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Reactivation of RNA metabolism underlies somatic restoration after adult reproductive diapause in C. elegans.

ABSTRACT: The mechanisms underlying biological aging are becoming recognized as therapeutic targets to delay the onset of multiple age-related morbidities. Even greater health benefits can potentially be achieved by halting or reversing age-associated changes. C. elegans restore their tissues and normal longevity upon exit from prolonged adult reproductive diapause, but the mechanisms underlying this phenomenon remain unknown. Here, we focused on the mechanisms controlling recovery from adult diapause. Here, we show that functional improvement of post-mitotic somatic tissues does not require germline signaling, germline stem cells, or replication of nuclear or mitochondrial DNA. Instead a large expansion of the somatic RNA pool is necessary for restoration of youthful function and longevity. Treating animals with the drug 5-fluoro-2'-deoxyuridine prevents this restoration by blocking reactivation of RNA metabolism. These observations define a critical early step during exit from adult reproductive diapause that is required for somatic rejuvenation of an adult metazoan animal.

SUBMITTER: Burnaevskiy N

PROVIDER: S-EPMC6089596 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Reactivation of RNA metabolism underlies somatic restoration after adult reproductive diapause in <i>C. elegans</i>.

Burnaevskiy Nikolay N Chen Shengying S Mailig Miguel M Reynolds Anthony A Karanth Shruti S Mendenhall Alexander A Van Gilst Marc M Kaeberlein Matt M

eLife 20180802

The mechanisms underlying biological aging are becoming recognized as therapeutic targets to delay the onset of multiple age-related morbidities. Even greater health benefits can potentially be achieved by halting or reversing age-associated changes. <i>C. elegans</i> restore their tissues and normal longevity upon exit from prolonged adult reproductive diapause, but the mechanisms underlying this phenomenon remain unknown. Here, we focused on the mechanisms controlling recovery from adult diapa ...[more]

PMID: 30070633

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Project description:For many insects, diapause is the primary mechanism for surviving unfavorable seasons. Some aspects of diapause regulation are well known, but we still lack a mechanistic understanding of molecular mechanisms that control the diapause pathway. Accumulating evidence suggests microRNAs regulate diapause in evolutionarily diverse insect species including flesh flies and moths, and, it is likely that microRNAs regulate multiple characteristics of diapause, including arrested egg follicle development and fat hypertrophy, in females of the Northern house mosquito, Culex pipiens. To investigate microRNA regulation of diapause in this species, we measured changes in egg follicle development and total lipid content over 22 days following adult emergence. We also evaluated changes in the abundance of candidate microRNAs associated with these physical changes during the same time frame. We found egg follicle size and lipid content were nearly the same in diapausing and nondiapausing females on the day of adult emergence, and then diverged over time such that by day 22 diapausing females had significantly smaller egg follicles and higher total lipids than their nondiapausing counterparts. Several microRNAs associated with lipid metabolism in insects, including miR-14-3p, miR-277-3p, and miR-305-5p, were underexpressed in diapausing females compared to nondiapausing females on the day of adult emergence, which suggests microRNA regulation occurs ahead of observed changes in these two features of the diapause phenotype. We also found miR-309-3p, miR-375-3p which stimulate ovarian development in other mosquito species, were underexpressed in diapausing females of Cx. pipiens at times after diapause is fully established and may be responsible for the arrest in ovarian development in this species. Taken together, our results demonstrate that changes in the abundance of some microRNAs is associated with phenotypic changes in diapause Cx. pipiens and suggests this epigenetic mechanism is part of the molecular toolkit regulating diapause.

Dataset Information

Reactivation of RNA metabolism underlies somatic restoration after adult reproductive diapause in C. elegans.

Publications

Reactivation of RNA metabolism underlies somatic restoration after adult reproductive diapause in <i>C. elegans</i>.

Similar Datasets

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