As we age, we accumulate more and more cells that have stopped dividing and have stopped functioning normally,
but are still metabolically active and are having an adverse effect on the surrounding cell,
and these cells are called senescent cells.
Today, we’re going to take a look at senescent cells and we’re also going to take a look at senolytics,
the drugs that have been developed to clear them out.
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One of the most exciting areas of the research into longevity is the studies being done on cellular senescence.
In today’s video, I’ll be explaining exactly what a senescent cell is,
how it becomes senescent, and the impact that cellular senescence can have on aging.
We’ll also take a look at some of the drugs and supplements that have been developed to
help clear senescent cells from the body.
OK, we all know that cells divide. If you think back to high school biology,
the cell cycle starts with a process called mitosis,
which is where replicated chromosomes are separated into two new nuclei
…with each of the daughter cells being genetically identical to the parent cell.
In the early 1960’s, two researchers named Leonard Hayflick and
Paul Moorhead discovered that after about 50 divisions, normal cells will cease to divide,
and this is called the Hayflick Limit.
On the end of every chromosome is a segment that contain no genetic information,
and this “end cap” is called a telomere. Each time the cell divides and the chromosome is replicated,
a little material is lost from the end of the telomere.
They erode thoughout the life of the cell, until, after they reach the Hayflick Limit of about 50 divisions,
they almost disappear to leave the DNA information bare.
DNA is no longer protected by the telomeres when it replicates,
and critical information gets “chewed out”.
Think of them like the plastic caps at the end of shoelaces.
Without the caps, shoelaces become frayed, until they can no longer do their job.
Same with telemeres…and as they become frayed, they expose the DNA to damage.
And to make matters worse, cellular division isn’t the only thing that will shorten telomeres…
they can also be shortened by stress, smoking, obesity, lack of exercise and poor nutrition.
Once the damage to the DNA becomes severe enough, most cells stop functioning normally,
they stop dividing and they enter apoptosis, which is the programed death of the cell.
But some cells stop functioning normally and then, instead of dying, they become senescent.
Although the senescent cells can no longer replicate, they remain metabolically active
and typically provoke an immune response through the secretion of pro-inflammatory factors,
including a bunch of substances with names like: cytokines, chemokines,
and extracellular matrix proteases.
And these substances form something called the “senescence-associated secretory phenotype”, or SASP.
Although senescent cells make up a really small percentage
of all the cells in the body, the effects of the SASP can be profound.
SASPs can adversely impact the surrounding tissue microenvironment,
interfering with the normal functioning of such process as tissue regeneration and remodeling,
inflammation and the formation of cancerous tumors.
Not good. And as we grow older, we accumulate larger and larger numbers of senescent cells,
and this accumulation of senescent cells is thought to be a major contributing factor to the aging process.
This research into cellular senescence is one of the more interesting areas of longevity research.
At least, that’s what I think. If you agree and you’d like me to do more videos on this subject,
leave me a comment below and let me know what you think.
So, what can you do about the accumulation of senescent cells in your body?
Researchers have been studying a class of molecules called senolytics,
which can selectively induce death in senescent cells and remove the SASP.
They found that senescent cells have an increased expression of pro-survival genes
which make them resistant to apoptosis.
Now, there are some drugs that target these pro-survival factors,
and by nudging the senescent cells towards apoptosis,
they can selectively kill senescent cells, without having any impact on normal cells.
There are 2 of these drugs that I’ve heard of; one is called dasatinib,
and it’s used in the treatment of some forms of leukemia.
The other is called quercetin,
and it’s a flavonoid antioxidant and plant pigment found in deeply colored plants.
Both were able to remove senescent cells but were more effective in different tissues.
Dasatinib was found to be effective in destroying senescent fat cell progenitors,
which are biological cells that are similar to stem cells, but are more prone to differentiate into a specific target cell.
And quercetin was found to be effective against human endothelial cells.
However, it was discovered that combining the two drugs formed a synergy
that was significantly more effective at removing some types of senescent cells.
It was also discovered that a removal of as little as 30% of senescent cells was enough to slow down aging.
And not all senescent cells are harmful.
They play a significant role in cellular reprogramming and wound healing.
So it’s a question of balance:
too few senescent cells can be just as bad as too many,
and the role of senolytics is to clear just enough senescent cells
to slow aging without impinging on cellular reprogramming or wound healing.
Now, Dasatinib requires a prescription, since it’s used to treat leukemia, and it’s VERY expensive.
Quercetin, on the other hand, can be easily purchased as a supplement
and can be found naturally in many foods, including red wine, green tea, kale, blueberries, cranberries & dark chocolate.
Quercetin is also an anti-inflammatory, a natural antihistamine,
helps protect the skin and promotes a healthy liver.
A lot of the study into senolytics has happened under the umbrella of cancer research.
A number of possible senolytic agents are being studied for their ability to target cancer prevention pathways.
One is Navitoclax, an experimental anti-cancer drug and senolytic agent.
It can induce apoptosis in senescent cells, but not in non-senescent cells,
and it has a protective effect against memory loss in mice genetically engineered to simulate Alzheimer’s.
So while quercetin may be the only senelytic drug that can be easily obtained currently,
that I know of, I think there’s going to be a lot more, and a lot more powerful,
senolytics available in the not-to-distant future.
The adverse outcomes that senescent cells can have on the body can be way out of proportion to their population,
exhibiting a really harmful effect on the surrounding tissue microenvironment.
And as we’ve seen, they can start accumulating in the body as we get older,
until they eventually become so abundant that their effects overwhelm the normal functioning of cells…
and we start to age. But researchers have developed a number of senolytic agents
that have the ability to clear the senescent cells from our body.
Now, while a lot of these are prescription or experimental drugs
that can be difficult or impossible to obtain,
the supplement quercetinhas been shown to be a senolytic agent.
It’s widely available, and easily affordable.
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