Sleep, Aging, and Cellular Health: Aged-Related Changes in Sleep and Protein Homeostasis Converge in Neurodegenerative Diseases

Abstract

Many neurodegenerative diseases manifest in an overall aged population, the pathology of which is hallmarked by abnormal protein aggregation. It is known that across aging, sleep quality becomes less efficient and protein homeostatic regulatory mechanisms deteriorate. There is a known relationship between extended wakefulness and poorly consolidated sleep and an increase in cellular stress. In an aged population, when sleep is chronically poor, and proteostatic regulatory mechanisms are less efficient, the cell is inundated with misfolded proteins and suffers a collapse in homeostasis. In this review article, we explore the interplay between aging, sleep quality, and proteostasis and how these processes are implicated in the development and progression of neurodegenerative diseases like Alzheimer’s disease (AD). We also present data suggesting that reducing cellular stress and improving proteostasis and sleep quality could serve as potential therapeutic solutions for the prevention or delay in the progression of these diseases.

Aging‐related Alzheimer's disease‐like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus)

“…The vervet model may be useful to address several gaps in knowledge about factors that promote or protect from LOAD. For example, several lifestyle factors including sleep (Brzecka et al, 2018; Bubu et al, 2017; Hafycz & Naidoo, 2019; Mander et al, 2016; Mander, 2020; Phan & Malkani, 2019), social isolation (Evans et al, 2019; Friedler et al, 2015; National Academies of Sciences, Engineering & Medicine, 2020; Shankar et al, 2013), impaired peripheral glucose metabolism (An et al, 2018; Craft, 2012; Ferreira et al, 2018), and gut dysbiosis (Askarova et al, 2020; Kowalski & Mulak, 2019) have been suggested to increase the risk for developing AD. However, whether any of these factors are causal remains unclear.…”

“…The vervet model may be useful to address several gaps in knowledge about factors that promote or protect from LOAD. For example, several lifestyle factors including sleep (Brzecka et al, 2018;Bubu et al, 2017;Hafycz & Naidoo, 2019;Mander et al, 2016;Mander, 2020;Phan & Malkani, 2019), social isolation (Evans et al, 2019;Friedler et al, 2015; National Academies of Sciences,…”

CRYPTOCHROMES promote daily protein homeostasis

“…K, L Quantification of the amplitude of wheel-running activity and period length from the experiment shown in (I), (J), including pre-treatment, during treatment and post-drug treatment. Proteome imbalance is already very strongly, and in some cases causally, linked to a range of pathological conditions including chronic inflammation, various cancers, metabolic disorders and neurodegeneration (Yalcin & Hotamisligil, 2013;Agyemang et al, 2015;Labbadia & Morimoto, 2015;Harper & Bennett, 2016;Hadizadeh Esfahani et al, 2018;Hafycz & Naidoo, 2019;Costa-Mattioli & Walter, 2020;Yerbury et al, 2020). It is therefore quite plausible that proteome imbalance underlies the diverse range of phenotypes exhibited by CKO mice, including impaired body growth (Masuki et al, 2005;Bur et al, 2009), increased susceptibility to multiple cancers (Lee et al, 2010;Kettner et al, 2016;Mteyrek et al, 2017;, chronic inflammation (Narasimamurthy et al, 2012;Hand et al, 2016;Cao et al, 2017) and dysregulated insulin secretion/fat deposition on high fat diets (Barclay et al, 2013).…”

Role of Tau Protein in Remodeling of Circadian Neuronal Circuits and Sleep

“…The dysregulation of circadian clocks contributes to the decline in optimal functioning of the nervous system, ultimately leading to a reduction in the quality of life due to cognitive impairments and emotional stress (Touitou and Haus, 2000; Hastings et al, 2003; Hafycz and Naidoo, 2019). Therefore, since damaged circadian rhythms and sleep/wake cycles have been associated with an increase in disease susceptibility (Hastings et al, 2003; Gibson et al, 2009) it is important to determine the rather complex source of age-related circadian or sleep/wake dysfunction.…”