Help us: Donate
Follow us on:
×

Avoiding Osteoporosis with Alpha-Ketoglutarate

This well-known supplement may be able to fight age-related bone loss.

Osteoporosis HipOsteoporosis Hip

Research on rodents shows that alpha-ketoglutarate could be an effective way to treat or even prevent osteoporosis [1].

Feeling frail

Osteoporosis increases the risk of bone fractures in older people, harming them as individuals and increasing the load on hospitals as the average age of the population rises. Finding ways to prevent bones from weakening with age is thus important for vulnerable people and for the healthcare system in general.

Earlier studies have offered hope that alpha-ketoglutarate (αKG) might prevent bone loss or strengthen weakened bones. Experiments showed that αKG promotes bone development in rats and lambs [2, 3], and it also delays the decline of rapid, coordinated movement in worms [4]. In addition, αKG was shown to have a key role in maintaining the ability of embryonic stem cells to differentiate into any cell type [5]. Based on this, αKG seems like a promising candidate for preventing or repairing osteoporosis, but there haven’t been experiments testing the idea.

Bringing back toughness

A team of researchers in China and the US tested how αKG affects bone mass, bone loss, and healing in mice and rats. They dosed old rodents with two concentrations of αKG in their drinking water and then measured the volume, thickness, and mass of various bones. They found that αKG treatment increased bone mass and density, and they also showed that the treated mice had more osteoblasts and osteoclasts, cells that make and break down bone material. In cell cultures, mesenchymal stem cells, which produce osteoblasts and osteoclasts, from the αKG-treated mice had more osteogenic potential and higher expression of osteogenic genes.

Having shown that αKG can increase bone mass in older rodents, the team then tested whether it could prevent bone loss. They treated adult mice with αKG and found that they lost less bone mass over the next few months than a control group did. Finally, experiments with a “drilling-hole injury” showed that αKG improves bone healing in older rats.

The researchers did some molecular analyses to figure out how αKG boost stem cells to keep bone healthy. They discovered that αKG treatment reduces the levels of certain types of methylation in the stem cells of older mice, leading to increased expression of key bone development genes.

Age-related osteoporosis is characterized by the deterioration in bone volume and strength, partly due to the dysfunction of bone marrow mesenchymal stromal/stem cells (MSCs) during aging. Alpha-ketoglutarate (αKG) is an essential intermediate in the tricarboxylic acid (TCA) cycle. Studies have revealed that αKG extends the lifespan of worms and maintains the pluripotency of embryonic stem cells (ESCs). Here, we show that the administration of αKG increases the bone mass of aged mice, attenuates age-related bone loss, and accelerates bone regeneration of aged rodents. αKG ameliorates the senescence-associated (SA) phenotypes of bone marrow MSCs derived from aged mice, as well as promoting their proliferation, colony formation, migration, and osteogenic potential. Mechanistically, αKG decreases the accumulations of H3K9me3 and H3K27me3, and subsequently upregulates BMP signaling and Nanog expression. Collectively, our findings illuminate the role of αKG in rejuvenating MSCs and ameliorating age-related osteoporosis, with a promising therapeutic potential in age-related diseases.

Conclusion

While this is obviously just a first step, it’s still quite encouraging research. Whether or not αKG ever passes muster and makes it through clinical trials to become an osteoporosis treatment, it will at least serve as a powerful tool to unravel the factors involved. Addressing the burdens of aging will probably involve a variety of treatments to adjust the behavior of a range of different pathways, and αKG seems well positioned to help us tackle issues in bone development and stem cell regulation.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. We are committed to responsible journalism, free from commercial or political influence, that allows you to make informed decisions about your future health.

All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future. You can support us by making a donation or in other ways at no cost to you.

Vitalik Buterin Exclusive Interview: Longevity, AI and More

Vitalik Buterin holding Zuzu, the puppy rescued by people of Zuzalu. Photo: Michelle Iai Don’t try finding Zuzalu on a...

Centenarians Have Slightly Different Gut Ecologies

Researchers publishing in Nature Microbiology have determined that the viruses populating the intestines of centenarians are slightly different from those...

Hypoxia Extends Median Lifespan in Fast-Aging Mice by 50%

Scientists have found that continuous oxygen restriction drastically extends the lifespan of progeroid mice, but the effect's mechanism remains a...

Discovering Why Adrenal Cancer Is More Dangerous for Women

A paper published today in Nature Aging has explained a relationship between cellular senescence, cancer of the adrenal glands, and...

Literature

[1] Wang, Y., Deng, P., Liu, Y., Wu, Y., Chen, Y., Guo, Y., … & Li, Q. (2020). Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations. Nature communications, 11(1), 1-14.

[2] Dobrowolski, P., Tomaszewska, E., Bienko, M., Radzki, R. P., & Pierzynowski, S. G. (2013). The effect of dietary administration of 2-oxoglutaric acid on the cartilage and bone of growing rats. British journal of nutrition, 110(4), 651-658.

[3] Harrison, A. P., Tygesen, M. P., Sawa-Wojtanowicz, B., Husted, S., & Tatara, M. R. (2004). α-Ketoglutarate treatment early in postnatal life improves bone density in lambs at slaughter. Bone, 35(1), 204-209.

[4] Chin, R. M., Fu, X., Pai, M. Y., Vergnes, L., Hwang, H., Deng, G., … & Hu, E. (2014). The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature, 510(7505), 397-401.

[5] Carey, B. W., Finley, L. W., Cross, J. R., Allis, C. D., & Thompson, C. B. (2015). Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature, 518(7539), 413-416.

CategoryNews
About the author

Sedeer el-Showk

Sedeer became a professional science writer after finishing a degree in biology. He also writes poetry and sff, and somehow juggles an ever-growing list of hobbies from programming to knitting to gardening. Eternal curiosity and good fortune have taken him to many parts of the world, but he’s settled in Helsinki, Finland for the moment. He hopes he’ll never stop learning new things.
No Comments
Write a comment:

*

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.