Dataset Information

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): LTQ Orbitrap Velos

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

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Publications

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

Kim Harper S HS Parker Danitra J DJ Hardiman Madison M MM Munkácsy Erin E Jiang Nisi N Rogers Aric N AN Bai Yidong Y Brent Colin C Mobley James A JA Austad Steven N SN Pickering Andrew M AM

Nature communications 20230818 1

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 aggregatio ...[more]

PMID: 37596266

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Project description:Muscle mass and strength reduce during ageing with a steeper decline in women around the age of 50, which suggests that the menopausal transition is one of the mechanisms for age-induced neuromuscular deteriorations. At the moment, there is no clear explanation for the decline in muscle properties although both physical exercise and maintaining near premenopausal estrogen levels by hormonal replacement have been helpful in their preservation. However, the molecular consequences of both treatments in skeletal muscle are mostly unknown. The goal of this genome-wide study was to investigate the transcriptional networks through which power training (PT) comprising of jumping activities and estrogen containing hormone replacement therapy (HRT) may aid in the prevention of functional limitation ensued from insufficient muscle mass and physical performance after menopause. We used m. vastus lateralis samples obtained from postmenopausal women participating in a yearlong randomized double-blinded placebo-controlled trial with PT and HRT interventions. Muscle samples were available from eight PT, ten HRT and nine control women. Women in the PT group participated in a progressive PT program comprising mostly of jumping exercises for lower limbs with additional resistance exercises for the upper body. HRT intervention was double-blinded. All participants used either estradiol/noretisterone acetate preparation or placebo. Using statistical threshold p-value <0.05 and |fold change| >1.2 we identified 665 genes being differentially expressed among the studied 50-57-yr-old postmenopausal women. We used the hierarchical clustering method with extensive enrichment analysis in order to reveal enrichment of known GO or KEGG functional categories among co-regulated gene-clusters. In the enrichment analysis false discovery rate was set to be less than 15%. Transcription of “response to contraction”-, “insulin signaling”- and “adipocytokine signaling”-genes were upregulated by PT. Both PT and HRT were similarly effective on transcriptional regulation of glycolytic energy metabolism and calcium signaling. The HRT specifically affected “mitochondrion”-genes. In addition, we identified functional categories, such as “muscle development”, which were changed during the trial in all study groups. Our study revealed transcriptional changes in several functional categories in thigh muscle tissue of early postmenopausal women. The results emphasize that during the first years of the postmenopausal period, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle mass and performance. More specifically, our findings indicate that PT and HRT may function through improving energy metabolism, improving the response to contraction, preserving functionality of mitochondria and reducing reorganization of muscle tissue. Therefore these treatments are recommended for preservation of adequate muscle mass and function. 54 samples, which formed 3 study groups with 2 timepoints, i.e., 8 power training subjects, 10 hormone replacement subjects and 9 controls. 6 control subjects had replicated samples resulting in a total of 60 hybridizations.

Dataset Information

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

Publications

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

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