Aiming to Remove the Senescent Cell Contribution to Aging and Age-Related Disease

As the years pass ever more of your cells fall into a state of senescence. This is a response to the age of the cell itself, its internal damage, surrounding levels of metabolic waste, the presence of cell-damaging toxins, or other signals that indicate a potentially raised risk of cancer. Senescent cells do not divide or do much else to support the tissue they are a part of, but rather emit a range of potentially harmful chemical signals that encourage other nearby cells to also enter a senescent state. Senescent cells sometimes self-destruct, or they can be removed by the immune system, but the immune system has its own process of age-related decline and this activity falters. Cellular senescence can indeed reduce the risk of cancer, but by the time there are significant numbers of senescent cells gathered in the body their presence causes all sorts of harm: they degrade tissue function, increase levels of chronic inflammation, and can even eventually raise the risk of cancer due to their generally bad behavior.

Cellular senescence is one of the more exciting areas of the biochemistry of aging, because the research community is very close to being able to produce treatments for the targeted, safe removal of senescent cells. Early animal studies have provided initial evidence that doing so does produce improvements in health and longevity, as expected. Further studies in rodents presently in progress should firmly demonstrate that healthy, normal animals benefit from the removal of senescent cells. After that, it is a matter of pulling together the targeted cell killing techniques pioneered by the cancer research community with one of the new prospective methods for accurately distinguishing senescent cells from their healthy peers. If not for the generally slow, expensive pace of medical regulation this is something that could probably be done within the next five years, or much sooner for technology demonstrations in laboratory animals.

Targeted destruction of senescent cells is an excellent candidate for a treatment that, like early stem cell therapies, could be offered outside the US for years prior to the more formal and straitjacketed medical development community coming to the point of trials. All the prototype parts of the toolkit are nearly ready, and a successful treatment to remove unwanted senescent cells would be an unalloyed benefit for any healthy older adult. Sadly, as is the case for near all of the most important areas of longevity science, there is little interest or funding for this work in comparison to its potential benefits to health. Things are moving more rapidly than for many other important areas of aging research, but funding is still at disappointingly low levels. We can hope that this will change at the point at which it becomes viable to offer prototype clinical treatments via medical tourism, in much the same way as matters proceeded for the development of the first stem cell therapies.

Here is the latest in a series of essays on the details of the SENS vision for rejuvenation therapies penned by philanthropist Jason Hope. Hope is one of the more noteworthy donors to the SENS Research Foundation, and clearly believes in the goals he supports:

Death Resistant Cells

There are two main approaches to the problems associated with senescent cells: develop a drug that is toxic to abnormal cells but harmless to healthy ones, or stimulate an immune response that targets and selectively kills unhealthy cells.

Molecules lining the surface of cells help those cells interact with their surroundings; these molecules are to varying degrees distinctive to their fate. Because each type of cell has different surface molecules, these molecules can serve as markers, or identification for that cell. Liver cells have a different group of molecules on their surface than blood cells, for example.

Abnormal cells have abnormal surface molecules, making these cells easy to target for therapy. Oncologists already use this type of approach when treating some types of cancer with the intent of shutting down the cancer cells' growth with drugs or by stimulating the immune system to do the job. In some cases, killing abnormal cells deters, treats, or prevents illnesses by making room for new, healthy cells.

Using SENS Research Foundation funding, scientists from University of Arizona are investigating ways to restore a healthy immune system in aging mice by purging unhealthy immune cells known as "anergic T-cells" to free up space for new and healthy killer T-cells. The researchers also hope to bolster the immune system by increasing the body's ability to produce new killer T-cells.

With funding from SENS Research Foundation and working in Dr. Judith Campisi's laboratory at the Buck Institute for Research on Aging, PhD candidate Kevin Perrott is investigating how molecules affect one type of senescent skin cell to understand its role in inflammation and the immune system. These scientists also hope to discover how to kill these senescent cells before they can cause a problem. Additionally, these researchers are testing a library of compounds to identify any that are capable of selectively targeting senescent cells.

SENS Research Foundation funding also supports research performed by Nick Schaum in the Campisi lab, which has shed light on the link between the two hallmarks of cell senescence, identifying a key driver of inflammation and halted cell division.

The goal of these research projects is to understand how cell programming can cause illness and to develop ways to control cell senescence, either through therapeutic drugs or by stimulating the immune system so that it destroys only abnormal cells while leaving healthy cells intact. Success will lead to new rejuvenation biotechnologies to prevent, treat, and even reverse the course of the disease and disability caused by these abnormal cells.


I'm hoping that someone manages to safely remove senescent cells in a mouse soon using a technique applicable to adult humans. This technology may then perhaps get picked up by a big pharma company or biotech like sirtuins did.

Posted by: jim at July 11th, 2014 10:10 AM

I propose to create a drug (selective "neoBotox") that would selectively destroy the old cells in vivo (to make way for young or rejuvenated stem cells). For example, senescence-associated β galactosidase substrate, which, under the influence of this enzyme, will release the potent toxin. Such a selective toxin would be useful for the rapid elimination from the body of old cells which are the source of aging niche components. At low concentrations of the drug or target delivery (eg, by exosomes with selective receptors to aged cell) into the cell it should not damage the cells with low concentrations of senescence-associated β galactosidase, but will destroy the cells with high concentrations of it.

Posted by: Dmitry Dzhagarov at July 13th, 2014 3:07 AM

Существует такое направление в онкотерапии - онкотропные и онколитические вирусы.
А что, если попытаться получить сенотропные и сенолитические вирусы?

Posted by: Зиновий Белкин at April 16th, 2015 9:24 AM

I know a guy who is 50 years old but looks like he is 25. His skin is young looking and wrinkle free. Why don't longevity scientists search for these types of people and find out what genetics or biochemistry enables such longevity characteristics in skin to exist in some people. I think it would be a worthy line of investigation.

Posted by: Biotechy at September 25th, 2017 3:37 PM

as we wait for a solution, I'm assuming regularly donating blood will remove some percentage of the senescent cells - replacing them with new healthy ones, but generally this can only be done less than 10 / year. something is better than nothing, plus you help others in need.....

Posted by: dxpaap at June 13th, 2019 8:42 PM

check out spermidine supplementation

Posted by: michael j yaros at June 22nd, 2019 11:59 AM

And now we have FOXO4-DRI

Posted by: Jared Young at September 5th, 2020 12:43 PM

I just wonder to what degree a 5 day fast can slough off senescent cells? Is it possible that fasting 5 days out of each month for a year could slough off as many senescent cells as 3 cycles of Dasatinib + Quercetin?

Posted by: Chuck Frasher at April 4th, 2021 8:32 PM

Perhaps we should take Dasatinib + Quercetin + Fisetin and just have one meal a day.

Posted by: Tj Green at April 29th, 2021 4:04 AM

Has this anything to do with EOE? I have foreign cells lining my esophagus. Looking for relief.

Posted by: Carol Quinn Cowels at March 20th, 2022 5:17 PM

Fisetin - from strawberries. Its not cheap, but might not need to take all the time either

Posted by: Jeff at July 29th, 2022 9:32 PM

Cellular senescence is a or the major cause of aging and it occurs as the chromosomes in each cell reach their telomere limit. At the telomere limit, cells either under apoptosis or become senescent and highly inflammatory. The choice of which pathway is largely genetic but apoptosis can be promoted at the telomere limit by several foods that include
ANTHOCYANINS (red, purple, blue & black berries)
RESVERATROL (Raspberries, Blueberries, Red Wine)
CURCUMIN (Turmeric)
LYCOPENE (Guava, Tomato, Watermelon, Grapefruit, Papaya, Red peppers)
GENISTEIN (Soy - based foods)
APIGENIN (Parsley, Chamomile, Celery, Oregano)
The inflammation in senescent cells can be greatly reduced by Oleic Acid, which (in Olive Oil) is possibly the key component of the Mediterranean diet.

Posted by: Judy Ford at February 21st, 2023 6:35 PM

You can see how it has affected the people of the Mediterranean, a healthy and happy old age. Curious as to whether it would change the number of senescent cells in their offspring over the generations in many years, possibly driving them out completely. Think about many many years ago biblically humans lived well beyond 100 something happened to change this radically, Diet would play a major role, and now with science the way it is. I would like to think that now and in the future we would have found a way to cure and or prevent all cancers!!! But then I remember how much money can be made from the sick and dying and as sad as that is. It's the truth! Until we recognize that love rules the world and not money we will continue to lose our loved ones to the big C and more!!!!

Posted by: Donna Naylor at June 27th, 2023 3:32 AM
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