Skip to main content
Log in

Exercise Against Aging: Darwinian Natural Selection Among Fit and Unfit Cells Inside Human Body

  • Original article
  • Published:
Journal of Science in Sport and Exercise Aims and scope Submit manuscript

Abstract

Exercise inevitably induces damages and triggers a brief inflammation in challenged tissues of the human body. Nevertheless, regular exercise is associated with improved physical fitness and lower all-cause mortality among adults in a dose-dependent manner. The paradox between destructive nature of exercise and its anti-aging benefit can be best explained by decreasing aged cell population of the human body in a Darwinian natural selection fashion, resulting in tissue renewal. In this concept, the unfit-to-fit cell ratio of a multicellular system increases during growth (expansion of cell population and size) and decreases after exercise challenges. Inflammation serves as an innate mechanism to recognize cells in danger and triggers clearance mechanism to eliminate unhealthy cells followed by regeneration. A recent finding of decreased p16INK4a+ senescent cells together with CD68+ macrophage infiltration in human skeletal muscle after resistance exercise supports this concept. The senescent cells are mostly stem cells located in capillaries surrounding myofibers, functioning to replace short-lived endothelial cells. They can be found in young men aged 20–25 years. In this context, exercise controls weight gain (i.e. cell number and size) and decrease senescent cell proportion in capillaries of the human body, providing benefits in physical fitness and increasing life expectancy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Thompson AL, Koehler E, Herring AH, Paynter L, Du S, Zhang B, Popkin B, Gordon-Larsen P. Weight gain trajectories associated with elevated C-reactive protein levels in Chinese adults. J Am Heart Assoc. 2016;5(9):e003262.

    Article  Google Scholar 

  2. Solon-Biet Samantha M, McMahon Aisling C, Ballard J, William O, Ruohonen K, Wu Lindsay E, Cogger Victoria C, Warren A, Huang X, Pichaud N, Melvin Richard G, Gokarn R, Khalil M, Turner N, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 2014;19(3):418–30.

    Article  CAS  Google Scholar 

  3. Mattison JA, Colman RJ, Beasley TM, Allison DB, Kemnitz JW, Roth GS, Ingram DK, Weindruch R, de Cabo R, Anderson RM. Caloric restriction improves health and survival of rhesus monkeys. Nat Commun. 2017;8:14063.

    Article  CAS  Google Scholar 

  4. Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng C-W, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK, Wei M, et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014;19(3):407–17.

    Article  CAS  Google Scholar 

  5. Sallis J. Age-related decline in physical activity: a synthesis of human and animal studies. Med Sci Sports Exerc. 2000;32(9):1598–600.

    Article  CAS  Google Scholar 

  6. Yang C, Jiao Y, Wei B, Yang Z, Wu J-F, Jensen J, Jean W-H, Huang C-Y, Kuo C-H. Aged cells in human skeletal muscle after resistance exercise. Aging US. 2018;10(6):1356.

    Article  Google Scholar 

  7. Erben RG, Odörfer KI, Siebenhütter M, Weber K, Rohleder S. Histological assessment of cellular half-life in tissues in vivo. Histochem Cell Biol. 2008;130(5):1041–6.

    Article  CAS  Google Scholar 

  8. Spalding KL, Bhardwaj RD, Buchholz BA, Druid H, Frisén J. Retrospective birth dating of cells in humans. Cell. 2005;122(1):133–43.

    Article  CAS  Google Scholar 

  9. Schafer MJ, White TA, Evans G, Tonne JM, Verzosa GC, Stout MB, Mazula DL, Palmer AK, Baker DJ, Jensen MD, Torbenson MS, Miller JD, Ikeda Y, et al. Exercise prevents diet-Induced cellular senescence in adipose tissue. Diabetes. 2016;65(6):1606–15.

    Article  CAS  Google Scholar 

  10. Samitz G, Egger M, Zwahlen M. Domains of physical activity and all-cause mortality: systematic review and dose–response meta-analysis of cohort studies. Int J Epidemiol. 2011;40(5):1382–400.

    Article  Google Scholar 

  11. Löllgen H, Böckenhoff A, Knapp G. Physical activity and all-cause mortality: an updated meta-analysis with different intensity categories. Int J Sports Med. 2009;30(03):213–24.

    Article  Google Scholar 

  12. Byberg L, Melhus H, Gedeborg R, Sundström J, Ahlbom A, Zethelius B, Berglund LG, Wolk A, Michaëlsson K. Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort. BMJ. 2009;338:b688.

    Article  Google Scholar 

  13. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL, van Deursen JM. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479:232.

    Article  CAS  Google Scholar 

  14. Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Ibrahim JG, Thomas NE, Sharpless NE. Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell. 2009;8(4):439–48.

    Article  CAS  Google Scholar 

  15. Wu J, Saovieng S, Cheng I-S, Liu T, Hong S, Lin C-Y, Su I-C, Huang C-Y and Kuo C-H. Ginsenoside Rg1 supplementation clears senescence-associated β-galactosidase in exercising human skeletal muscle. J Ginseng Res. 2018 (in press).

  16. Cauza E, Hanusch-Enserer U, Strasser B, Ludvik B, Metz-Schimmerl S, Pacini G, Wagner O, Georg P, Prager R, Kostner K, Dunky A, Haber P. The relative benefits of endurance and strength training on the metabolic factors and muscle function of people with type 2 diabetes mellitus. Arch Phys Med Rehabil. 2005;86(8):1527–33.

    Article  Google Scholar 

  17. Hosios AM, Hecht VC, Danai LV, Johnson MO, Rathmell JC, Steinhauser ML, Manalis SR, Vander Heiden MG. Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells. Dev Cell. 2016;36(5):540–9.

    Article  CAS  Google Scholar 

  18. Navone SE, Marfia G, Nava S, Invernici G, Cristini S, Balbi S, Sangiorgi S, Ciusani E, Bosutti A, Alessandri G. Human and mouse brain-derived endothelial cells require high levels of growth factors medium for their isolation, in vitro maintenance and survival. Vasc Cell. 2013;5(1):10.

    Article  CAS  Google Scholar 

  19. Friedl P, Tatje D, Czpla R. An optimized culture medium for human vascular endothelial cells from umbilical cord veins. Cytotechnology. 1989;2(3):171–9.

    Article  CAS  Google Scholar 

  20. Cribb PJ, Hayes A. Effects of supplement-timing and resistance exercise on skeletal muscle hypertrophy. Med Sci Sports Exerc. 2006;38(11):1918–25.

    Article  Google Scholar 

  21. Esmarck B, Andersen J, Olsen S, Richter EA, Mizuno M, Kjær M. Timing of postexercise protein intake is important for muscle hypertrophy with resistance training in elderly humans. J Physiol. 2001;535(1):301–11.

    Article  CAS  Google Scholar 

  22. Kay MM. Mechanism of removal of senescent cells by human macrophages in situ. Proc Natl Acad Sci USA. 1975;72(9):3521–5.

    Article  CAS  Google Scholar 

  23. Alley DE, Metter EJ, Griswold ME, Harris TB, Simonsick EM, Longo DL, Ferrucci L. Changes in weight at the end of life: characterizing weight loss by time to death in a cohort study of older men. Am J Epidemiol. 2010;172(5):558–65.

    Article  Google Scholar 

  24. Tsygankov D, Liu Y, Sanoff HK, Sharpless NE, Elston TC. A quantitative model for age-dependent expression of the p16INK4a tumor suppressor. PNAS. 2009;106(39):16562–7.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chia-Hua Kuo.

Ethics declarations

Conflict of interest

Part of the data reported in the paper is involved with a research funded by Nuliv Science, USA and Ministry of Science & Technology, Taiwan, China. US patent has been submitted in 2018.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kuo, CH. Exercise Against Aging: Darwinian Natural Selection Among Fit and Unfit Cells Inside Human Body. J. of SCI. IN SPORT AND EXERCISE 1, 54–58 (2019). https://doi.org/10.1007/s42978-019-0002-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42978-019-0002-y

Keywords

Navigation