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Researchers at the Salk Institute have published new data showing that a number of Alzheimer’s drug candidates based on the supplements fisetin and curcumin also appear to slow aging in mice.

Targeting aging directly to prevent disease

If old age is the single most significant risk factor for diseases such as Alzheimer’s, then it makes sense that targeting the underlying aging processes has the potential to delay, prevent, or even reverse the disease. This is the focus of researchers working in the field of rejuvenation biotechnology, a branch of aging research that focuses on targeting the aging processes directly in order to combat age-related diseases.

Geroprotectors are substances which have the potential to slow down the rate at which an animal ages by targeting the aging processes. The new study examines a number of compounds and identifies some that protect the neurons from harm by slowing down an aging process; the researchers named these compounds geroneuroprotectors [1].

The team led by Salk Senior Staff Scientist Pamela Maher initially looked at two plant compounds with known medicinal properties: fisetin, a naturally occurring flavonoid found in fruits such as strawberries, and curcumin, an active compound found in the spice turmeric. These compounds are thought to have neuroprotective properties, allowing them to protect the neurons from some of the detrimental effects of aging.

New drugs based on old favorites

By using these compounds as a basis, the researchers created three Alzheimer’s drug candidates called CMS121, CAD31, and J147; they also used fisetin and curcumin directly. The team demonstrated that all five of these compounds reduced biomarkers of aging, increased the median lifespan of mice and flies, and reduced the signs of dementia.

The common link between all five compounds was that they all targeted the same pathways known to extend lifespan in various species. Therefore, all five substances can be classified as geroneuroprotectors due to their common mechanism of action, which involves a slowing of an aging process.

The next step for the research team involves moving the newly created compounds into human clinical trials. CMS121, which is based on fisetin, is currently in the animal toxicology study phase before it progresses into human clinical trials. The researchers did not mention the progress of the curcumin-based CAD31, but J147, which is also based on curcumin, is currently undergoing review before it potentially advances to human trials early in 2019. The researchers also plan to include various biomarkers of aging in these human trials to ascertain any geroprotective effects they might have in people.

The team is also investigating the effects of these geroprotective compounds on other organs and tissues outside the brain to see if they grant similar protective effects. If this is the case, then other kinds of age-related diseases might also be delayed or prevented by targeting the aging processes in the same manner.

Conclusion

Both fisetin and potentially curcumin have been suggested to have senolytic properties, so it is not entirely surprising to see them acting in a geroprotective way [2-3].

It should be noted that curcumin and fisetin were also identified as geroneuroprotectors during this study and are readily available as supplements, so they may provide therapeutic benefits now. The usual caveats apply to people considering taking these compounds; you should follow a science-based approach whenever self-testing, as there is considerable potential for harm if you do not.

It is once again great to see researchers confirming what many of us have been saying for years: that the way to treat age-related diseases is to treat the underlying damage that aging causes and repair it. Geroprotectors are a step towards doing that, and once effective therapies start to arrive and cure the previously incurable, everyone might get behind the idea of doing something about aging.

Literature

[1] Schubert, D., Currais, A., Goldberg, J., Finley, K., Petrascheck, M., & Maher, P. (2018). Geroneuroprotectors: Effective Geroprotectors for the Brain. Trends in Pharmacological Sciences.

[2] Fuhrmann-Stroissnigg, H., Ling, Y. Y., Zhao, J., McGowan, S. J., Zhu, Y., Brooks, R. W., … & Corbo, L. (2017). Identification of HSP90 inhibitors as a novel class of senolytics. Nature communications, 8(1), 422.

[3] Yousefzadeh, M. J., Zhu, Y., McGowan, S. J., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., … & McGuckian, C. (2018). Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 36, 18-28.

About the author

Steve Hill

As a scientific writer and a devoted advocate of healthy longevity and the technologies to promote them, Steve has provided the community with hundreds of educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).
  1. November 19, 2018

    Good find. I’ve been chatting with these PIs lately about drug development. The fisetin derivatives are quite interesting, J147 is already on the way to the clinic next year. Finally an Alzheimer’s drug that does not depend upon the Amyloid hypothesis.

  2. November 19, 2018

    Kirkland from the Mayo Clinic also has a clinical study on fisetin which is already in phase 2 and has been started in February. It’s not advertized as a senolytic study but if you read the description you know what it is. The final results are expected in mid 2020.
    https://clinicaltrials.gov/ct2/show/NCT03430037

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