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Pomegranate-derived Compound Reverses Signs of Aging in Mice

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Review of “Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents” from Nature Medicine by Stuart P. Atkinson

Headlines often boast of a new super-food, a new detox compound, or a new supplement which promises to boost your health, enhance your standard of living, and maybe even boost your lifespan by a few extra weeks. It all sounds too good to be true, and, as expected, almost all these headlines turn out to be bunk. 

However, recent research has suggested that a pomegranate-derived compound [1] may actually represent an exciting means to retard age-related decline in some bodily functions. 

The pomegranate-derived compounds under scrutiny in a new Nature Medicine study are the ellagitannins (ETs) [2] which are metabolized into 4 different compounds called urolithins (UA, UB, UC and UD). This research, led by Chris Rinsch and Johan Auwerx (Ecole Polytechnique Fédérale de Lausanne, Switzerland) now shows that urolithins have the potential to reverses signs of aging using a number of model animal systems [3]. 

The initial part of the study concentrated on responses in C. elegans, finding that UA mediated an extension of lifespan and improved worm activity, both dependent on mitochondrial function. In detail, short-term UA treatment maintained maximal respiratory capacity but led to lower mitochondrial content in intestinal and muscle cells caused by an increase in the autophagy of mitochondria (mitophagy) [4]. This seems counterintuitive; however, the removal of age-dependent accumulations of aberrant mitochondria from intestinal/muscle cells [5] may allow the proliferation of normal mitochondria, so allowing the worm to optimize cellular mitochondrial activity. In agreement with this hypothesis, the study also found mitochondrial levels comparable or higher than controls in long-term UA treated worms, suggesting that UA activated mitochondrial biogenesis in older worms.

So can this pomegranate-derived compound reverses signs of aging in mammals? UA treatment of cultured mouse myoblast and intestinal cells also stimulated mitophagy, while model mice showing signs of obesity- and age- related muscle decline robustly increased muscle function in response to UA. However, UA treatment also increased muscle function in young mice also, with some signs of an increase in mitophagic function observed.

An incredible finding......now what next for this pomegranate-derived compound? If we can combine an increase in mitophagy and an increase in mitochondrial biogenesis, can we further boost this effect? Can we translate these findings quickly to the clinic to treat the elderly, alone or in combination with other interesting therapeutic interventions, whose decline in muscle function significantly reduces mobility and, therefore, quality of life? Could reversing the signs of aging in humans be as simple as a nutritional supplementation with this pomegranate-derived compound?

References

  1. Johanningsmeier SD and Harris GK Pomegranate as a functional food and nutraceutical source. Annu Rev Food Sci Technol 2011;2:181-201.
  2. Bakkalbasi E, Mentes O, and Artik N Food ellagitannins-occurrence, effects of processing and storage. Crit Rev Food Sci Nutr 2009;49:283-298.
  3. Ryu D, Mouchiroud L, Andreux PA, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med 2016;22:879-888.
  4. Youle RJ and Narendra DP Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2011;12:9-14.
  5. Bratic A and Larsson NG The role of mitochondria in aging. J Clin Invest 2013;123:951-957.