Title : Replicative senescent human cells possess altered circadian clocks with a prolonged period and delayed peak-time

Authors : Rezwana Ahmed, Atsushige Ashimori, Satoshi Iwamoto, Takaaki Matsui, Yasukazu Nakahata, Yasumasa Bessho

Abstract : Over the last decade, a wide array of evidence has been accumulated that disruption of circadian clock is prone to cause age-related diseases and premature aging. On the other hand, aging has been identified as one of the risk factors linked to the alteration of circadian clock. These evidences suggest that the processes of aging and circadian clock feedback on each other at the animal level. However, at the cellular level, we recently revealed that the primary fibroblast cells derived from Bmal1-/- mouse embryo, in which circadian clock is completely disrupted, do not demonstrate the acceleration of cellular aging, i.e., cellular senescence. In addition, little is known about the impact of cellular senescence on circadian clock. In this study, we show for the first time that senescent cells possess a longer circadian period with delayed peak-time and that the variability in peak-time is wider in the senescent cells compared to their proliferative counterparts, indicating that senescent cells show alterations of circadian clock. We, furthermore, propose that investigation at cellular level is a powerful and useful approach to dissect molecular mechanisms of aging in the circadian clock.

Journal : AGING Volume : 11 Year : 2019 Issue : 3
Pages : 950-973 City : Edition : Editors :
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