Early-adulthood spike in protein translation drives aging via juvenile hormone/germline signaling

ABSTRACT: Protein translation (PT) declines with age in invertebrates, rodents, and humans. It has been assumed that elevated PT at young ages is beneficial to health and PT ends up dropping as a passive byproduct of aging. In Drosophila, we show that a transient elevation in PT during early-adulthood exerts long-lasting negative impacts on aging trajectories and proteostasis in later-life. Blocking the early-life PT elevation robustly improves life-/health-span and prevents age-related protein aggregation, whereas transiently inducing an early-life PT surge in long-lived fly strains abolishes their longevity/proteostasis benefits. The early-life PT elevation triggers proteostatic dysfunction, silences stress responses, and drives age related functional decline via juvenile hormone-lipid transfer protein axis and germline signaling. Our findings suggest that PT is adaptively suppressed after early-adulthood, alleviating later-life proteostatic burden, slowing down age-related functional decline, and improving lifespan. Our work provides a theoretical framework for understanding how lifetime PT dynamics shape future aging trajectories.

INSTRUMENT(S):

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Body Proper, Whole Body

DISEASE(S): Disease Free

SUBMITTER: james mobley  

LAB HEAD: James A Mobley

PROVIDER: PXD044118 | Pride | 2023-10-24

REPOSITORIES: Pride