Aging circadian rhythms and cannabinoids

Abstract

Numerous aspects of mammalian physiology exhibit cyclic daily patterns, known as circadian rhythms. However, studies in aged humans and animals indicate that these physiological rhythms are not consistent throughout the life span. The simultaneous development of disrupted circadian rhythms and age-related impairments suggests a shared mechanism which may be amenable to therapeutic intervention. Recently, the endocannabinoid system has emerged as a complex signaling network which regulates numerous aspects of circadian physiology relevant to the neurobiology of aging. Agonists of cannabinoid receptor-1 (CB1) have consistently been shown to decrease neuronal activity, core body temperature, locomotion, and cognitive function. Paradoxically, several lines of evidence now suggest that very low doses of cannabinoids are beneficial in advanced age. One potential explanation for this phenomenon is that these drugs exhibit hormesis-a biphasic dose-response wherein low doses produce the opposite effects of higher doses. Therefore, it is important to determine the dose-, age-, and time-dependent effects of these substances on the regulation of circadian rhythms and other processes dysregulated in aging. This review highlights three fields-biological aging, circadian rhythms, and endocannabinoid signaling-to critically assess the therapeutic potential of endocannabinoid modulation in aged individuals. If the hormetic properties of exogenous cannabinoids are confirmed, we conclude that precise administration of these compounds may bidirectionally entrain central and peripheral circadian clocks and benefit multiple aspects of aging physiology.

Aging selectively dampens oscillation of lipid abundance in white and brown adipose tissue

“…The relation between the circadian system and aging has long been acknowledged, however the direction of this relationship remains elusive 7 . What is generally accepted, is that aging affects the entrainment of the central clock in various ways, and that dyssynchrony in the central clock can cause dysregulations in the peripheral clocks 32 . What is still under debate, however, is if peripheral clocks are individually affected upon aging, given that many age-induced effects appear to be tissue-specific 30 .…”

Cannabinoids, Endocannabinoids and Sleep

“…It has also been suggested that cannabis may act centrally as a zeitgeber (Whitehurst et al, 2015 ), entraining biological rhythms to facilitate daily sleep periods, and thus may serve as a chronobiotic therapeutic compound for individuals with disrupted circadian function, such as the elderly (Hodges and Ashpole, 2019 ). Evidence suggests there is also chronobiological activity in the eCB system itself in humans.…”

Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio)

“…For example, perinatal exposure to chemicals like dieldrin increased the risk of Parkinson's disease (Richardson et al 2006), while lead is linked to amyloid precursor protein dysfunction and Alzheimer's disease (Reviewed in: Zawia and Basha 2005). In contrast, preconditioning biological systems during critical developmental periods may bolster resilience to age-related dysfunction (Calabrese and Mattson 2017;Gidday 2015;Hodges and Ashpole 2019). Dietary restriction due to litter crowding in early life leads to increased life span (Sun et al 2009).…”