Can exercise reverse ageing?
In March this year, the BBC reported that a drug had been trialled in animals that could reverse certain aspects of ageing causing old mice “to restore their stamina, coat of fur and even some organ function.” Inspired by this, I wanted to understand more about how the ageing process works and if exercise can have a similar effect on the body; can exercise reverse ageing?
What are senescent cells?
This trial drug, a peptide worked by reducing the number of senescent cells in the mice. As we age, irreparable DNA damage begins to accumulate in cells, one of three things will then happen to these cells. They will:
- Go through a healthy and normal type of self-destruction known as apoptosis
- Become senescent
- Turn cancerous
Cells that have become senescent lose the ability to divide but are still metabolically active causing damage to other cells that are proximal to them. This damage is due to the release of pro-inflammatory cytokines, growth factors and proteases, which together are known as a Senescence Associated Secretory Phenotype (SASP). SASP is a contributing factor to diseases of ageing including atherosclerosis and type 2 diabetes.
The peptide research drug that has such a positive impact on restoring the vitality and health of the mice is designed to specifically target the senescent cells, forcing them to commit cell-suicide, apoptosis.
The result of this is fur growth returns to furless patches within 2 weeks, the mice are able to run twice as far within 3 weeks, and liver and kidney function is dramatically improved by 4 weeks. Research has also shown that the lifespan of mice can be increased by 20% by the elimination of senescent cells.
This is all likely fantastic news for the future of disease prevention and staving off the ravages of ageing, but is there anything that we can practically do for ourselves now that can address the issue of senescent cells?
Diet, aerobic exercise and cell senescence
Let’s review some of the research that addresses the potential impact of exercise on senescence at the cellular level.
Research published in the March 2016 edition of Diabetes details the impact of feeding mice an approximation of a typical Western Fast Food Diet (FFD). One group of mice on the fast food diet were given access to a running wheel whilst another group was not. Regular exercise prevented the mice with access to the wheel from prematurely accumulating senescent cells and protected them from the whole-body metabolic dysfunction that is typically the result of a fast food diet.
Additionally, this study looked at a group of mice who were fed a FFD for 16 weeks with no access to a running wheel, then were given access to a running wheel for the following 14 weeks. After the 14 weeks of running wheel access these mice showed reduced senescent markers in visceral fat tissue (the fat that surrounds the internal organs). The researchers concluded that exercise may have a restorative action, reducing the negative impact of senescent cells.
If we can assume similar results will be seen in humans, this research appears to show that just being physically active, can mitigate cellular senescence and metabolic damage. Also importantly, the research suggests that there is value in taking up regular exercise if you have already become overweight from past eating patterns and lack of exercise… the message is it’s never too late!
Excessive calorie intake combined with a lack of physical activity appear to be major factors responsible for promoting chronic diseases associated with ageing and the evidence is pointing toward cellular senescence playing a critical role in this process.
In a study published in 2014, yet another group of mice were given access to a running wheel, they were also able to mitigate the negative effects of their fast food diet and lower the number of cells in fat deposits exhibiting markers of senescence and related inflammation. The authors sum up that research by suggesting that physical activity “may affect the abundance of senescent cells with advancing age, and exercise may partly mediate its salutary effects on multiple organ systems by preventing their accumulation and/or mediating their removal.” Another tick for exercise in combatting cellular senescence.
Although much research focused on the impact of exercise on cellular senescence looks at the impact of aerobic exercise and uses mice, we will now look at papers that focus on resistance exercise (strength training) and humans.
Strength training and cellular senescence
In 2017, researchers studied the levels of a senescence biomarker associated with physical function present in the fat tissue of the thighs of older women. Following 5 months of resistance training, the number of cells displaying this senescence biomarker was lower than before the intervention. It appears that resistance training can have a positive impact on senescent cells.
Other research highlights the fact that resistance training is known to positively impact the physical processes that cause ageing including cellular senescence, with the authors stating: “regular resistance training is a potent and effective countermeasure for skeletal muscle ageing.”
This is great news as even when older adults engage in resistance training there can be a lack of significant strength increases in response to their exercising. However when researchers look beyond just strength increases in older adults they find that something very beneficial is going on underneath the surface: metabolic and structural changes in response to resistance exercise that are important factors in increasing lean tissue and improving physical capabilities.
Resistance training is known to be beneficial in improving mitochondrial mass in older adults. It is hypothesised that damage to mitochondria is an important step in the progression of cell senescence and that resistance training can help to slow this process.
Can exercise make cellular senescence worse?
We have looked at the benefits of both aerobic and resistance exercise on cellular senescence, but can exercise ever accelerate or have a negative impact on cellular senescence? It appears that it can. In 2012, researchers studied club-level triathletes during and after 6 months of preparation for an Ironman Triathlon.
This research was likely undertaken because it is well known that endurance athletes preparing for gruelling events tend to be at greater risk of developing illness. This susceptibility is associated with senescent T cells. The researchers found that proportions of senescent T cells in blood did not change during preparation for the event, but by 2 weeks after the race proportions of senescent CD4+ T cells had increased 192% which could “compromise host protection to novel pathogens and increase athlete infection risk”.
The take home message here appears to be that partaking in relatively extreme endurance activity/events and undertaking the typical training regime suggested for these events may have a negative impact on the functioning of the immune system.
What can we do about cellular senescence?
As I’ve mentioned before, senescence is what happens to ageing cells that don’t delete themselves or turn cancerous, unable to divide but remaining metabolically active they take on a pro-inflammatory profile.
Imagine senescent cells as an untreated rotten tooth, threatening to spread damage to its neighbors. Senescent cell-killing drugs would be the dentist, who extracts the rotten tooth completely. Think of exercise as a renewed focus on dental hygiene; brushing, flossing and rinsing (or chest pressing, rowing and leg pressing) away the decay, and minimising its spread. This is how exercise has a positive impact on ageing.
Since currently, there are no available safe senescent-cell-neutralising drugs, it is wise to invest in being physically active on a daily basis. Walking will likely help and even more so engaging in regular strength training much like we suggested in our blog series how to be physically fit for life: part 1 and part 2.
1. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Marjolein P. Baar, Renata M.C. Brandt, Diana A. Putavet, Julian D.D. Klein, Kasper W.J. Derks, Benjamin R.M. Bourgeois, Sarah Stryeck, Yvonne Rijksen, Hester van Willigenburg, Danny A. Feijtel, Ingrid van der Pluijm, Jeroen Essers, Wiggert A. van Cappellen, Wilfred F. van IJcken, Adriaan B. Houtsmuller, Joris Pothof, Ron W.F. de Bruin, Tobias Madl, Jan H.J. Hoeijmakers, Judith Campisi, Peter L.J. de Keizer.
2. Exercise Prevents Diet-induced Cellular Senescence in Adipose Tissue. Marissa J. Schafer, Thomas A. White, Glenda Evans, Jason M. Tonne, Grace C. Verzosa, Michael B. Stout, Daniel L. Mazula, Allyson K. Palmer, Darren J. Baker, Michael D. Jensen, Michael S. Torbenson, Jordan D. Miller, Yasuhiro Ikeda, Tamara Tchkonia, Jan M. van Deursen, James L. Kirkland, Nathan K. LeBrasseur. Diabetes Mar 2016.
3. Ageing, cellular senescence and disease: the influence of diet and exercise. Thomas White, Glenda Evans, Grace Verzosa, Tamara Pirtskhalava, Tamara Tchkonia, Jordan Miller, James Kirkland and Nathan LeBrasseur
4. Post-Menopausal Effects of Resistance Training on Muscle Damage and Mitochondria. Thomas G. Manfredi, Ph.D, Michael Monteiro, MS, Linda S. Lamont, Ph.D., Maria Fiatarone Singh, M.D., Mona Foldvari, MS, Sebrina White, MS, Arthur Cosmas, Ph.D., and Maria L. Urso, Ph.D.
5. Cellular senescence biomarker p16INK4a+ cell burden in thigh adipose is associated with poor physical function in older women. Justice JN, Gregory H, Tchkonia T, LeBrasseur NK, Kirkland JL, Kritchevsky SB, Nicklas BJ.
6. The impact of 6-month training preparation for an Ironman triathlon on the proportions of naïve, memory and senescent T cells in resting blood. Cormac Cosgrove, Stuart D. R. Galloway, Craig Neal, et al. European Journal of Applied Physiology, 2012, Volume 112, Number 8, Page 2989.
7. Resistance training increases muscle mitochondrial biogenesis in patients with chronic kidney disease. Balakrishnan VS, Rao M, Menon V, Gordon PL, Pilichowska M, Castaneda F, Castaneda-Sceppa C. Clin J Am Soc Nephrol. 2010;5:996–1002.
8. Resistance training, sarcopenia, and the mitochondrial theory of aging. Johnston AP, De Lisio M, Parise G. Appl Physiol Nutr Metab. 2008;33:191–199.
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