Overview of age‐related changes in psychomotor and cognitive functions in a prosimian primate, the gray mouse lemur (Microcebus murinus): Recent advances in risk factors and antiaging interventions

Abstract

Aging is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. Impaired glucose homeostasis is a major risk factor for cognitive decline in middle‐aged humans, pointing at the existence of early markers of unhealthy aging. The gray mouse lemur (Microcebus murinus), a small lemuriform Malagasy primate, shows relatively slow aging with decreased psychomotor capacities at middle‐age (around 5‐year old). In some cases (∼10%), it spontaneously leads to pathological aging. In this case, some age‐related deficits, such as severe cognitive decline, brain atrophy, amyloidosis, and glucoregulatory imbalance are congruent with what is observed in humans. In the present review, we inventory the changes occurring in psychomotor and cognitive functions during healthy and pathological aging in mouse lemur. It includes a summary of the cerebral, metabolic, and cellular alterations that occur during aging and their relation to cognitive decline. As nutrition is one of the major nonpharmacological antiaging strategies with major potential effects on cognitive performances, we also discuss its role in brain functions and cognitive decline in this species. We show that the overall approach of aging studies in the gray mouse lemur offers promising ways of investigation for understanding, prevention, and treatments of pathological aging in humans.

Cognitive performance of grey mouse lemurs (Microcebus murinus) during a discrimination learning task: Effect of the emotional valence of stimuli

“…The success rate tended to decrease with age (Figure S1). This age effect is consistent with classic ndings as well as most of the studies on the age effect on the cognitive abilities of mouse lemurs (Chaudron et al, 2021). This cognitive impairment effect was found in all six experimental conditions.…”

Cognitive performance is linked to fitness in a wild primate

“…In mouse lemurs, this CCS was influenced by age and exploration, but not by sex or body mass, with older and more explorative individual performing less good. Cognitive senescence has been documented in captive mouse lemurs, with individuals being older than 5 years exhibiting deficits in memory, flexible learning, and spatial abilities ( 54 ). However, unlike their captive conspecifics, wild mouse lemurs do not seem to exhibit functional senescence ( 48 ).…”

Increased oligodendrogenesis and myelination in the subventricular zone of aged mice and gray mouse lemurs

“…Considering its size and weight, the lemur has a relatively long life expectancy, four times longer than mammals with an equivalent body mass (reviewed in Languille et al., 2012 ), suggesting that lemurs could provide further knowledge on aging processes ( Ezran et al., 2017 ; Languille et al., 2012 ; Perret, 1997 ; Pifferi et al., 2014 ; Rahman et al., 2017 ). The lemur shows features identical to human cerebral aging (reviewed in Languille et al., 2012 ) and spontaneously develops age-related deficits, such as (1) biological rhythm disorders, including abnormal sleep/wake rhythms ( Cayetanot et al., 2005 ); (2) hormonal secretion disruption ( Aujard et al., 2001 ; Perret and Aujard, 2006 ; Pifferi et al., 2014 ); (3) cognitive decline, including reduced executive function and spatial memory ( Chaudron et al., 2021 ; Languille et al., 2012 , 2015 ; Picq et al., 2012 ); as well as (4) Alzheimer disease-related neuropathologies ( Laurijssens et al., 2013 ). Finally, neurogenesis has been recently described in the lemur SVZ and OB ( Royo et al., 2018 ).…”