Swimming exercise stimulates IGF1/ PI3K/Akt and AMPK/SIRT1/PGC1α survival signaling to suppress apoptosis and inflammation in aging hippocampus

Aging (Albany NY). 2020 Apr 22;12(8):6852-6864. doi: 10.18632/aging.103046. Epub 2020 Apr 22.

Abstract

Hippocampus is one of the most vulnerable brain regions in terms of age-related pathological change. Exercise is presumed to delay the aging process and promote health because it seems to improve the function of most of the aging mechanisms. The purpose of this study is to evaluate the effects of swimming exercise training on brain inflammation, apoptotic and survival pathways in the hippocampus of D-galactose-induced aging in SD rats. The rats were allocated to the following groups: (1) control; (2) swimming exercise; (3) induced-aging by injecting D-galactose; (4) induced-aging rats with swimming exercise. The longevity-related AMPK/SIRT1/PGC-1α signaling pathway and brain IGF1/PI3K/Akt survival pathway were significantly reduced in D-galactose-induced aging group compared to non-aging control group and increased after exercise training. The inflammation pathway markers were over-expressed in induced-aging hippocampus, exercise significantly inhibited the inflammatory signaling activity. Fas-dependent and mitochondrial-dependent apoptotic pathways were significantly increased in the induced-aging group relative to the control group whereas they were decreased in the aging-exercise group. This study demonstrated that swimming exercise not only reduced aging-induced brain apoptosis and inflammatory signaling activity, but also enhanced the survival pathways in the hippocampus, which provides one of the new beneficial effects for exercise training in aging brain.

Keywords: apoptosis; hippocampus; induced-aging rats; inflammatory; swimming exercise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / genetics
  • Adenylate Kinase / metabolism
  • Aging / pathology
  • Aging / physiology*
  • Animals
  • Apoptosis
  • Caspases / metabolism
  • Cyclooxygenase 2 / metabolism
  • Fas Ligand Protein / metabolism
  • Fas-Associated Death Domain Protein / metabolism
  • Gene Expression
  • Hippocampus / pathology
  • Hippocampus / physiology*
  • Inflammation / metabolism
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • NF-kappa B / metabolism
  • Neurons / pathology
  • Nitric Oxide Synthase Type II / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Receptor, IGF Type 1 / metabolism
  • Signal Transduction*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Swimming / physiology*
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-X Protein / metabolism

Substances

  • Bcl2l1 protein, rat
  • Fadd protein, rat
  • Fas Ligand Protein
  • Fas-Associated Death Domain Protein
  • Igf1r protein, rat
  • NF-kappa B
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Tumor Necrosis Factor-alpha
  • bcl-X Protein
  • insulin-like growth factor-1, rat
  • Insulin-Like Growth Factor I
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Cyclooxygenase 2
  • Phosphatidylinositol 3-Kinase
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt
  • Adenylate Kinase
  • Caspases
  • Sirt1 protein, rat
  • Sirtuin 1