Promoting Healthspan & Healthy Aging Through Exercise
Healthspan is the period of our life without major debilitating diseases. In the modern world where unhealthy lifestyle choices and chronic diseases taper the healthspan, which lead to an enormous burden on your loved ones and friends, not to mention the financial burden that comes with none independent living.. It is therefore vital we preserves the quality of life and extend your healthspan for you and your family. Finding ways to promote healthspan becomes a pressing goal of the scientific community. Exercise, one of humanity’s most ancient and effective lifestyle interventions, appears to be at the centre of the solution since it can both treat and prevent the occurrence of many chronic diseases. In this series of blogs, I will review the current evidence and opinions about regular exercise promoting healthspan through enhancing the functionality of our organ systems and preventing diseases.
Two thousand and two hundred years have passed since the first Chinese emperor, Qin Shi Huang, ordered a nationwide hunt for the elixir for eternal life [1]. Throughout the history of modern medicine, much like the emperor’s dream, scientists have never halted the search for ways to extend our lifespan. In the past 50 years, extensive research and development with tremendous amount of investment have led to an increase of lifespan in the U.S. by 10 years [2]. In 2019, there were over 703 million of the world population aged 65 or more; this number is projected to be over 1.5 billion by 2050 [3]. However, healthspan, the period of our life without major debilitating diseases, has not been prolonged [2]. Because aging remains the most important risk factor for nearly all chronic diseases [4,5], this creates a conundrum that the extended lifespan without improvement of healthspan leads to significant aging of the society and unsustainable economy.
Lifespan in the U.S. has increased by 10 years, However, healthspan has not increased
Evidence and theories from research in the recent decades have shown that human life expectancy may have reached or come close to a limit set primarily by natural causes (chronic diseases) and genetics [6,7]. The concept of “healthy aging”, that is, to maximally expand the expectancy of healthy living before a person suffers from permanent aging-associated disabilities and chronic diseases, has emerged in the past two decades and gained significant popularity [8,9,10]. In the 21st century, there is a dire need of research on extending our healthspan [11,12,13]. Much like lifespan, healthspan can be influenced by numerous factors, namely genetics, environmental factors, social-economic status, lifestyle choices including dietary intake, physical activities, etc
Exercise as Medicine to Promote Healthspan
The most ancient and potent “medicine” known to mankind that promotes healthspan is the engagement in organised, repeated and purposeful physical activities, or exercise training. The first documented exercise prescriptions by surgeons can be traced back to thousands of years ago in various ancient civilisations like the Ancient Greece and the Yellow River Civilisation in China [14]. Over the recent decades, public health studies have shown indisputable evidence that high physical fitness is the most crucial factor for delaying all-cause mortality and the onset of chronic diseases, especially cardiovascular diseases, metabolic disorders and cancer [15,16,17]. Immense amount of research evidence has also demonstrated that long-term exercise training reshapes the molecular basis of multiple organ systems, including cardiorespiratory, musculoskeletal, neurological, endocrine and immune system [18,19,20]. For example, in a 12-year study in over 400,000 individuals, Wen et al. found the evidence that led to the conclusion that even 15 min a day or 90 min a week of moderate intensity exercise can reduce all-cause mortality [21].
15 min a day or 90 min a week of moderate intensity exercise can reduce all-cause mortality
Overall, exercise can be divided into two types: endurance and resistance exercise. Endurance exercise, often called aerobic exercise, is defined as exercise regimens that heavily rely on oxygen-utilizing energy metabolism, i.e., mitochondrial respiration, such as distance running, swimming and cycling. The main effects of endurance exercise include increase in mitochondrial content, capillary density, mass of slow-twitch oxidative myofibers and proportion of fast-twitch, oxidative myofibers in skeletal muscles along with enhanced cardiorespiratory function [22,23,24]. Resistance exercise, sometimes referred to as anaerobic exercise, relies primarily on anaerobic energy metabolism, namely creatine phosphate (CP) and anaerobic glycolysis for force production in a short period of time with less reliance on oxygen consumption. Typical resistance exercise regimens are heavy, low-rep weight training like deadlifts, squat, presses, pulls and sprinting. Adaptation of resistance exercise mainly include hypertrophy of the fast-twitch, glycolytic muscles, and usually does not or only moderately increase mitochondrial content [25,26]. Recent evidence suggests that although quantity of mitochondria might be unaltered, resistance exercise may still improve functionality of existing mitochondria, suggesting resistance exercise may also contribute to the regulation of mitochondrial quality [27].
Although the most direct executers of exercise are skeletal muscle and heart, regular exercise also leads to systemic changes in virtually all organ systems with superb, multifaceted benefits to health.
exercise training remains the most potent “medicine” that preserves quality of life and expands healthspan. The molecular understanding of exercise impacts in different organ systems reinstates that exercise is the most powerful lifestyle intervention against chronic diseases. While human lifespan seems to approach its limit, great potentials lie in promoting physical activities among any given communities to improve the healthspan and possibly lifespan as well.
In this series of in-depth Blogs, I will summarise current opinions and evidence on how exercise training is important in promoting healthspan through enhancing the functionality of the cardiovascular system, skeletal muscle, nervous system and preventing the occurrence of cancer.
In the next Blog I will discuss the cardiovascular system and the exercise benefits in promoting cardiovascular function.
References
1. Katz B. 2000-Year-Old Texts Reveal the First Emperor of China’s Quest for Eternal Life. [(accessed on 24 December 2021)]. Available online: https://www.smithsonianmag.com/smart-news/2000-year-old-texts-reveal-first-emperor-chinas-quest-eternal-life-180967671/
2. Medina L., Sabo S., Vespa J. Living Longer: Historical and Projected Life Expectancy in the United States, 1960 to 2060. U.S. Department of Commerce, U.S. Census Bureau; Suitland, MD, USA: 2020. [Google Scholar]
3. United Nations Department of Economic and Social Affairs Population Division . World Population Ageing 2020 Highlights: Living Arrangements of Older Persons (ST/ESA/SER.A/451) United Nations Department of Economic and Social Affairs; New York, NY, USA: 2020. [Google Scholar]
4. Zhang Z.D., Milman S., Lin J.R., Wierbowski S., Yu H., Barzilai N., Gorbunova V., Ladiges W.C., Niedernhofer L.J., Suh Y., et al. Genetics of extreme human longevity to guide drug discovery for healthy ageing. Nat. Metab. 2020;2:663–672. doi: 10.1038/s42255-020-0247-0. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
5. Pifferi F., Aujard F. Caloric restriction, longevity and aging: Recent contributions from human and non-human primate studies. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2019;95:109702. doi: 10.1016/j.pnpbp.2019.109702. [PubMed] [CrossRef] [Google Scholar]
6. Dong X., Milholland B., Vijg J. Evidence for a limit to human lifespan. Nature. 2016;538:257–259. doi: 10.1038/nature19793. [PubMed] [CrossRef] [Google Scholar]
7. Olshansky S.J., Carnes B.A., Cassel C. In search of Methuselah: Estimating the upper limits to human longevity. Science. 1990;250:634–640. doi: 10.1126/science.2237414. [PubMed] [CrossRef] [Google Scholar]
8. Pijnenburg M.A., Leget C. Who wants to live forever? Three arguments against extending the human lifespan. J. Med. Ethics. 2007;33:585–587. doi: 10.1136/jme.2006.017822. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
9. Goldman D.P., Cutler D., Rowe J.W., Michaud P.C., Sullivan J., Peneva D., Olshansky S.J. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Aff. 2013;32:1698–1705. doi: 10.1377/hlthaff.2013.0052. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
10. Nikolich-Žugich J., Goldman D.P., Cohen P.R., Cortese D., Fontana L., Kennedy B.K., Mohler M.J., Olshansky S.J., Perls T., Perry D., et al. Preparing for an Aging World: Engaging Biogerontologists, Geriatricians, and the Society. J. Gerontol. A Biol. Sci. Med. Sci. 2016;71:435–444. doi: 10.1093/gerona/glv164. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
11. Olshansky S.J. From Lifespan to Healthspan. JAMA. 2018;320:1323–1324. doi: 10.1001/jama.2018.12621. [PubMed] [CrossRef] [Google Scholar]
12. Olshansky S.J., Martin G.M., Kirkland J.L. Aging: The Longevity Dividend. Cold Spring Harbor Laboratory Press; Cold Spring Harbor, NY, USA: 2016. [Google Scholar]
13. Sierra F. The Emergence of Geroscience as an Interdisciplinary Approach to the Enhancement of Health Span and Life Span. Cold Spring Harb. Perspect. Med. 2016;6:a025163. doi: 10.1101/cshperspect.a025163. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
14. Tipton C.M. The history of “Exercise Is Medicine” in ancient civilizations. Adv. Physiol. Educ. 2014;38:109–117. doi: 10.1152/advan.00136.2013. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
15. Katzmarzyk P.T., Church T.S., Craig C.L., Bouchard C. Sitting time and mortality from all causes, cardiovascular disease, and cancer. Med. Sci. Sports Exerc. 2009;41:998–1005. doi: 10.1249/MSS.0b013e3181930355. [PubMed] [CrossRef] [Google Scholar]
16. Blair S.N., Kohl H.W., Paffenbarger R.S., Clark D.G., Cooper K.H., Gibbons L.W. Physical fitness and all-cause mortality. A prospective study of healthy men and women. JAMA. 1989;262:2395–2401. doi: 10.1001/jama.1989.03430170057028. [PubMed] [CrossRef] [Google Scholar]
17. Myers J., Prakash M., Froelicher V., Do D., Partington S., Atwood J.E. Exercise capacity and mortality among men referred for exercise testing. N. Engl. J. Med. 2002;346:793–801. doi: 10.1056/NEJMoa011858. [PubMed] [CrossRef] [Google Scholar]
18. Timmons J.A., Knudsen S., Rankinen T., Koch L.G., Sarzynski M., Jensen T., Keller P., Scheele C., Vollaard N.B., Nielsen S., et al. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J. Appl. Physiol. 2010;108:1487–1496. doi: 10.1152/japplphysiol.01295.2009. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
19. Ross R., de Lannoy L., Stotz P.J. Separate Effects of Intensity and Amount of Exercise on Interindividual Cardiorespiratory Fitness Response. Mayo Clin. Proc. 2015;90:1506–1514. doi: 10.1016/j.mayocp.2015.07.024. [PubMed] [CrossRef] [Google Scholar]
20. Keller P., Vollaard N.B., Gustafsson T., Gallagher I.J., Sundberg C.J., Rankinen T., Britton S.L., Bouchard C., Koch L.G., Timmons J.A. A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype. J. Appl. Physiol. 2011;110:46–59. doi: 10.1152/japplphysiol.00634.2010. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
21. Wen C.P., Wai J.P., Tsai M.K., Yang Y.C., Cheng T.Y., Lee M.C., Chan H.T., Tsao C.K., Tsai S.P., Wu X. Minimum amount of physical activity for reduced mortality and extended life expectancy: A prospective cohort study. Lancet. 2011;378:1244–1253. doi: 10.1016/S0140-6736(11)60749-6. [PubMed] [CrossRef] [Google Scholar]
22. Fletcher G.F., Balady G., Blair S.N., Blumenthal J., Caspersen C., Chaitman B., Epstein S., Sivarajan Froelicher E.S., Froelicher V.F., Pina I.L., et al. Statement on exercise: Benefits and recommendations for physical activity programs for all Americans. A statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association. Circulation. 1996;94:857–862. doi: 10.1161/01.cir.94.4.857. [PubMed] [CrossRef] [Google Scholar]
23. Harber M.P., Konopka A.R., Undem M.K., Hinkley J.M., Minchev K., Kaminsky L.A., Trappe T.A., Trappe S. Aerobic exercise training induces skeletal muscle hypertrophy and age-dependent adaptations in myofiber function in young and older men. J. Appl. Physiol. 2012;113:1495–1504. doi: 10.1152/japplphysiol.00786.2012. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
24. Akimoto T., Ribar T.J., Williams R.S., Yan Z. Skeletal muscle adaptation in response to voluntary running in Ca2+/calmodulin-dependent protein kinase IV-deficient mice. Am. J. Physiol. Cell Physiol. 2004;287:C1311–C1319. doi: 10.1152/ajpcell.00248.2004. [PubMed] [CrossRef] [Google Scholar]
25. Seynnes O.R., de Boer M., Narici M.V. Early skeletal muscle hypertrophy and architectural changes in response to high-intensity resistance training. J. Appl. Physiol. 2007;102:368–373. doi: 10.1152/japplphysiol.00789.2006. [PubMed] [CrossRef] [Google Scholar]
26. Schoenfeld B.J. Science and Development of Muscle Hypertrophy. Human Kinetics; Champaign, IL, USA: 2016. [Google Scholar]
27. Porter C., Reidy P.T., Bhattarai N., Sidossis L.S., Rasmussen B.B. Resistance Exercise Training Alters Mitochondrial Function in Human Skeletal Muscle. Med. Sci. Sports Exerc. 2015;47:1922–1931. doi: 10.1249/MSS.0000000000000605. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
