The Biological Clock in Gray Mouse Lemur: Adaptive, Evolutionary and Aging Considerations in an Emerging Non-human Primate Model

Abstract

Circadian rhythms, which measure time on a scale of 24 h, are genetically generated by the circadian clock, which plays a crucial role in the regulation of almost every physiological and metabolic process in most organisms. This review gathers all the available information about the circadian clock in a small Malagasy primate, the gray mouse lemur ( Microcebus murinus ), and reports 30 years data from the historical colony at Brunoy (France). Although the mouse lemur has long been seen as a “primitive” species, its clock displays high phenotypic plasticity, allowing perfect adaptation of its biological rhythms to environmental challenges (seasonality, food availability). The alterations of the circadian timing system in M. murinus during aging show many similarities with those in human aging. Comparisons are drawn with other mammalian species (more specifically, with rodents, other non-human primates and humans) to demonstrate that the gray mouse lemur is a good complementary and alternative model for studying the circadian clock and, more broadly, brain aging and pathologies.

Survival is reduced when endogenous period deviates from 24 h in a non-human primate, supporting the circadian resonance theory

“…To address this issue, we focused on an emerging model in neurosciences, the gray mouse lemur (Microcebus murinus). This small nocturnal primate originates from Madagascar and displays aged-related impairments similar to those found in humans [15][16][17] , including circadian rhythms alterations, such as locomotor activity fragmentation or sleep deterioration [18][19][20] . In captivity, the gray mouse lemur can live to age 12 17 and its half-life is approximately 5-6 years 21,22 , whereas the lifespan is significantly lower in the wild 23 .…”

Physiological and cognitive consequences of a daily 26h photoperiod in a primate(M. murinus)

“…This small Malagasy lemur is an emerging model in neurosciences since it displays aged-related impairments similar to those found in humans (e.g. spontaneous neurodegenerative diseases or cognitive deficiencies, Bons et al, 2006; Joly et al, 2014; Languille et al, 2012; Picq et al, 2015), including circadian rhythms alteration, such as locomotor activity fragmentation or sleep deterioration (see Hozer et al, 2019 for review). On the other hand, its small body size and light body mass make it an ideal and promising laboratory model.…”

Adult survival is reduced when endogenous period deviates from 24h in a non-human primate (Microcebus murinus), depending on sex and season

“…In several mammalians, even within the same species, increasing, decreasing or constant endogenous periods with age have been found (Davis and Viswanathan, 1992; Kendall et al, 2001; Monk and Moline, 1989; Pittendrigh and Daan, 1976a; Possidente et al, 1995). In the gray mouse lemur, the same conflicting observations lead to suggest that tau evolution during aging is due to epigenetic variations between individuals and underline once again that aging is an individual-dependent phenomenon (Aujard et al, 2006; Hozer et al, 2019; Schilling et al, 2001). A longitudinal approach is necessary to bring further exhaustive information on the relationship between tau and aging.…”

“…To address this issue, we focused on an emerging model in neurosciences, the gray mouse lemur ( Microcebus murinus ). This small nocturnal primate originates from Madagascar and displays aged-related impairments similar to those found in humans (Bons et al, 2006; Joly et al, 2014; Languille et al, 2012; Picq et al, 2015), including circadian rhythms alteration, such as locomotor activity fragmentation or sleep deterioration (Aujard et al, 2006; Hozer et al, 2019; Pifferi et al, 2012, 2011). In captivity, the gray mouse lemur can live to age 12 (Languille et al, 2012) and its half-life is approximately 5-6 years (Perret, 1997; Pifferi et al, 2018), whereas the lifespan is significantly lower in the wild (Lutermann et al, 2006).…”