bioRxiv Science⌕ Search

Biology subjects

Imai, S.-i.

Publications and source records attributed to Imai, S.-i..

2 recordsLinked to original sources

Aging reduces motivation through decreased Bdnf expression in the ventral tegmental area

Age-associated reduced motivation is a hallmark of neuropsychiatric disorders in the elderly. In our rapidly aging societies, it is critical to keep motivation levels high enough to promote healthspan and lifespan. However, how motivation is reduced during aging remains unknown. Here, we used multiple mouse models to evaluate motivation and related affective states in young and old mice. We also compared the effect of social isolation, a common stressor in aged populations, to those of aging. We found that both social isolation and aging decreased motivation in mice, but that Bdnf expression in the ventral tegmental area (VTA) was selectively decreased during aging. Furthermore, VTA-specific Bdnf knockdown in young mice recapitulated reduced motivation observed in old mice. These results demonstrate that maintaining Bdnf expression in the VTA could promote motivation to engage in effortful activities and potentially prevent age-associated neuropsychiatric disorders.

neuroscience↗

Age-associated sleep-wake patterns are altered with Prdm13 signaling in the dorsomedial hypothalamus and dietary restriction in mice

Old animals display significant alterations in sleep-wake patterns such as increases in sleep fragmentation and sleep propensity. Here we demonstrated that dorsomedial hypothalamus-specific PR-domain containing protein 13-knockout (DMH-Prdm13-KO) mice recapitulated age-associated sleep alterations such as sleep fragmentation and increased sleep attempts during sleep deprivation (SD). These phenotypes were further exacerbated during aging, with increased adiposity and decreased physical activity, resulting in shortened lifespan. Dietary restriction (DR), a well-known anti-aging intervention in diverse organisms, ameliorated age-associated sleep alterations, whereas these effects of DR were abrogated in DMH-Prdm13-KO mice. Moreover, overexpression of Prdm13 in the DMH ameliorated sleep fragmentation and excessive sleepiness during SD in old mice. Therefore, maintaining Prdm13 signaling in the DMH might play an important role to control sleep-wake patterns during aging.

physiology↗