Olde Scooter's Favorite Theory of Aging

(Theory Belief/Hope about) Aging Itself

The Geroscience Hypothesis

  • Duff, another of your rants on senolytics?

    In a nutshell:  Aging is caused by many things, but the buildup of senescent cells as we age is one that is both a CAUSE and and EFFECT of aging. Circular, no?  As time goes by, compounding damage happens to cells that causes them to become senescent -- no more dividing and replicating but they don't die, they just hang around and emit SASP* which has inflammatory and other nasty molecules that speed up that long slide to death by "natural causes."** 
  • Old people build up a LOT of senescent cells. They weaken the immune system that clears them out in younger people, more circular deterioration.
  • GETTING RID OF SENESCENT CELLS WILL POSTPONE THAT. 

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As I read more about it, I started blasting out blog posts in late 2017. I was smitten by this paragraph:

“Aging is the main risk factor for many chronic degenerative diseases and cancer. Increased senescent cell burden in various tissues is a major contributor to aging and age-related diseases. Recently, a new class of drugs termed senolytics were demonstrated to extend healthspan, reducing frailty and improving stem cell function in multiple murine (mouse) models of aging.”

Even further back, the earliest (perhaps) research came to this conclusion in 2011:

A significant discovery

In 2011, scientists from the Kogod Center on Aging (part of Mayo) published research that was named a "Top 10" discovery by the journal Science. The findings, which were published in the journal Nature, proved the role of senescent cells in the aging process. 

"Proved!" I like definitive statements. Billion$ are going toward finding and testing existing and newly developed senolytics. (Well, maybe not billions -- yet.)





Specific Diseases and Senescence

Much of the research so far has been to learn if Senolytic drugs are effective on specific age-related diseases. (Probably because the FDA doesn't classify aging as a disease, so researchers go after specific end-gamers that can be patented and sold for big bucks.)

IPF   Idiopathic Pulmonary Fibrosis-- always fatal

One of the first pieces I read on senolytics was about a Mayo Clinic study way back in 2019 on a small sample of people with fibrotic lung disease (IPF), which is accompanied by a lot of senescent cells. Here is a layperson readable summary.     The full research paper (for you megabrains out there) is linked in footnote 2. It's promising.

Neurological Diseases
"Combination of dasatinib and quercetin (senolytics) improves cognitive abilities in aged male Wistar rats, alleviates inflammation and changes hippocampal synaptic plasticity and histone H3 methylation profile."  OK, just rats so far, but many studies are underway. Watch this space.


Eye Diseases
Possibly the first senolytic medication to get FDA approval and come to market is a concoction called UBX1967.  It is aimed at macular degeneration and has completed Phase 2 clinical trials evaluating its safety and ability to clear senescent cells in patients with AMD. The pharma company is Unity Biotechnology. FDA approval might come next year.
   


OK, Now let's Get Personal... How about age-related prostate problems?

Definitely personal, right up my alley, so to speak. This is another ailment  -- surprise! -- that comes with aging.  More than half of us 85+ guys have BPH, enlarged prostates. Makes some men's take-a-leaker almost leakproof. 

  • Some studies propose that senescent cells may play a role in the development of BPH:
    • Cellular Senescence in Prostate Tissue: Researchers have identified senescent cells in the prostate tissue of men with BPH. These cells exhibit markers of senescence, such as increased expression of p16INK4a and p21CIP1.
    • Inflammation and Senescence: Chronic inflammation is associated with BPH. Senescent cells release pro-inflammatory molecules (the senescence-associated secretory phenotype, SASP), which can contribute to inflammation and tissue remodeling

THAT'S ALL WELL AND GOOD, BUT...

The big idea is that senolytics will help the aging and aged with ANY ailment that is disadvantaged by too many senescent cells. Eyes, livers, spleens, noses, brains, skin, toes... the whole skinny dipper, will be better at fixing their ailments when they have fewer SCs.

I encourage you to go nuts Googling and Binging on this subject. Or ask one of the AIs about any of this stuff. I am convinced that this whole "senolytic" idea is going to be big big big news.

SELF EXPERIMENTATION (I advise against it, but I do it.)

I am now almost a year into using a self-prescribed senolytic cocktail of Quercetin and Fisetin, easily available over-the-counter supplements. Just last month I added another one, Piperlongumine.  I take one fairly heavy two day dose every two and a half weeks. Several of the dozens of research papers I have read recommend this. I believe (!) I feel positive results. I'll keep you posted.


*SASP = senescence-associated secretory phenotype!

**"Natural Causes" you read about in obituaries are those diseases that do us in most of the time, that are our terminal switches:   Heart, Stroke, Neurological (mostly Alzheimer's), Cancer and lung failure.  That's the Big Five -- plus many less common ailments that push us over that final cliff. Truth is, when we get decrepit some damn thing or another will finally pull the plug. These are called "age-related diseases" because the more we age, the more we get them.

1. More Fountain of Youth Stuff

2. Senotherapeutics

3. Dasatinib + Quercetin and diabetic kidney disease

4. "Greater impact than curing cancer."


Old man Pix credit:  MS CoPilot Designer


BONUS (a purely speculative aside)

My current senolytics fixation gives me a powerful self-induced placebo effect.  I believe that I am cleaning out my old man's surplus of senescent cells, thus releasing my self-healing capacities that have been gradually degraded by those senescent bastards. By so believing, whatever benefits I'm getting from the senolytics is augmented by this. 

I think there should be a new category of medicine called placebomics.Oh, t

.Oh wait!  There is!      :   

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