Part 7. The lack of physical exercise can have deleterious effects on mitochondrial function. Physical inactivity has been associated with the following diseases:
- Cardiovascular disease
- Cancer
- Alzheimer’s disease
- Type 2 diabetes
- Parkinson’s disease
Low cardiorespiratory fitness is considered to be responsible for the highest percentage of all attributable fractions for all-cause mortality. No metric predicts risk for all-cause mortality better than VO2 max1.
This study by Houston et2 al found a 24% decrease in mitomitochondrial
function surrogate, succinate dehydrogenase (SDH), after 15 days of detraining in distance
runners.
Coyle et al3 observed that 56 days of detraining elicited a 40% decrease in
mitochondrial oxidative enzyme levels and a 22% increase in lactagenic enzyme lactate dehydrogenase (LDH) levels with increased blood lactate accumulation during exercise.
Fritzen et al4 found that 4 weeks of detraining in healthy male subjects elicited a decrease
of 32% in the activity of another mitochondrial function surrogate, citrate synthase (CS),
and a 29–36% decrease in mitochondrial complexes I–IV.
Houmard and colleagues5 showed a decrease in CS activity of 25% with just 14 days of detraining.
Alibegovic and colleagues6 elegantly showed that 9 days of bed rest altered more than 4500 genes and downregulated 34 metabolic pathways mainly associated with mitochondrial biogenesis, function, and OXPHOS [133]. In total, 54% of all genes involved in OXPHOS were downregulated. Moreover, bed rest elicited changes in the DNA methylation of the PPARGC1A gene, which encodes for PGC-1alpha. This is a master regulator of mitochondrial biogenesis. For this study, retraining for four weeks improved the altered genetic expression by 82%. This demonstrates the powerful effect that physical activity can have to restore major losses in favorable genetic expression.
Furthermore, bed rest induces changes in substrate partitioning. Glycolysis is favored over OXPHOS with a 37% deccrease in fat oxidation and a 21% increase in carbohydrate (CHO) metabolism.
To top it off. Bed rest does increase insulin resistance which occurs primarily in the skeletal muscle. This finding is quoted by 4 studies in San-Millan’s review paper.
Works cited
1. Kokkinos P, Faselis C, Samuel IBH, Pittaras A, Doumas M, Murphy R, Heimall MS, Sui X, Zhang J, Myers J. Cardiorespiratory Fitness and Mortality Risk Across the Spectra of Age, Race, and Sex. J Am Coll Cardiol. 2022 Aug 9;80(6):598-609. doi: 10.1016/j.jacc.2022.05.031. PMID: 35926933.
2. Houston, M.E.; Bentzen, H.; Larsen, H. Interrelationships between skeletal muscle adaptations and performance as studied by detraining and retraining. Acta Physiol. Scand. 1979, 105, 163–170.
3. Coyle, E.F.; Martin, W.H., 3rd; Bloomfield, S.A.; Lowry, O.H.; Holloszy, J.O. Effects of detraining on responses to submaximal exercise. J. Appl. Physiol. 1985, 59, 853–859.
4. Fritzen, A.M.; Thøgersen, F.B.; Thybo, K.; Vissing, C.R.; Krag, T.O.; Ruiz–Ruiz, C.; Risom, L.; Wibrand, F.; Høeg, L.D.; Kiens, B.; et al. Adaptations in Mitochondrial Enzymatic Activity Occurs Independent of Genomic Dosage in Response to Aerobic Exercise Training and Deconditioning in Human Skeletal Muscle. Cells 2019, 8, 237.
5. Houmard, J.A.; Hortobágyi, T.; Johns, R.A.; Bruno, N.J.; Nute, C.C.; Shinebarger, M.H.; Welborn, J.W. Effect of short–term training cessation on performance measures in distance runners. Int. J. Sport. Med. 1992, 13, 572–576.
6. Alibegovic, A.C.; Sonne, M.P.; Højbjerre, L.; Bork–Jensen, J.; Jacobsen, S.; Nilsson, E.; Færch, K.; Hiscock, N.; Mortensen, B.; Friedrichsen, M. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men. Am. J. Physiol.–Endocrinol. Metab. 2010, 299, E752–E763.
