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Senolytic compounds hold promise to reverse aging in humans. In a review published yesterday, leading researcher James L. Kirkland, M.D., Ph.D., compiles a comprehensive list of the leading senolytic compounds under development for human use, two of which are currently in clinical trials. [This article first appeared on LongevityFacts.com. Follow us on Reddit | Google+. Author: Brady Hartman. ]

Imagine if you were able to reverse aging and bring your body back to its original health and vigor.

Researchers have already discovered a group of drugs called senolytics which perform this miraculous transformation in mice and are testing them in humans as we speak.

The research holds promise that we may not have to suffer from the ill health of old age.

Yesterday, Mayo Clinic researcher James L. Kirkland, M.D., Ph.D., published a review of these senolytic drugs and explained the rationale behind each compound as a potential anti-aging treatment.

Dr. Kirkland knows a thing or two about aging and is considered a leader in the field of geroscience and a pioneer in the field of senolytic development. Dr. Kirkland shows his enthusiasm for senolytics, saying,

“The emerging repertoire of senolytic drugs shows that they are having an impact on a huge range of diseases,” adding “Our goal is to achieve the same success in humans as we have in preclinical animal models in efforts to prevent or delay the conditions associated with aging.”

What Are Senolytics?

Our bodies are home to damaged cells called senescent cells, also known as zombie cells. All of us have senescent cells, beginning in our youth. One of the Hallmarks of Aging is that these damaged cells build up naturally as we age and cause chronic inflammation and disease. Senescent cells are the walking dead of our organs and generate a low-level persistent inflammation known as inflammaging. Zombie cells are suspected to cause many of the chronic diseases of aging such as arthritis, type 2 diabetes, heart disease, aging skin, and perhaps even cancer.

Anti-aging proponents such as Aubrey de Grey of the SENS Research Foundation and other lifespan extension enthusiasts have been long advocating for ways to remove these troublemakers.

Senolytic drugs are compounds which clear these senescent cells from our bodies and they have demonstrated remarkable results.

Elderly mice treated with senolytic compounds had more energy and appeared more youthful and were able to run twice as far as untreated mice. Treatment with the senolytic compound improved their kidney function and regrew their fur.

What Causes Senescent Cells?

Over the decades a variety of hazards attack our cells, including toxins and radiation. As well, our cells have a limited warranty, in that they divide about 50 times, their telomeres shortening with each division. When a cell has reached the end of its useful life, it is programmed to self-destruct in called apoptosis. Unfortunately, some of these non-functional cells refuse to commit suicide. The body’s immune system clears out many of these holdouts, however, are immune function weakens with age, causing increasing numbers of these zombie cells to build up. Senescent cells don’t just sit around idly. Instead, they wreak havoc throughout our bodies, by churning out buckets of inflammation-producing compounds and releasing them into our tissues and bloodstream.

Senescent Cells Cause Chronic Inflammation

As these senescent cells build up in our tissues, they contribute to the chronic conditions of aging. Not only do they produce chronic inflammation, but they also accelerate conditions such as atherosclerosis, arthritis, cancer and other diseases of aging. As Dr. Kirkland states in his recent review,

“The biological processes that underlie aging phenotypes and are active at the nidus of most chronic diseases include chronic, low-grade, ‘sterile’ (absence of known pathogens) inflammation.”

And what happens when we remove these senescent cells from our bodies?

Dr. Kirkland provides us with the answer, adding:

“reducing senescent cell burden can lead to less inflammation.”

Seduce Healthy Cells

As if that wasn’t bad enough, the pro-inflammatory compounds emitted by senescent cells also encourage nearby cells to become senescent as well.

Like zombies, senescent cells induce their perfectly healthy neighbors to convert into troublemakers. This causes the aging process to accelerate with each passing year.

Senolytics are the only thing that science has to stop this downward spiral. Senolytic compounds kill these zombie cells and reverse the toll they take on the body and their contribution to the aging process.

Kirkland’s Review of Senolytics

In his recent review, Dr. Kirkland states that senolytics have the potential to revolutionize medicine in the near future. The leading anti-aging researcher says

“The introduction of effective senolytics or other agents that target fundamental aging processes into clinical practice could be transformative.”

The Mayo Clinic researcher is keen to speed up the development and arrival of senolytic therapies, pointing out their tremendous potential, when he states that

“These drugs may be critical to increasing health span and delaying, preventing, or alleviating the multiple chronic diseases that account for the bulk of morbidity, mortality, and health costs in developed and developing societies. “

Dr. Kirkland shows the potential for senolytics to prevent many conditions that plague us as we age, including frailty and cognitive decline, when he adds,

“They [senolytic compounds] could also delay or treat the geriatric syndromes, including sarcopenia, frailty, immobility, and cognitive impairment, as well as age-related loss of physiological resilience, in a way not imaginable until recently.“

Dr. Kirkland added that senolytics hold the potential to be a universal anti-aging treatment. Rather than preventing the diseases of aging one-by-one, a single medicine could potentially prevent or delay them all, when he adds,

“These [senolytic] agents could transform geriatric medicine from being a discipline focused mainly on tertiary or quaternary prevention into one with important primary preventive options centered on a solid science foundation equivalent to, or even better than, that of other medical specialties.”

The Mayo Clinic researcher identified a list of the most well-known senolytic compounds, including Dasatinib, Navitoclax (ABT-263), Piperlongumine, Quercetin and the FOXO4-DRI peptide. As well, Dr. Kirkland listed newer senolytic compounds, such as alvespimycin (17-DMAG), tanespimycin (17-AAG), A1331852, A1155463, Fisetin, and Geldanamycin.

The above list is not all-inclusive, as Dr. Kirkland points out with the statement, “Yet more senolytics are in development.”

Kirkland noted that all of these listed compounds were shown to kill senescent cells on live cells in a test tube. But the test tube environment is far different than a living organism. Of the senolytics identified thus far, only Navitoclax, Dasantib combined with Quercetin, the FOXO4-DRI peptide, and alvespimycin (17-DMAG) have been shown to clear senescent cells in living organisms, typically in mice. As the Mayo Clinic researcher noted in his review, “Several senolytics, including dasatinib plus quercetin, navitoclax, 17-DMAG, and a peptide that targets the BCL-2- and p53-related SCAPs, have been demonstrated to be effective in reducing senescent cell burden in mice, with decreases in cellular senescence–associated β-galactosidase activity; p16Ink4a+ cells; p16Ink4a, p21Cip1, and SASP factor messenger RNA; telomere-associated foci; and other senescent cell indicators.”

Dr. Kirkland added that senolytics need not be taken daily, but only periodically, adding,

“Senolytics do not have to be continuously present to exert their effect. Brief disruption of pro-survival pathways is adequate to kill senescent cells. Thus, senolytics can be effective when administered intermittently. For example, dasatinib and quercetin have an elimination half-life of a few hours, yet a single short course alleviates effects of leg radiation for at least 7 months.”

The advantages of periodic dosing are substantial, as the Mayo Clinic researcher points out,

“Advantages of intermittent administration include less opportunity to develop side effects, the feasibility of administering senolytic drugs during periods of relatively good health, and less risk of off-target effects caused by continuous exposure to drugs.”

Dr. Kirkland shows the potential for senolytics to transform medicine from the current emphasis on of treating the conditions of aging one-by-one and instead treating aging as a single disease when he adds that “Senolytics might prevent or delay chronic diseases as a group, instead of one at a time in presymptomatic or at-risk individuals.“

As Dr. Kirkland reveals in his review, the medical field is shifting from the traditional approach of treating the ailments of aging one-by-one and instead treating aging as a single disease.

Furthermore, the Mayo clinic researcher holds high hopes for these senolytic compounds, especially those that have been tested in live animals, such as the FOXO4-DRI peptide, Dasantib combined with Quercetin, alvespimycin (17-DMAG) and Navitoclax, adding,

“… if what can be achieved in preclinical aging animal models can be achieved in humans, it may be feasible to alleviate dysfunction even in frail individuals with multiple comorbidities, a group that until recently was felt to be beyond the point of treatment other than palliative and supportive measures.”

Senolytic compounds are experimental drugs and have not been proven to be effective nor safe in clinical trials on humans. Experimental drugs carry a much higher risk than FDA-approved drugs, as Dr. Kirkland points out

“Considerable care must be taken, particularly until clinical trials are completed, and the potential adverse effects of senolytic drugs are understood fully, it is conceivable that the rapidly emerging repertoire of senolytic agents might transform medicine as we know it.”

We might not have to wait long; researchers are currently conducting a clinical trial to test two of the senolytic compounds in patients with brain tumors. More trials are in the works.

The Great Senolytics Race

All over the world scientists are in a race to bring senolytics to the clinic. The field has heated up in the past several years, with some groups approaching the problem of aging from different angles. Many firms have been started to commercialize senolytics, with the startup Unity Biotechnology leading the pack. Unity plans to have a senolytic drug in human clinical trials by the end of this year.

Mayo Clinic plans to conduct clinical trials with a senolytic compound of their own. Other companies, including Oisin Biotechnologies, are hot on the heels of Unity, furthering adding to the race to be the first to bring one of the candidate senolytic compounds to market.

Assuming one of these organizations brings a compound to market, senolytics will be the world’s first rejuvenation technology.

Bottom Line

Senolytics are the leading lifespan-extending therapy, a class which includes the diabetes drug metformin, now being tested as an anti-aging drug in clinical trials. Other anti-aging interventions are also under development, such as telomere therapy, calorie restriction and the Fasting Mimicking Diet, and the lifespan-extending drug rapamycin.

Anti-aging compounds called senolytics have the potential to reverse aging in humans.

Scientists have identified several senolytic compounds which reverse aging in mice; this list includes Dasantib combined with Quercetin, Navitoclax, the FOXO4-DRI peptide, and alvespimycin (17-DMAG). Other senolytics have only been shown to work in the test tube.

Many groups are working to bring an effective senolytic to the clinic. None of these compounds have been tested in clinical trials, with two trials currently underway.

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References

Cover photo: Getty Images.

James Kirkland, T. Tchkonia, Y. Zhu, L. Niedernhofer, and D. Robbins. The Clinical Potential of Senolytic Drugs. (2017). Journal of the American Geriatrics Society. DOI: 10.1111/jgs.14969. Available Online.

Carlos López-Otín, M. A. Blasco, L. Partridge, M. Serrano, and G. Kroemer.The Hallmarks of Aging. (2013). Cell, 153(6), 1194-1217. Available Online.

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Jan M. van Deursen. The role of senescent cells in ageing. Nature. May 22, 2014; 509(7501): 439–446. Available Online.

Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., & O’Hara, S. P. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. (2015). Aging Cell, 14(4), 644-658.

Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., Van De Sluis, B. and van Deursen, J. M. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. (2011). Nature, 479(7372), 232-236.

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Disclaimer

Diagnosis, Advice, and Treatment: This article is intended for informational and educational purposes only and is not a substitute for professional medical advice. Senolytic compounds are experimental drugs and have not been proven to be safe and effective in clinical trials. Experimental drugs such as senolytics carry a much higher risk than FDA-approved drugs. The information provided in this report should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. Consult a licensed physician for the diagnosis and treatment of any and all medical conditions. Call 911, or the equivalent emergency hotline number, for all medical emergencies. As well, consult a licensed physician before changing your diet, supplement or exercise programs. Photos, External Links & Endorsements: This article is not intended to endorse companies, organizations or products. Links to external websites, depiction/mention of company names or brands, are intended only for illustration and do not constitute endorsements.