Aging and the clock: Perspective from flies to humans

Abstract

Endogenous circadian oscillators regulate molecular, cellular and physiological rhythms, synchronizing tissues and organ function to coordinate activity and metabolism with environmental cycles. The technological nature of modern society with round‐the‐clock work schedules and heavy reliance on personal electronics has precipitated a striking increase in the incidence of circadian and sleep disorders. Circadian dysfunction contributes to an increased risk for many diseases and appears to have adverse effects on aging and longevity in animal models. From invertebrate organisms to humans, the function and synchronization of the circadian system weakens with age aggravating the age‐related disorders and pathologies. In this review, we highlight the impacts of circadian dysfunction on aging and longevity and the reciprocal effects of aging on circadian function with examples from Drosophila to humans underscoring the highly conserved nature of these interactions. Additionally, we review the potential for using reinforcement of the circadian system to promote healthy aging and mitigate age‐related pathologies. Advancements in medicine and public health have significantly increased human life span in the past century. With the demographics of countries worldwide shifting to an older population, there is a critical need to understand the factors that shape healthy aging. Drosophila melanogaster, as a model for aging and circadian interactions, has the capacity to facilitate the rapid advancement of research in this area and provide mechanistic insights for targeted investigations in mammals.

Interacting influences of aging and Alzheimer's disease on circadian rhythms

“…Circadian rhythms undergo alterations during normal aging and exhibit more pronounced disturbances in AD. While this review has been limited to studies in mammals, age‐related circadian rhythm changes have also been investigated in Drosophila (for review, see De Nobrega & Lyons, ; Giebultowicz & Long, ). In mammals, both normal aging and AD are accompanied by alterations in the SCN, including decreased expression of neuropeptides and increased glial activation.…”

Longitudinal sleep efficiency in the elderly and its association with health

“…The other mechanism regulating sleep, the circadian rhythm, changes in older age. The mammalian circadian rhythm pacemaker, the hypothalamic suprachiasmatic nucleus, differs in older ages in terms of cellular composition, neural activity and neurotransmission, which may alter synchrony amongst neurons, response to light, and amplitude and period of the rhythm generated (De Nobrega & Lyons, ; Duffy, Zitting, & Chinoy, ). These may cause an earlier sleep time, increase the number of daytime naps and disrupt the continuity of night sleep.…”

“…The ageing world population is making age‐related health problems a major public health issue. Worsening sleep as we age has been recognised as a contributor towards health problems in the elderly (De Nobrega & Lyons, ). Predicted brain age using an electroencephalogram of sleep, has shown that people have healthier ageing if their estimated brain age is less than their chronological age (Sun et al., ).…”

Circadian rhythmicity and the community of clockworkers

“…Ageing is a normal part of developmental change, and thus, circadian clocks also change across the lifespan. Age‐related clock dysfunction and strategies to reinforce circadian cycles in order to diminish these perturbations are reviewed by De Nobrega and Lyons, (). The authors point out that the fruit fly is a classic model that can be used to study the interactions between the circadian clock and age‐related decline because of the short life span and the neurogenetic tools that are available (De Nobrega & Lyons, ).…”

“…Age‐related clock dysfunction and strategies to reinforce circadian cycles in order to diminish these perturbations are reviewed by De Nobrega and Lyons, (). The authors point out that the fruit fly is a classic model that can be used to study the interactions between the circadian clock and age‐related decline because of the short life span and the neurogenetic tools that are available (De Nobrega & Lyons, ). In mammals, ageing impacts SCN‐regulated pathways, including sleep timing and entrainment to the LD cycle (Michel & Meijer, ).…”