Is It Safe to Kill Off Our Senescent Cells?

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by Nils Osmar. December 15, 2021

I’m currently fasting every Sunday and Thursday. Today’s Sunday, so I’ll be taking a break from eating.

I had coffee in the morning because coffee promotes autophagy (so I don’t view it as breaking my fast). (Opinions differ about what breaks a fast, of course.)

I may fast till tomorrow morning (making it a 36 or 40 hour fast, depending on what time I have breakfast), or I may just skip breakfast and lunch today and have dinner tonight around 6 pm, making it a 24 hour fast, since my last meal was last night at 6 pm.

Taking Quercetin and Fisetin to Kill Them

In addition to regular fasting, I do a protocol focused on killing senescent cells once a month, usually on the first Sunday of the month. Today’s 1/2/2022. So I’ll be both fasting and taking a large dose of fisetin and quercetin, two nutrients that have been found to kill senescent cells. I took 2,500 mg of each this morning along with a big glass of water. I’m hoping that the combination will kill off most of the problematic cells in my body.

Why Kill Senescent Cells?

Senescent cells are old, decrepit, half-alive cells which are no longer functioning properly. They’re sometimes referred to as “zombie cells.” They can’t divide anymore or carry on other normal cellular functions. What they can do is spread senescence to the adjoining cells.

According to the National Cancer Institute website,

“In biology, senescence is a process by which a cell ages and permanently stops dividing but does not die. Over time, large numbers of old (or senescent) cells can build up in tissues throughout the body. These cells remain active and can release harmful substances that may cause inflammation and damage to nearby healthy cells. Senescence may play a role in the development of cancer and other diseases.”

Pros and Cons of Senescent Cells

There are actually some benefits to having (some) senescent cells in our bodies (up to a point, in some circumstances). Here’s a quote from a study called “Fisetin is a senotherapeutic that extends health and lifespan” (with commentary):

  • “Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA.” So there can be an upside to senescence, in some situations.
  • But as the article goes on to say, “Senescent cells have been demonstrated to play a causal role in driving aging and age-related diseases using genetic and pharmacologic approaches.”
  • So there can be benefits to having some in the body, but also downsides. This makes it a judgement call. Many people in the anti-aging community are focused on getting rid of them, or at least cleaning out the body’s “stockpile” of zombie cells once in a while.
  • There’s no consensus on how often it’s good to ‘zap’ our senescent cells. Dr. Judith Campisi (a professor at the Buck Institute for Research on Aging and Adjunct Professor of Gerontology) who has studied them extensively, has speculated that it may (or may not) be good to get rid of them once a month, once a year, or once a decade.

How to Kill Them

If you do decide to get rid of them, how might you go about it?

Doing prolonged fasting is one way of getting rid of senescent cells.

When we fast, the body enters a state called autophagy. “Light” autophagy clears debris out of our cells’ nuclei; “deep” autophagy” starts breaking down our senescent cells to use as raw materials to make proteins to keep the body functioning in the absence of protein coming in through the diet.

Taking senolytics is another way of killing off cells that have gone senescent. Senolytics which appear to be effective include fisetin, quercetin, dasatinib and the antibiotic azithromycin. From an article called “Targeting senescent cell clearance: An approach to delay aging and age-associated disorders“:

“A further two proposed senolytic drugs with FDA approval are quercetin and dasatinib. One study revealed that dasatinib eliminated senescent human fat cell progenitors, while quercetin was effective against senescent human endothelial cells and mouse bone marrow-derived mesenchymal stem cells [27]. A combination of dasatinib and quercetin was effective in eliminating senescent mouse embryonic fibroblasts…

“Interestingly, clinical evidence supports the potency of azithromycin and roxithromycin in selectively targeting and eliminating senescent cells via the creation of anti-inflammatory effects.

“For example, azithromycin has been used in the treatment of cystic fibrosis and to protect the lungs from radiation damage [39]. Azithromycin exhibits anti-inflammatory effects by inhibiting the build-up of lung inflammation and fibrosis markers caused by radiation [40]. Roxithromycin shows more anti-inflammatory effects compared with those of azithromycin [41]….

So both drugs and nutritional supplements can help clear out senescent cells, as well as having other health benefits. But is it safe to take them for that purpose? Here’s another quote from the same study:

“Despite their apparent promise, however, researchers have shown negative effects of quercetin and dasatinib, such as pro-tumorigenic effects in mice [46] and causing the death of non-senescent human endothelial cells [47]….”

So Why Take Senolytics?

To be clear, I’m not recommending that anyone else get rid of their senescent cells; I’m just writing about what I’m doing. I attack mine once in a while, either through taking senolytics or through doing a prolonged (three to five day) water fast or fasting mimicking diet, because, broadly speaking, I believe that the benefits of clearing them from the body may outweigh the benefits of having them. And I’m also aware that old cells are always drifting in the direction of senescence. So if we clear out our zombie cells today, more will start accumulating in the body tomorrow.

If you decide to do something similar, I’d urge you to read up on both the possible side effects and possible benefits of the senolytics you’re taking. If you’d like to learn more about the pros and cons of getting rid of them, this recent talk by Dr. Campisi is a good update; I’d recommend watching both it and her other talks and interviews.

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2 Comments

  1. “Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA.” So there can be an upside to senescence, in some situations.

    This isn’t a pro in having senescent cells, it specifically is saying that it is good that cells enter senescence, and probably would be good if those cells get killed off so they don’t wake back up.

  2. Hi Jon, I’m taking senolytics to get rid of my senescent cells. I personally don’t want them into my body. But I think that, to get rid of them, it’s helpful to understand why the body allows them to accumulate. You might find this study interesting in that light:

    https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5643029/

    From the study:

    “Many cellular stresses activate senescence, a persistent hyporeplicative state characterized in part by expression of the p16INK4a cell cycle inhibitor. Senescent cell production occurs throughout life and plays beneficial roles in a variety of physiological and pathological processes including embryogenesis, wound healing, host immunity and tumor suppression. Meanwhile, the steady accumulation of senescent cells with age also has adverse consequences. These non-proliferating cells occupy key cellular niches and elaborate pro-inflammatory cytokines, contributing to aging-related diseases and morbidity. This model suggests that the abundance of senescent cells in vivo predicts ‘molecular’, as opposed to chronologic, age, and that senescent cell clearance may mitigate aging-associated pathology.”

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