Importance of circadian timing for aging and longevity.
Ontology highlight
ABSTRACT:
SUBMITTER: Acosta-Rodriguez VA
PROVIDER: S-EPMC8129076 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tissue specificity is a fundamental property of an organ that affects numerous biological processes, including aging and longevity, and is regulated by the circadian clock. However, the distinction between circadian-affected tissue specificity and other tissue specificities remains poorly understood. Here, using multi-omics data on circadian rhythms in mice, we discovered that approximately 35% of tissue-specific genes are directly affected by circadian regulation. These circadian-affected tissue-specific genes have higher expression levels and are associated with metabolism and hepatocyte cells. They also exhibit specific features in long-reads sequencing data. Notably, these genes are associated with aging and longevity at both the gene level and at the network module level. The expression of these genes oscillates in response to caloric and time-restricted feeding regimens, which have been demonstrated to promote longevity. In addition, aging and longevity genes are disrupted in various circadian disorders. Our study indicates that the modulation of circadian-affected tissue specificity is essential for understanding the circadian mechanisms that regulate aging and longevity at the genomic level.
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Project description:Background It has been suggested that migraine attacks strike according to circadian patterns and that this might be related to individual chronotype. Here we evaluated and correlated individual chronotypes, stability of the circadian rhythm, and circadian attack timing in a large and well-characterised migraine population. Methods In 2875 migraine patients and 200 non-headache controls we assessed differences in: (i) distribution of chronotypes (Münich Chronotype Questionnaire); (ii) the circadian rhythm's amplitude and stability (Circadian Type Inventory); and (iii) circadian timing of migraine attacks. Data were analysed using multinomial and linear regression models adjusted for age, gender, sleep quality and depression. Results Migraineurs more often showed an early chronotype compared with controls (48.9% versus 38.6%; adjusted odds ratio [OR]?=?2.42; 95% confidence interval [CI]?=?1.58-3.69; p?<?0.001); as well as a late chronotypes (37.7% versus 38.1%; adjusted OR?=?1.69; 95% CI?=?1.10-2.61; p?=?0.016). Migraineurs, particularly those with high attack frequency, were more tired after changes in circadian rhythm (i.e. more languid; p?<?0.001) and coped less well with being active at unusual hours (i.e. more rigid; p?<?0.001) than controls. Of 2389 migraineurs, 961 (40.2%) reported early morning attack onset. Conclusion Migraine patients are less prone to be of a normal chronotype than controls. They are more languid and more rigid when changes in circadian rhythm occur. Most migraine attacks begin in the early morning. These data suggest that chronobiological mechanisms play a role in migraine pathophysiology.
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Project description:Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and rare alleles, with impeccable control for population stratification and consideration of non-genetic factors such as environment.
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Project description:Circadian-affected tissue specificity is linked to aging and longevity
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Project description:Circadian rhythms, metabolism, and nutrition are intimately linked [1, 2], although effects of meal timing on the human circadian system are poorly understood. We investigated the effect of a 5-hr delay in meals on markers of the human master clock and multiple peripheral circadian rhythms. Ten healthy young men undertook a 13-day laboratory protocol. Three meals (breakfast, lunch, dinner) were given at 5-hr intervals, beginning either 0.5 (early) or 5.5 (late) hr after wake. Participants were acclimated to early meals and then switched to late meals for 6 days. After each meal schedule, participants' circadian rhythms were measured in a 37-hr constant routine that removes sleep and environmental rhythms while replacing meals with hourly isocaloric snacks. Meal timing did not alter actigraphic sleep parameters before circadian rhythm measurement. In constant routines, meal timing did not affect rhythms of subjective hunger and sleepiness, master clock markers (plasma melatonin and cortisol), plasma triglycerides, or clock gene expression in whole blood. Following late meals, however, plasma glucose rhythms were delayed by 5.69 ± 1.29 hr (p < 0.001), and average glucose concentration decreased by 0.27 ± 0.05 mM (p < 0.001). In adipose tissue, PER2 mRNA rhythms were delayed by 0.97 ± 0.29 hr (p < 0.01), indicating that human molecular clocks may be regulated by feeding time and could underpin plasma glucose changes. Timed meals therefore play a role in synchronizing peripheral circadian rhythms in humans and may have particular relevance for patients with circadian rhythm disorders, shift workers, and transmeridian travelers.
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