Why Do We Accumulate Senescent Cells Anyway?

One component of aging is the damage caused by senescent cells, those that have stopped dividing, have not destroyed themselves in a form of programmed cell death or otherwise been removed from the picture, and have started to do a variety of things that are harmful to surrounding cells over time. Removal of senescent cells, say by adapting one of the many flexible and precise cell killing technologies being developed in the cancer research community, is one of the line items in the Strategies for Engineered Negligible Senescence:

So-called 'senescent' cells are those that have lost the ability to reproduce themselves. They appear to accumulate in quite large numbers in just one tissue (the cartilage in our joints), but even in these small numbers they appear to pose a disproportionate threat to the surrounding, healthy tissues, because of their abnormal metabolic state. Senescent cells secrete abnormally large amounts of some proteins that are harmful to their neighbours, stimulating excessive growth and degrading normal tissue architecture. These changes appear to promote the progression of cancer.

Why do senescent cells accumulate with age? And accumulate they do:

the Brown team began to study aging animals - baboons living on a research preserve that ranged in age from 5 to 30. In human years, that age range is roughly 15 to 90. ... For replicative senescence, the most important biomarker is telomere dysfunction-induced foci, or TIFs. Presence of these structures signals that the protective chromosome caps called telomeres have dwindled enough to halt cell division. ... What they found: The number of senescent cells increased exponentially with age. TIF-positive cells made up about 4 percent of the connective tissue cell population in 5-year-olds. In 30-year-olds, that number rose as high as 20 percent.

Over at Ageing Research, some thoughts on the matter:

If the accumulation of senescent cells are so detrimental to the tissues in which they reside, why haven't we evolved mechanisms to remove them? The answer is that we probably have, but the mechanism which removes them from the tissues becomes impaired as with age.


One possibility is that senescent cells are removed by the immune system. Senescent cells secrete cytokines to attract immune cells to their location (for their removal), secrete matrix degrading proteins to allow the immune cells easy access and secrete growth factors to stimulate the proliferation of surrounding cells for its replacement once the cell is removed. However, since the immune system itself is governed by ageing mechanisms, its ability to remove senescent cells gradually decreases, therefore the accumulation of senescent cells gradually increases.

Which is plausible, and those unremoved senescent cells sit there releasing biochemicals that damage and misdirect cells in the surrounding tissue. The aging immune system has a lot to answer for already, in terms of the damage done due to its decline, and it wouldn't surprise me to see more items added to the list.

UPDATE 11/2011: You might also take a look at a more recent study that makes for a compelling demonstration of the merits of destroying senescent cells:

Scientists at the Mayo Clinic, in the US, devised a way to kill all senescent cells in [mice genetically engineered to age more rapidly than normal, and therefore accumulate senescent cells more rapidly than normal]. ... when they were given a drug, the senescent cells would die. The researchers looked at three symptoms of old age: formation of cataracts in the eye; the wasting away of muscle tissue; and the loss of fat deposits under the skin, which keep it smooth. Researchers said the onset of these symptoms was "dramatically delayed" when the animals were treated with the drug. When it was given after the mice had been allowed to age, there was an improvement in muscle function.

UPDATE 03/2015: There is now a more recent overview of senescent cells in aging here at Fight Aging! In addition, the state of the science continues to advance. Researchers recently demonstrated improved health in normal aged mice via partial clearance of senescent cells in some tissues using a combination of existing drugs:

The scientists coined the term "senolytics" for the new class of drugs. "We view this study as a big, first step toward developing treatments that can be given safely to patients to extend healthspan or to treat age-related diseases and disorders. When senolytic agents, like the combination we identified, are used clinically, the results could be transformative. The prototypes of these senolytic agents have more than proven their ability to alleviate multiple characteristics associated with aging. It may eventually become feasible to delay, prevent, alleviate or even reverse multiple chronic diseases and disabilities as a group, instead of just one at a time."

I have been doing research on cleansing the body.I have found that cleansing the body of toxins is highly recommended by natural healing doctors.These toxins build up in our bodies and they will eventually cause fatigue,autoimmune diseases,and at worst cause cancers and other deadly diseases.I'm wondering....Wouldn't it be easier to recommend that we do whole body cleanses to rid our bodies of these toxins that are causing these debilitating illnesses?A person can cleanse with basic all natural products that you can purchase at an organic market.This would make us all healthier and help slow the aging process.

Posted by: Stacia at November 6th, 2011 11:30 PM

What are the drugs that target and kill senescent cells ?
How safe are they ?
Are they available ?

Posted by: fred smith at November 7th, 2011 3:03 PM

I'm not surprised they are not eliminated because the energy budget is limited to insure reproduction, not to insure efficiency during life after reproduction nor that it will be painless or inefficient. What happens then is almost a toss of the dice. What is certain is maintaining internal constancy will be reduced and the organism; that is, the host soma will deteriorate and die.

Posted by: Hank Roth at January 30th, 2012 10:22 AM

This analogy has helped devise a strategy which i am hopeful will help rid me of senescent cells (probably not original - can't remember where I may have read this):

Think of a business during a growth/boom phase. Mediocre, semi-productive workers may accumulate over time as there is little pressure to increase efficiency. When times get tough and management starts talking layoffs, workers are more critically assessed and the less productive ones are often the first to be laid off.

Our body is the corporation and our food saturated environment provides the boom time and the senescent cells are the low productivity workers. The key to getting rid of them is to artificially put the body under stress for efficiency. This can be done with fasting. Look up 'fasting autophagy'. How mu h, how often are unclear for maximum benefit.

Posted by: Peter Andrews at December 12th, 2012 7:16 AM

Is anyone researching a combined strategy of removing senescent cells and then growing new cells using bioidentical stem cells harvested from fat tissue or bone marrow. Services are available for storing such stem cells for years. I would like to store stem cells and then use them as needed as senescent cells are removed. Is this being done or researched?

Posted by: Ernest Edmundson at August 10th, 2013 2:16 PM

Is anyone researching the use of bioidentical stem cells harvested from fatty tissue or bone marrow to repair brain damage caused by water on the brain or just to replace neurons lost from aging?

Posted by: Ernest Edmundson at August 10th, 2013 2:19 PM

Thanks for the very detailed information. What specific body cleansing systems were you referring
To. Thanks Michael

Posted by: J Michael Caldwell at April 30th, 2014 10:06 AM

Notice that in almost three years, no one connected to this ANONYMOUS article has answered any of the several questions?

Posted by: Steve Garcia at August 10th, 2014 2:38 AM

@Steve - Not sure if you are just trolling, but this is a blog, not Yahoo answers, or a web forum where people can entertain themselves arguing points with strangers. You can use google to answer most of the more reasonable questions (a google search of this site with the keyword senescent would already answer most of them). Type "site:fightaging.org senescent" into your search bar/address bar to do this.

Posted by: Jim at November 2nd, 2014 10:31 AM

fascination. love the the thoughts.

Posted by: steve tebon at February 10th, 2016 4:16 PM

Been talking about this for quite a while. Come on Campisi I'm rooting for ya.

Posted by: Matt at February 27th, 2021 5:24 PM
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