseases such as metabolic syndrome, cancer, cardiac diseases and sleep disorders and an increased susceptibility to infections. In this review, we first discuss cellular senescence and some of its basic characteristics and detrimental roles. Then, we discuss a relatively unexplored topic on the link between cellular senescence and the circadian clock and attempt to determine whether cellular senescence could be the underlying factor for circadian clock disruption.

Chronotherapy: Circadian Rhythms and Their Influence in Cancer Therapy

“…An individual’s circadian system is altered during aging and this is related to numerous age-associated pathologies such as metabolic syndrome, cancer, heart disease, neuronal diseases, and an elevated susceptibility to infections, among others [ 21 ]. The loss of diurnal rhythms of the immune response occurs during aging and is associated with a disappearance of clock genes transcription in aged macrophages and with smaller chromatin accessibility [ 22 ].…”

Emerging Insight Into the Role of Circadian Clock Gene BMAL1 in Cellular Senescence

“…Although ample evidence clearly demonstrated the role of the circadian clock in cellular senescence and aging- associated diseases, the precise molecular mechanisms of BMAL1 action in aging are a subject for further studies. Previous studies have identified that circadian proteins could be responsible for aging through the regulation of metabolism, genotoxic stress response and reactive oxygen species (ROS) homeostasis ( 12 , 36 ).…”

“…The amount of NAD+ is altered with the aging process and shows great linkage to circadian clock, which is attributed to posttranslational modifications of acetylation and poly-ADP-ribosylation status of circadian clock proteins and decreases with aging ( 86 ). And one recent study has pointed that NAD+ levels can be a potential mechanism that links the circadian clock with aging ( 12 ).…”

“…It has been reported that mice heterozygous for constitutively active p53 display an enhanced aging phenotype ( 156 ). Moreover, p53 is also under the regulation of circadian clock ( 12 ).…”

“…Many cellular and physiological activities are under the control of the circadian rhythm and there is emerging evidence that the circadian clock is intimately intertwined with the aging process ( 9 ). Besides, some studies also have pointed out that the circadian clock system is disrupted with aging ( 10 – 12 ). Alterations of the circadian clock have been reported in senescent cells ( 13 ) and stress-induced premature senescent cells ( 14 ), which showed a longer period and delayed phase compared to proliferative cells.…”