Muscle Psn gene combined with exercise contribute to healthy aging of skeletal muscle and lifespan by adaptively regulating Sirt1/PGC-1α and arm pathway

PLoS One. 2024 May 16;19(5):e0300787. doi: 10.1371/journal.pone.0300787. eCollection 2024.

Abstract

The Presenilin (Psn) gene is closely related to aging, but it is still unclear the role of Psn genes in skeletal muscle. Here, the Psn-UAS/Mhc-GAL4 system in Drosophila was used to regulate muscle Psn overexpression(MPO) and muscle Psn knockdown(MPK). Drosophila were subjected to endurance exercise from 4 weeks to 5 weeks old. The results showed that MPO and exercise significantly increased climbing speed, climbing endurance, lifespan, muscle SOD activity, Psn expression, Sirt1 expression, PGC-1α expression, and armadillo (arm) expression in aged Drosophila, and they significantly decreased muscle malondialdehyde levels. Interestingly, when the Psn gene is knockdown by 0.78 times, the PGC-1α expression and arm expression were also down-regulated, but the exercise capacity and lifespan were increased. Furthermore, exercise combined with MPO further improved the exercise capacity and lifespan. MPK combined with exercise further improves the exercise capacity and lifespan. Thus, current results confirmed that the muscle Psn gene was a vital gene that contributed to the healthy aging of skeletal muscle since whether it was overexpressed or knocked down, the aging progress of skeletal muscle structure and function was slowed down by regulating the activity homeostasis of Sirt1/PGC-1α pathway and Psn/arm pathway. Exercise enhanced the function of the Psn gene to delay skeletal muscle aging by up regulating the activity of the Sirt1/PGC-1α pathway and Psn/arm pathway.

MeSH terms

  • Aging / genetics
  • Aging / metabolism
  • Aging / physiology
  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Healthy Aging / genetics
  • Healthy Aging / metabolism
  • Healthy Aging / physiology
  • Longevity*
  • Muscle, Skeletal* / metabolism
  • Muscle, Skeletal* / physiology
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Physical Conditioning, Animal*
  • Signal Transduction*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Drosophila Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Sirtuin 1
  • Transcription Factors
  • Psn protein, Drosophila

Grants and funding

This work is supported by the Science and Technology Support Plan for Youth Innovation of Colleges and Universities of Shandong Province of China (No. 2023RW057), Natural Science Foundation of Shandong Province (No. ZR2020QC096), National Natural Science Foundation of China (NSFC) (No. 32000832). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.