Chronobiology of Aging: A Mini-Review

Abstract

Aging is generally associated with weakening of the circadian system. The circadian amplitude is reduced and the circadian acrophase becomes more labile, tending to occur earlier with advancing age. As originally noted by Franz Halberg, similar features are observed in the experimental laboratory after bilateral lesioning of the suprachiasmatic nuclei, suggesting the involvement of clock genes in the aging process as they are in various disease conditions. Recent work has been shedding light on underlying pathways involved in the aging process, with the promise of interventions to extend healthy life spans. Caloric restriction, which is consistently and reproducibly associated with prolonging life in different animal models, is associated with an increased circadian amplitude. These results indicate the critical importance of chronobiology in dealing with problems of aging, from the circadian clock machinery orchestrating metabolism to the development of geroprotectors. The quantitative estimation of circadian rhythm characteristics interpreted in the light of time-specified reference values helps (1) to distinguish effects of natural healthy aging from those associated with disease and predisease; (2) to detect alterations in rhythm characteristics as markers of increased risk before there is overt disease; and (3) to individually optimize by timing prophylactic and/or therapeutic interventions aimed at restoring a disturbed circadian system and/or enhancing a healthy life span. Mapping changes in amplitude and/or acrophase that may overshadow any change in average value also avoids drawing spurious conclusions resulting from data collected at a fixed clock hour. Timely risk detection combined with treatment optimization by timing (chronotherapy) is the goal of several ongoing comprehensive community-based studies focusing on the well-being of the elderly, so that longevity is not achieved at the cost of a reduced quality of life.

Deregulation of CRTCs in Aging and Age-Related Disease Risk

“…Circadian rhythm is a tightly regulated internal biological clock, which modulates various physiological processes and undergoes changes with age [111][112][113][114]. In particular, dysregulation of circadian rhythm is associated with alterations in metabolism and development of cancers [115][116][117].…”

The Role of Food Antioxidants, Benefits of Functional Foods, and Influence of Feeding Habits on the Health of the Older Person: An Overview

“…We classify this sub-heading as being part of the process of senescence (natural ageing) or senility (pre-disease or during disease) [ 2 ], though temporal changes between the two states is often difficult to establish because of the experiment design which often focuses on the duration of study and required outcomes and confounding factors such as the inclusion/exclusion characteristics of the recruits to clinical trials (e.g., Body Mass Index (BMI), health definitions, birth cohort, etc.).…”

Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1

“…found that 43% of all protein-coding genes showed circadian oscillations in transcription somewhere in the body, largely in an organ-specific manner 8 . Additionally, the functionality of the circadian clock is attenuated or disrupted with age 9 , 10 . As a consequence, the disruption of the circadian clock has been associated with a variety of physio-pathological states, ranging from metabolic disorder to cancer.…”