Aging attenuates the ovarian circadian rhythm

Abstract

Objective To study the effect of aging on ovarian circadian rhythm. Design Human and animal study. Setting University hospital and research laboratory. Patients/animals Human granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice. Intervention(s) None. Main outcome measure(s) Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice. Result(s) All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice. Conclusion(s) Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.

Circle(s) of Life: The Circadian Clock from Birth to Death

“…Downstream of the SCN, peripheral clocks are also disturbed in the elderly ( Figure 3 ). Transcriptional rhythms of multiple organs have been reported as attenuated in aged patients and mice, including ovaries [ 238 ], thyroid [ 239 ], skeletal and vascular muscle [ 240 ] and kidneys [ 241 ]. Some of those peripheral clock rhythms could potentially be restored by timed exercise [ 240 , 241 ].…”

“…Studies in mice show that voluntary wheel running can restore dysfunctions in activity rhythms in older mice, and there seems to be a sex difference in this response, as older females run significantly longer distances than males [ 242 ]. Surprisingly, some of these studies show a relative retention of liver rhythms [ 238 , 239 ], while another study conducted in rats suggest that changes in liver circadian genes during aging might be characteristic of males [ 243 ].…”

How Does Chronobiology Contribute to the Development of Diseases in Later Life

“… 53 Aging has a negative effect on mRNA levels of Bmal1, Clock, Per1 , and Per2 in mouse granulosa cells as the mRNA levels were decreased in older mice in comparison to younger. 14 , 54 Additionally, clock genes in the ovaries had shifts in rhythms with age. 54 Diurnal rhythms of Bmal1, Per1 , and Per2 were also dampened in the mouse heart.…”

“… 14 , 54 Additionally, clock genes in the ovaries had shifts in rhythms with age. 54 Diurnal rhythms of Bmal1, Per1 , and Per2 were also dampened in the mouse heart. 55 However, not all cells/organs have clock genes affected by aging.…”

Therapeutic potential of exosomes/miRNAs in polycystic ovary syndrome induced by the alteration of circadian rhythms

“…In addition, Per1 / Per2 double mutations mice have reduced ovarian follicular reserves, leading to a decline in fertility. ( 38 , 39 ) Studies have shown that BMAL1-KO mice exhibit abnormal follicle development, reduced fertilization rates, delays in early embryo/blastocyst developmental ( 40 , 41 ). Chen and colleagues found that down-regulation of BMAL1 expression inhibits the synthesis of progesterone and prostaglandin E2, which are key players in the reproductive process ( 42 ).…”