New insights on cellular clones and inflammation in bones

Medical Xpress / University of Pennsylvania / Cell ^ | June 5, 2024 | Nathi Magubane / Hui Wang et al

[ConservativeMind]

As humans age, hematopoietic stem cells—the immature precursor cells that give rise to all blood and immune cells—accumulate mutations. Some of the mutations allow these stem cells to self-renew and expand more effectively than their non-mutated counterparts.

This relatively poorly understood condition, known as clonal hematopoiesis of indeterminate potential (CHIP), is detectable in more than 10% of people older than 65 and is linked to increased risks of various inflammation-related diseases.

"These mutations change the character of the progeny cells, making them more inflammatory," says George Hajishengallis. "When a large fraction of your immune cells are derived from these mutant stem cells, it spells bad news for chronic inflammatory diseases."

Now, a team uncovered mechanistic insights into CHIP. They also found an FDA-approved drug for preventing organ transplant rejection, rapamycin, has the potential to block these mutant stem cells and treat CHIP-driven inflammatory bone loss diseases, such as periodontitis and arthritis.

"We found a compelling observational association between DNMT3A, a gene affected in CHIP, and the prevalence and severity of periodontitis in a cohort of 4,946 people aged 52 to 74," Hajishengallis says.

The UNC researchers studied the association by analyzing genetic data and clinical characteristics of the 4,946 community-dwelling study participants.

The Hajishengallis lab's animal model had a mutation analogous to a common human DNMT3A mutation found in CHIP.

These mutations led to an increase in cells that break down bone tissue, higher levels of a protein involved in inflammation, and impaired function of regulatory T-cells, which normally keep the immune response in check.

The presence of the DNMT3A mutation resulted in overactive signaling of mTOR—which regulates cell growth, proliferation, and survival—in the hematopoietic stem and progenitor cells with CHIP mutations.

Hajishengallis says, "Screening for CHIP among the elderly population may identify individuals with increased risk for inflammatory comorbidities."

[ConservativeMind]

More than 10% of people over 65 have this issue, and they may naturally know they are at high risk, simply due to having chronic inflammatory diseases.

Fortunately, this can be tested and it appears rapamycin can help correct this runaway mutation. Rapamycin (Sirolimus) is currently available for prescribing. It is most often used for organ transplant recipients.

GoodRX shows it for around $32 a prescription at places like Target and CVS.

In recent years, it has been found to help get rid of dysfunctional cells.

[ConservativeMind]

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[icclearly]

.....it appears rapamycin can help correct this runaway mutation.

So, let me understand your comment. You are suggesting that we rush out and first find a doc to prescribe rapamycin and spend $32 for the miracle drug.

Where is the double-blind placebo-controlled human study that supports your directive?

Why not talk about the effects of exercise and fasting that may have the same or even better effect? And, you don't need a script or a pill for $32. That is if your goal is to improve health and longevity.

Snake oil.

[ConservativeMind]

It's not snake oil. I've posted multiple other studies around such senolytics, some with human trials.

This is just an additional area of coverage that may also help explain positive outcomes in prior studies using rapamycin.

[Pelham]

Rapamycin sounds somewhat similar to Rituximab but vastly less expensive. There might be some overlap in treating autoimmune disorders.

[Tilted Irish Kilt]

(From the article) : " As humans age, hematopoietic stem cells—the immature precursor cells that give rise to all blood and immune cells—accumulate mutations.
Some of the mutations allow these stem cells to self-renew and expand more effectively than their non-mutated counterparts."

This might also explain why many elites on the West Coast have encouraged many older adults and politicians to obtain blood transfusions from younger, and known, donors.
While it may seem ghoulish to many, such transfusions would offset the aging process and replace and help get rid of old dysfunctional cells and the immune cells—accumulate mutations.