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Mitochondrial Therapy Improves Aspects of Aging in Older Mice

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A new mouse study has found that injecting healthy mitochondria from young mice into older mice improves learning and memory, skeletal muscle function, and immune system activity [1].

The Aging Mitochondria

Mitochondria are incredibly important components of our cells, as they produce energy in the form of ATP, the “molecular unit of currency” of intracellular energy transfer. They contain their own DNA, which is separate from the DNA in the cell nucleus. However, mitochondrial DNA is more prone to damage and mutations and lacks the full range of repair machinery that nuclear DNA has. This allows mutations, which greatly disrupt mitochondrial function, to accumulate [2].

Besides being the main source of energy in our cells, mitochondria are also the main source of dangerous free radicals called reactive oxygen species (ROS). Healthy mitochondria are able to neutralize these free radicals with antioxidants, but dysfunctional mitochondria have a harder time doing so.



As we get older, our mitochondria become overwhelmed by mutations, causing them to produce less and less energy. They also become much less effective at neutralizing ROS, which leak out and damage surrounding cells and tissues [3].

Mitochondrial dysfunction is one of the nine hallmarks of aging, and research suggests that it directly contributes to age-related diseases, including Alzheimer’s disease [4]. Therapies that target mitochondrial dysfunction may be an effective way to slow or possibly even reverse some aspects of aging.

Mitotherapy

Mitochondrial therapy (mitotherapy) is the transfer of healthy, functional mitochondria into cells that contain defective mitochondria in order to help restore tissue and organ function. It’s a relatively new therapy that shows promise for addressing a number of diseases that are characterized by mitochondrial dysfunction. This therapy’s potential comes from the fact that dysfunctional cells have mechanisms in place that allow them to take in healthy mitochondria from other cells, such as stem cells, and replace their damaged mitochondria [5].

The same researchers behind this recent study previously found that mitotherapy helped protect mice from liver damage caused by a high-fat diet and the pain-relieving drug acetaminophen (Tylenol) [3, 6]. The researchers speculated that given mitochondria’s crucial role in aging, mitotherapy might also help improve age-related physical and cognitive decline.



To test this hypothesis, they took healthy, mutation-free mitochondria from young mice and injected them into older mice. Then, they used powerful microscopes to peer into the cells in the older mice’s brains and skeletal muscle, two tissues that have especially large numbers of mitochondria and are sensitive to age-related declines in mitochondrial function. They found that the brain and muscle cells of the aged mice adopted the new, healthy mitochondria.

They also found that levels of key enzymes needed by mitochondria to make ATP were significantly increased in the older mice after the therapy. Conversely, levels of ROS and oxidative stress were significantly decreased in the cells, as the new mitochondria were able to effectively deal with any free radicals being produced.

Cognitive and Muscle Function

As we age, so do our brains. This manifests as trouble remembering things and issues with concentration, focus, and learning. To determine whether mitotherapy could improve cognitive function, the researchers observed how quickly the mice could swim around and find a submerged platform in a large circular pool (Morris water navigation task). Pre-therapy, older mice took much longer than younger mice to find the platform the second time around. However, after mitotherapy, the older mice found the platform much more quickly, suggesting an improvement in memory and learning. They also swam faster during their search for the platform.

Declining muscle strength and loss of muscle tissue (sarcopenia) are common occurrences in aging, partially due to mitochondrial dysfunction [8]. Older mice treated with the new mitochondria saw a huge improvement in their muscle endurance and were able to swim for nearly twice as long as they were able to before the therapy.

Immune System Activity

The immune system also tends to decline as we age. Special immune cells called macrophages, which engulf and destroy foreign particles, pathogens, and malignant cells, become less active. This makes us more susceptible to chronic inflammation, infections, and cancer as we get older.

When the researchers looked at the macrophages of older mice treated with healthy mitochondria, they saw that they were much more active in cleaning up foreign particles. Tests confirmed that the new mitochondria made their way into the macrophages and were responsible for boosting their function.

Conclusion

Mitotherapy may not be the ultimate solution to restore cognitive and muscle functions, as even the older mice who were treated did not perform as well as younger mice on any of the memory, learning, or endurance tests. Reassuringly, there were no reported adverse effects from the therapy. While mitotherapy is still in its infancy and much more research needs to be done, it’s an exciting therapy that shows great promise in helping to counteract the decline in mitochondrial function that we experience as we age.



Literature

[1] Zhao, Z., Yu, Z., Hou, Y., Zhang, L., Fu, A. (2020). Improvement of cognitive and motor performance with mitotherapy in aged mice. Internation Journal of Biological Sciences, 16(5), 848-858.

[2] Druzhyna, N. M., Wilson, G. L, LeDoux, S. P. (2008). Mitochondrial DNA repair in aging and disease. Mechanisms of Ageing and Development, 129(7-8): 383-390.

[3] Cui, H., Kong, Y., Zhang, H. (2012). Oxidative Stress, Mitochondrial Dysfunction, and Aging. Journal of Signal Transduction, 2012: 646354.

[4] Onyango, I. G., Dennis, J., Khan, S.M. (2016). Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies, Aging and Disease, 7(2): 201-214.

[5] Yasuda, K. Khandare, A., Burianovskyy, L., Maruyama, S., Zhang, F., Nasjletti, A., Goligorsky, M. S. (2011). Tunneling nanotubes mediate rescue of prematurely senescent endothelial cells by endothelial progenitors: exchange of lysosomal pool. Aging, 3(6): 597-608.

[6] Shi, X., Bai H., Zhao, M., Li, X., Sun, X. Jiang, H., Fu, A. (2018) Treatment of acetaminophen-induced liver injury with exogenous mitochondria in mice. Translational Research, 196: 31-41.

[7] Fu, A. Shi, X. Zhang, H., Fu, Bin. (2017). Mitotherapy for Fatty Liver by Intravenous Administration of Exogenous Mitochondria in Male Mice. Frontiers in Pharmacology, 8: 241.

[8] Seo, D. Y., Lee, S. R., Kim, N., Ko, K. S., Rhee, B.D., Han, J. (2016) Age-related changes in skeletal muscle mitochondria: the role of exercise. Integrative Medicine Research, 5(3): 182-186.



About the author
Will Hunter

Will Hunter

Will is a professional writer and editor whose main focus and passion is in the field of anti-aging and life extension. He spends a great deal of time searching the scientific literature for the latest longevity research in hopes of finding practical interventions that will slow and even reverse aging. He is also intensely interested in philosophy, finance, and technology and never misses an episode of Jeopardy. Somehow, he still finds time to swim, run, bike, and lift weights.
  1. lillysmon
    March 17, 2020

    Honestly, I would like to be one of the first people to be tested on. Though I’m 16, I like to read about the world making improvements. I want to put more effort to help with changes to the Human Race.

  2. kanakopo
    April 5, 2020

    Excelent

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