Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2024

Eight-weeks of endurance exercise training prevents the progression of sarcopenic-obesity in aged mice (#10)

James Sligar 1 2 3 , Ashleigh Philp 1 2 3 4 , Dean Campelj 1 3 4 , Ross Laybutt 1 5 , Dorit Samocha-Bonet 1 3 , Andrew Philp 2 4 6
  1. Garvan Institute of Medical Research, Woollahra, NSW, Australia
  2. The University of Sydney, Sydney, NSW, Australia
  3. St Vincent's Clinical School UNSW Medicine, Sydney, NSW, Australia
  4. Centenary Institute, Sydney, NSW, Australia
  5. Westmead Institute of Medical Research, Sydney, NSW, Australia
  6. The University of Technology Sydney, Sydney, NSW, Australia

Background: Ageing causes reductions in skeletal muscle mass and strength, while increasing adiposity, a condition known as sarcopenic-obesity. We investigated whether endurance exercise training can ameliorate sarcopenic-obesity in aged mice. Methods: Male and female Mito-QC mice, expressing a tandem GFP:mCherry mitophagy reporter, were aged to 26-months. Gastrocnemius muscle was collected at 3, 12 and 24-months (n=9). Additionally, an 8-week progressive endurance treadmill exercise study was conducted in 24M mice (26M-EX), with non-exercise controls (26M-SED; n=9). Body composition was measured using echo-MRI, and mitochondrial respiration via high-resolution respirometry of permeabilised muscle fibre bundles. Mitophagy was quantified using immunofluorescence confocal microscopy. Results: Male lean/body mass decreased at 26M compared to 3M (p=0.0063), which was unchanged with exercise (p=0.0012). Female lean/body mass peaked at 3M and was unaffected by exercise. Male fat/body mass increased from 3M-12M (p=0.0018), then plateaued (p>0.05). Female fat/body mass was greater at 12M (p=0.0145) and 26M (p=0.0019) and decreased with exercise (p>0.05). Mitochondrial respiration did not change significantly from 3M to 24M in either sex (p>0.05). Male 26M-SED had a significant decrease in respiration (p=0.0103), whereas 26M-EX were not significantly different from 3M (p>0.05). While there was no significant difference in respiration in female 26M-SED (p>0.05), respiration was elevated in 26M-EX compared to 3M (p=0.0345). Mitophagy did not significantly change from 3 to 24M in either sex (p>0.05). The 26M-SED group displayed a hyper-mitophagic response compared to 3M (4-fold and 2-fold for males (p<0.0001) and females (p=0.0065), respectively). Mitophagy in 26M-EX was not significantly different from 3M in both sexes (p>0.05). Conclusion: Ageing caused a sarcopenic-obesity phenotype which was ameliorated by progressive endurance training. In parallel, exercise improved mitochondrial respiration and reduced mitophagy. Collectively, our results suggest that endurance training is an effective countermeasure to sarcopenic-obesity and that exercise-mediated improvements in mitochondrial turnover may underlie this protective effect.