Initiating improvement in all aspects: Exercise, ATP and longevity
March 21, 2022 By Dr. Don Fitz-Ritson, DC
No matter your age or ability, exercise will improve your physical and cognitive capabilities. Exercise will also initiate key biochemical reactions in your muscles, increasing your energy and body functions. Exercise needs to be done regularly and it can be manipulated by its duration, intensity, and can be combined in numerous ways. Exercise works best when its duration and intensity are progressively increased.
The Physical Activity Guidelines outline that all ages from preschool, children and adolescents should do moderate-to-vigorous physical activity daily. Adults should do at least 150 minutes to 300 minutes a week of moderate-intensity, or 75 minutes to 150 minutes a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity. They should also do muscle-strengthening activities on two or more days a week. Older adults should do multi-component physical activity that includes balance training as well as aerobic and muscle-strengthening activities. Pregnant and postpartum women should do at least 150 minutes of moderate-intensity aerobic activity a week.1
Exercise and mitrochondria ATP
One of the key roles of exercise is to stimulate the mitrochondria to produce more ATP energy. The trained muscle adapts to this stressor – exercise, via the mitrochondria, and is able to resist fatiguing at a higher rate of exercise. As an example, endurance training should be performed a minimum of 3/week, duration >15 minutes and intensity of 60-90% of maximum oxygen uptake. To increase your endurance and ATP production, the training should gradually either expand the duration, or raise the level of intensity to 75-90% of maximum oxygen uptake.2 Recently is was shown that a single bout of endurance exercise caused an acute increase in mitrochondrial ATP.3Different exercises like HIIT and resistance training, either separately or in combination, can improve at the translational level and increase mitrochondrial ATP production and muscle hypertrophy in all ages.4
For the clinically challenged population, low-load blood flow restricted resistance exercise (BFRRE) can stimulate whole-muscle growth and improve muscle function.5 Aging is not a factor, as those who maintain a high amount of physical activity have better mitochondrial capacity, similar to highly active younger adults.6 Chronic resistance training for 10 weeks in an aging group, found increased mitochondrial protein in skeletal muscles.7In another aging group, 12 weeks of HIIT resulted in significant increase in mitrochondria content in the muscles.8The more mitrochondria in muscles, equals increased production of ATP. Interestingly, in a study where exercise variables such as intensity and volume (duration/frequency) were manipulated, this promoted specific and diverse mitochondrial adaptations.9
Exercise restores function of the mitrochondria, returning muscle mass, strength, endurance and improves muscle health and quality of life.10
Nutrition and mitrochondria ATP
The more high quality and quantity of mitrochondria ATP that is synthesized via diet or exercise, the more energy and health the physically active person will have. Due to daily stresses and especially when exercising, certain nutrients will assist and benefit the mitrochrondia ATP system. The diet should be well balanced to deal with the increased energy demands. With moderate- or high-intensity exercise, the muscle fibers undergo micro trauma, which causes inflammation and affects the production of the mitrochondria ATP system. Antioxidants such as vitamins C,11 D,12 E13 and melatonin,14 along with a protein supplement,15 will control the inflammation and assist with the mitrochondria ATP production. AMPT16 will assist with the ATP-producing catabolic pathways, while suppressing the ATP-consuming anabolic pathways, and is necessary for homeostasis, along with the NAD+ dependent lysine deacetylase SIRT1.17 To protect the mitrochrondia ATP production during exercise, from oxidative stress, key nutrients are required, such as vitamin D,18 CoQ10, L Carnitine and alpha-lipoic acid.19 With regular moderate –high exercise training, the above supplements should be taken regularly, along with a good multi vitamin and minerals which will provide magnesium,20 and with added mushrooms, are necessary for numerous pathways in the ATP system.21
Epigenetics and methylation
Epigenetics is the field that studies gene expression changes heritable by meiosis and mitosis, by changes in chromatin and DNA conformation. The three major studied epigenetic mechanisms are DNA methylation, Histone modification, and regulation of noncoding RNA-associated genes.22 Recent evidence suggests that epigenetic modifications of the mitochondrial genome, including the DNA, could contribute to the etiology of human diseases. Environmental factors, as well as nuclear DNA genetic variants, have been found to impair mitrochondria DNA methylation patterns.23 A central role of both endurance and resistance exercise has been identified to reorganize sarcomeric proteins and to improve the capacity of cells to build efficient organelles. 24 However, care is needed because the same resistance exercise stimulus can illicit different epigenetic responses in resisted trained vs. sedentary men, and provides a molecular mechanism underpinning the need for differential training stimuli.25
Regular exercise improves metabolism and the metabolic phenotype in a number of tissues, including skeletal muscle. The changes are partly mediated by transcriptional responses that occur following each individual bout of exercise, which increases oxidative capacity and influences the function of myokines and extracellular vesicles that signal to other tissues. The epigenetic and transcriptional mechanisms that mediate the skeletal muscle gene expression response to exercise, as well as their upstream signaling pathways, leads to the following: Exercise is effective in the primary prevention of 35 chronic diseases. The adaptive response to exercise is an important contributor to these health benefits.26 Current research data suggest epigenetic modifications (DNA methylation and histone acetylation) and microRNAs (miRNAs) are responsive to acute aerobic and resistance exercise in brain, blood, skeletal and cardiac muscle, adipose tissue and even buccal cells. Six months of aerobic exercise alters whole-genome DNA methylation in skeletal muscle and adipose tissue and directly influences lipogenesis.27
Potential of exercise
In a systemic review, it was reported that resistance exercise in humans induced epigenetic changes with energy metabolism and insulin sensitivity, contributing to healthy skeletal muscle. Endurance exercise caused modifications to metabolism via changes in DNA methylation and specific miRNAs. However, both resistance and endurance exercises are necessary for a better physiological adaptation to properly tackle the increasing prevalence of non-communicable pathologies.28 The link connecting exercise and skeletal muscle adaptation, lies in the interplay between metabolism and epigenetics.
Researchers have stated that the key health benefit of physical activity is to extend the human healthspan, which is defined as the years of life spent in good health. Physical activity is physiologically stressful, causing damage to the body at the molecular, cellular, and tissue levels. The body’s response to this damage, however, is essentially to build back stronger. This process causes the release of exercise-related antioxidants and anti-inflammatories, and enhances blood flow. In the absence of physical activity, these responses are activated less. The cellular and DNA repair processes have been shown to lower the risk of diabetes, obesity, cancer, osteoporosis, Alzheimer’s and depression. The researchers state that the key take-home point is that because we evolved to be active throughout our lives, our bodies need physical activity to age well.29
Exercise also benefits telomeres which are located at the ends of mammalian chromosomes. It is one of the main indicators of biological age and is shortened with each cellular division. This shortening leads to changes in the expression of several genes that encode vital proteins with critical functions in many tissues throughout the body, and ultimately impacts cardiovascular, immune and muscle physiology. Exercise impacts DNA methylation and telomere length positively, but is shorter in over-trained athletes.30 Exercise may also regulate sperm telomere length with six weeks of intense exercise training.31
Parents can affect their offspring as shown by a systemic summary reporting that exercise-induced epigenetic changes can be observed in offspring and may play a pivotal role among the multifactorial intergenerational-health impact of exercise,32 and on cognitive benefit, which may be associated with hippocampal epigenetic programming in offspring.33 Paternal exercise protects changes in fetus development and placenta inflammation. It also promotes modifications in the ncRNA profiles, gene and protein expression in the hippocampus, left ventricle, skeletal muscle, tendons, liver and pancreas in the offspring, and provides a warning on the harmful effects of a paternal unhealthy lifestyle.34
Reversing epigenic age
In a landmark study, researchers mapped the genome-wide positions and activities of enhancers in skeletal muscle biopsies collected from young sedentary men pre and post six weeks of endurance exercise. There was evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise training and the modulation of disease risk in humans.35 This would indicate that exercise is preventative via its constant reinforcement of several physiological systems, and optimal levels of physical exercise/activity are essential for optimal health and wellbeing.36
In a groundbreaking study which included 43 healthy adult males between the ages of 50 and 72, half of the participants followed an eight-week treatment program that included diet, sleep, exercise -30 mins/day, and relaxation guidance plus supplemental probiotics and phytonutrients. The remaining participants served as the control group and received no intervention.
The researchers conducted DNAm analysis on saliva samples from participants, and epigenetic age was calculated using the online Horvath DNAmAge clock. Results found that the diet and lifestyle treatment in eight weeks was associated with a 3.23 year decrease in DNAmAge compared with controls. 37
The exercise-induced epigenetic imprint can be transient or permanent and contributes to the muscle memory, which allows the skeletal muscle to adapt to the exercise stimuli previously encountered. Exercise is health.
- Piercy K, et al. The Physical Activity Guidelines for Americans. JAMA. 2018 Nov 20; 320(19): 2020-2028.
- Hawley J. Adaptations of skeletal muscle to prolonged, intense endurance training. Clin Exp Pharmacol Physiol2002: 29: 218–222.
- Perry C, et al. Molecular Basis of Exercise-Induced Skeletal Muscle Mitochondrial Biogenesis: Historical Advances, Current Knowledge, and Future Challenges. Cold Spring Harb Perspect Med. 2018 Sep 4;8(9):a029686.
- Robinson M, et al. Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans. Cell Metab. 2017 Mar 7;25(3):581-592.
- Vissing K, et al. Myocellular Adaptations to Low-Load Blood Flow Restricted Resistance Training. Exerc Sport Sci Rev. 2020 Oct;48(4):180-187.
- Distefano G, et al. Physical activity unveils the relationship between mitochondrial energetics, muscle quality, and physical function in older adults. J Cachexia Sarcopenia Muscle. 2018 Apr;9(2):279-294.
- Mesquita P, et al. Acute and chronic effects of resistance training on skeletal muscle markers of mitochondrial remodeling in older adults. Physiol Rep. 2020 Aug;8(15):e14526.
- Wyckelsma V, et al. Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high-intensity exercise training. J Physiol. 2017 Jun 1;595(11):3345-3359.
- Granata C, et al. Training-Induced Changes in Mitochondrial Content and Respiratory Function in Human Skeletal Muscle. Sports Med. 2018 Aug;48(8):1809-1828.
- Hood D, et al. Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging. Annu Rev Physiol. 2019 Feb 10;81:19-41.
- Righi N, et al. Effects of vitamin C on oxidative stress, inflammation, muscle soreness, and strength following acute exercise: meta-analyses of randomized clinical trials. Eur J Nutr. 2020 Oct;59(7):2827-2839.
- Latham C, et al. Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health. Front Physiol. 2021 Apr 14;12:660498.
- Chou C, et al. Short-Term High-Dose Vitamin C and E Supplementation Attenuates Muscle Damage and Inflammatory Responses to Repeated Taekwondo Competitions: A Randomized Placebo-Controlled Trial. Int J Med Sci 2018 Jul 30;15(11):1217-1226.
- Reiter R, et al. Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Cell Mol Life Sci. 2017 Nov; 74(21): 3863-3881.
- Strasser B, et al. Role of Dietary Protein and Muscular Fitness on Longevity and Aging. Aging Dis. 2018 Feb 1;9(1):119-132.
- Pirkmajer S, et al. The role of AMPK in regulation of Na +,K +-ATPase in skeletal muscle: does the gauge always plug the sink? J Muscle Res Cell Motil. 2021 Mar;42(1):77-97.
- Radak Z, et al. The systemic role of SIRT1 in exercise mediated adaptation. Redox Biol. 2020 Aug;35:101467.
- Wimalawansa S. Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology (Basel). 2019 May 11;8(2):30.
- Pagano G, et al. Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures. Int J Mol Sci. 2020 Sep 25;21(19):7060.
- Zhang Y, et al. Can Magnesium Enhance Exercise Performance? Nutrients. 2017 Aug 28;9(9):946.
- Martel J, et al. Hormetic Effects of Phytochemicals on Health and Longevity. Trends Endocrinol Metab. 2019 Jun;30(6):335-346.
- Soci U, et al. Exercise Training and Epigenetic Regulation: Multilevel Modification and Regulation of Gene Expression. Adv Exp Med Biol. 2017;1000:281-322.
- Stoccoro A, et al. Mitochondrial DNA Methylation and Human Diseases. Int J Mol Sci. 2021 Apr 27;22(9):4594.
- Solsona R, et al. Molecular Regulation of Skeletal Muscle Growth and Organelle Biosynthesis: Practical Recommendations for Exercise Training. Int J Mol Sci. 2021 Mar 8;22(5):2741.
- Bagley J, et al. Epigenetic Responses to Acute Resistance Exercise in Trained vs. Sedentary Men. J Strength Cond Res. 2020 Jun;34(6):1574-1580.
- McGee S, et al. Exercise adaptations: molecular mechanisms and potential targets for therapeutic benefit. Nature Reviews Endocrinology. 202016, pages495–505.
- Denham J, et al. Exercise: putting action into our epigenome. Sports Med. 2014 Feb;44(2):189-209.
- Barrón-Cabrera E, et al. Epigenetic Modifications as Outcomes of Exercise Interventions Related to Specific Metabolic Alterations: A Systematic Review. Lifestyle Genom. 2019;12(1-6):25-44.
- Lieberman D, et al. The active grandparent hypothesis: Physical activity and the evolution of extended human healthspans and lifespans. PNAS. 2021; 118 (50):
- Sellami M, et al. Regular, Intense Exercise Training as a Healthy Aging Lifestyle Strategy: Preventing DNA Damage, Telomere Shortening and Adverse DNA Methylation Changes Over a Lifetime. Front Genet. 2021 Aug 6;12:652497.
- Denham J. The association between sperm telomere length, cardiorespiratory fitness and exercise training in humans. Biomed J. 2019 Dec;42(6):430-433.
- Axsom J, et al. Impact of parental exercise on epigenetic modifications inherited by offspring: A systematic review. Physiol Rep. 2019 Nov;7(22):e14287.
- Goli P, et al. Intergenerational influence of paternal physical activity on the offspring’s brain: A systematic review and meta-analysis. Int J Dev Neurosci. 2021 Feb;81(1):10-25.
- Vieira de Sousa Neto I, et al. Impact of paternal exercise on physiological systems in the offspring. Acta Physiol (Oxf). 2021 Apr;231(4):e13620.
- Williams K, et al. Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human healJ Molecular Metab. Nov 2021, 53 (1-13).
- Hart D, et al. Optimal Human Functioning Requires Exercise Across the Lifespan: Mobility in a 1g Environment Is Intrinsic to the Integrity of Multiple Biological Systems. Front Physiol. 2020 Feb 27;11:156.
- Fitzgerald K, et al. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging (Albany NY).2021;13(7):9419-9432.
DR. DON FITZ-RITSON is a chiropractor and a rehab specialist. He was an Assistant Professor at CMCC. He published 17 papers and 3 chapters on chiropractic.He co-invented a laser and it received 7 Health Canada Approvals. He is focused on helping the aging population live better lives.
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