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Healthy Aging & the Importance of Building a Better Body Battery

Webinar: “The Renewable Energy Within: Remodeling Mitochondrial Networks through Diet & Lifestyle Strategies” with Kelly Heim, Ph.D.

Associated material: Urolithin A Brochure, FAQs on Urolithin A


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THE CONNECTION BETWEEN MITOCHONDRIA AND HEALTHY AGING

If you think back to your high school biology class, most of us will be able to recall that the mitochondria is considered the powerhouse of the cell. What does that mean in the context of our lives today, and why is understanding the mitochondria important for healthy aging?

It all comes down to energy. Think of optimizing mitochondrial health like installing a renewable battery for your body. All the tasks you will perform today, from sending emails to attending an exercise class, require energy in the form of adenosine triphosphate, or, ATP, which is largely made by the mitochondria. You use at least half of your body weight worth of ATP every day!1

The process of ATP synthesis is complicated, but for a quick overview: glucose, fatty acids, and certain amino acids from our diet are metabolized by the TCA cycle, the Krebs cycle, and glycolysis. These chemical and enzymatic reactions produce NADH, which carries an electron to the electron transport chain, creating a proton gradient which stimulates ATP synthase. This is the enzyme that converts ADP to ATP, which is then used as energy for our cells.

There are hundreds or even thousands of mitochondria performing this task constantly in each cell, and it’s been estimated that about 10% of your body weight is mitochondria.2 This mitochondria workforce is dynamic with a continuous state of turnover, which means it can rapidly adapt to your changing energy demands. For example, ATP output will be low while you are sitting and sending emails but will increase greatly at your exercise class.

As we age the quality and quantity of mitochondria naturally decrease and contribute to something called ‘age-associated cellular decline’. Loss of mitochondrial quality or quantity has been associated with several phenotypes, including loss of gray matter in the brain, fewer cardiomyocytes, slower detoxification, and smaller, weaker muscles.3

On the micro scale, older, damaged mitochondria not only produce less ATP, but they contribute to tissue atrophy, cellular degeneration, and apoptosis.4 These factors contribute to the decline in cellular function that occurs when aging sets in and commonly progresses through the remainder of the lifespan.

SUPPORTING OPTIMAL MITOCHONDRIA HEALTH

While aging is inevitable, there are two key ways you can support your mitochondria through the aging process.

First, increase the formation of mitochondria by activating mitochondrial biogenesis. This process is highly responsive to diet and lifestyle, specifically caloric restriction. Though it may initially seem counterintuitive, eating less calories can boosts ATP levels.5 Other ways to support mitochondrial biogenesis is to increase exercise and consider supplementation with Adiponectin, Resveratrol, Berberine, PQQ, Adenosylcobalamin, and CoQ10.6 It is important to note that the new mitochondria created are still at risk of the effects of aging.‡

The second way is to support mitochondrial health is to promote the removal of the old mitochondria through a process called mitophagy. As they age, mitochondria produce less energy, and may even disturb normal cellular functions as they accumulate. Therefore, cells rely on mitophagy, the process of selective disposal of dysfunctional or superfluous mitochondria and their components, to keep the cellular environment clear for only the best mitochondria possible. Exercise and caloric restriction are also helpful in supporting optimal mitophagy.5,6

Mitophagy, like most things, can decrease with age. Poor mitophagy contributes to fatigue, decreased grip strength, and an increase in age-related neurological changes.8

When working on weight management with your patients, be sure to set reasonable expectations for increasing fiber in their diets.

This lends itself to the question: if we want to optimize healthy aging by supporting healthy mitochondria health, then how can we support mitophagy, which is also affected by aging?



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THE ROLE OF UROLITHIN A

Oral ingestion of urolithin A has been shown to increase mitophagy in preclinical models and improve muscle function and exercise capacity in rodents, and increase muscle strength in C. elegans.9‡

Urolithin A is a metabolite derived from ellagitannins found in pomegranates, nuts, and berries. Urolithins have excellent bioavailability, and can reach very high micromolar levels in plasma, as well as cross the blood brain barrier. However, ellagitannins are complex and require a multi-step breakdown by the microbiome before these metabolites are freely available.10,11 Not all people have the bacteria in their microbiome necessary to fuel this breakdown.12,13 Oral supplementation can be an easier way for their bodies to access this metabolite.

In 2019, Andreux et all performed a clinical trial of oral urolithin A supplementation (500mg, 1000mg per day) on sedentary, elderly adults showed these doses to be safe, bioavailable, and effective in increasing mitochondrial gene expression in skeletal muscle and improved mitochondria biomarker profiles.14‡

Urolithin A is a first-in-class mitophagy modulator for cellular energy & muscle health.‡ Along with exercise, caloric restriction, and an understanding of the importance of mitochondrial renewal, you can support your body battery for years to come.

WORKS CITED

  1. Tornroth-Horsefield, Susanna, and Richard Neutze. “Opening and Closing the Metabolite Gate.” Proceedings of the National Academy of Sciences, vol. 105, no. 50, 2008, pp. 19565–19566.
  2. Lane, N. Power, Sex, Suicide: Mitochondria and the Meaning of Life. Oxford: Oxford University Press, 2005.
  3. Larsson L, Degens H, Li M, et al. Sarcopenia: Aging-Related Loss of Muscle Mass and Function. Physiol Rev. 2019;99(1):427-511. doi:10.1152/physrev.00061.2017
  4. Calvani R, Joseph AM, Adhihetty PJ, et al. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy. Biol Chem. 2013;394(3):393-414. doi:10.1515/hsz-2012-0247
  5. Guan Y, Drake JC, Yan Z. Exerc Sport Sci Rev. 2019 Jul;47(3):151-156. 6.
  6. Mehrabani S, Bagherniya M, Askari G, et al. J Cachexia Sarcopenia Muscle. 2020 Aug 27.
  7. Waltz TB, Fivenson EM, Morevati M, et al. Sarcopenia, Aging and Prospective Interventional Strategies. Curr Med Chem. 2018;25(40):5588-5596.
  8. Sebastian D, et al. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. EMBO J. 2016
  9. Ryu D, et al. Nat Med. 2016 Aug;22(8):879-88.
  10. Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F. Evid Based Complement Alternat Med. 2013;2013:270418.
  11. Heim KC. In: Antioxidant Polymers: Synthesis, Properties, and Applications. Cirillo G, Iemma F, eds. Taylor and Francis, c. 2012.
  12. García-Mantrana I et al. Nutrients. 2019 Oct; 11(10): 2483.
  13. Cortes-Martin A, Garcia-Villalba R, Gonzalez-Sarrias A, et al. Food Funct. 2018, 9:4100-4106.
  14. Andreux PA, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism. June 2019. 1: 595-603