Although only in mice so far, this looks at first sight a promising study IMHO. To add to the good expectations, the compound proposed to combat this proven systemically driven senescence process via extracellular vesicles (EVs) is the easily available fenofibrate, commonly used to lower bad cholesterol (LDL-C) and increase good cholesterol (HDL-C) in people with high cholesterol or mixed dyslipidemia (elevated cholesterol and triglycerides).
Abstract
The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan.
Given the oustanding discovery and results in mice, it would be expectable human trials to be scheduled sooner than later. Crossing fingers here.
BTW this study adds to the theory - with Josh Mitteldorf as one notable spearhead - of a programmed and/or centralized aging process, with one or various sources of proaging factors. At the same time, it shows convergence with Dr. Harold Katcher’s E5 compound ongoing project who recently acknowledged was mainly based on rejuvenating extracellular vesicles (EVs). So it seems to be that when we start to get older our blood starts to become a sort of soup with growing in number pro-aging messagers, the ones subject of this post, and others blocking the diminishing rejuvenating and repairing juvenile factors. And to me Katcher’s E5 could be an attempt to counteract this and others EVs deleterious effects with their very same weapons.
Great catch, and an easy and safe intervention to try (fenofibrate) as many of us are already on statins for hypercholesterolemia. I wonder how it compares to D+Q?
Many senolytics are tissue specific and the D+Q protocol is one of those. It works on adipose and endothelial tissues but not many other tissue types. Fortunately we have a lot of adipose and endothelial tissue in our body that can respond to this protocol.
BUT this new study appears, on the surface, that fenofibrate is not acting specifically as a senolytic but a senescence inhibitor. Which in this case appears to be beneficial as we age.
Now I’ve got to order some fenofibrate
In the meantime I’ll be starting a cycle of the only known “systemic” senolytic FOXO4-DRI next week.
Even though I’ve been using my own little Q+F+OS (other stuff) formula for the past 4 years, cycling it every 3 months. I’m still kind of excited to give FOXO4-DRI a go.
Will you be taking bloodwork and measure other biomarkers before & after your FOXO4-DRI cycle? It would be very interesting to hear about that. Where did you obtain it, if you don’t mind me asking, and is it tested by a 3rd party lab? Good luck with your FOXO4-DRI cycle!
Until there is a definitive test for SASP burden, it will be difficult to clearly define the result. Yes hsCRP and SA-β-gal and a few others could be used to understand a bit but they are also not clear indicators of SASP as other things can influence those tests. Tissue biopsy is the way to go but I’m not doing that as cost and timing is not in my favour.
What I’m most interested in is to see physical results, not just measure them. Will my hairline improve? will my skin improve, will my tinnitus improve? just a few little age related things I’d like to see improve.
My annual blood work is currently the best it’s been in 15 years, not sure that would improve much but we will see in January when I get my annual checkup. I’m goping to ask for a Testosterone test, that is not typically part of the annual test but I’d be interested to see where that one lands.
I have relied on DNAm testing with Trudiagnostic. Have done 5 tests over 4 years so we have set of trends with that test. We (my wife Joan) and I in the Rejuvenation Olympics and both of us rank fairly well for our age Her latest PACE result is 0.76 and mine is 0.84
As far as where for FOXO4-DRI? I have my sources and yes fully tested but not 3’rd party as I trust my source and have done business with them for 4 years in other areas.
I am curious about why fibrates fell out of favor? I have seen where Tom Dayspring has written some favorable things about fibrates, but I have also read that fibrates combined with statins may be dangerous for some people. At first glance, fibrates seem to be effective low cost drugs.
@Steve_Combi found a source too (very pricey). But the research looks excellent! Going to aim to do the same asap. Please keep me in the loop about your experience
Jinfiniti offers a panel that measures β-gal, L-1β, IL-6, IL-8, TNF-α, and intracellular NAD: AgingSOS® Senescence & NAD Panel. It’s not cheap ($598 per test), but it would capture a lot of relevant data points. Though, really, you’d need to buy two tests for a before and after.
