Cellular senescence is a major contributor to age-related diseases in humans; however, it also has a beneficial role in physiological and pathological processes, including wound healing, host immunity, and tumour suppression. Reducing the burden of cell senescence in animal models of cardiometabolic disorders, inflammatory conditions, neurodegenerative diseases, and cancer using pharmaceutical approaches that selectively target senescent cells (ie, senolytics) or that suppress senescence-associated secretory phenotype (ie, senomorphics) holds great promise for the management of chronic age-associated conditions. Although studies have provided evidence that senolytics or senomorphics are effective at decreasing the number of senescent cells in humans, the short-term and long-term side-effects of these therapies are largely unknown. In this Review, we systematically discuss the senolytics and senomorphics that have been investigated in clinical trials or have been used off-label, presenting their various adverse effects. Despite the potential of senotherapeutics to transform anti-ageing medicine, a cautionary approach regarding unwanted dose-dependent side-effects should be adopted.
Wow! Fantastic paper. Now I just need the time to do a deep dive.
I wonder if age factors into the calculation. Perhaps someone in their 40’s should get rid of the senescent cells, but someone in their 80’s shouldn’t.
Good episode about senescence from the new and excellent Buck Institute podcast
Interesting point. I was thinking the opposite, but my logic may well be skewed.
If you’re younger then a senescence inhibiting drug, like rapamycin, would allow your reasonably efficient system to naturally clear any senescent cells that needed clearing.
Whereas someone starting rapa later might benefit from some clearing out through senolytics because your immune system wouldn’t be up to the job.
Is there a rapa + senolytic study in mice that looks at age of intervention?
I don’t think Rapamycin kills senescent cells. I think it makes them function properly. (not all of them, but some of them).
I think you’re right that rapa doesn’t kill senescent cells but it does stop/slow the creation of new senescent cells.
The immune system naturally clears some senescent cells, and the younger you are the better job it does.
I have done a video about the experiment I have been running. At the moment it is unlisted, but I will link it below if anyone is interested.
I don’t really reference Rapamycin although I am taking it infrequently. I think what I am doing is compatible with Rapamycin in that the different approaches combine positively, but most of what I do does not relate to Rapamycin.
At this point, I have to believe that Rapamycin saving cells from senescence plays into it’s longevity factors. It truly is a wonder drug.
Anti-Aging Medicines Seek To Eliminate “Zombie” Cells – But Could This Be Dangerous?
According to a recent study from the University of California, San Francisco, not all senescent cells are detrimental “zombies” that need to be eliminated to avoid age-related diseases. Instead, some of them are embedded in young, healthy tissues and promote normal recovery from damage.
Scientists have now seen these cells in action in lung tissue as well as other organs that serve as barriers in the body, such as the small intestine, colon, and skin. When they employed drugs known as senolytics to eliminate these cells, lung tissue damage healed more slowly.
I think zombie cells should be made to work and function as part of the entity. In that sense they cease to be senescent.
Thanks Rap Admin for sharing this article/study. Really makes one think before taking meds to eliminate Senescent cells. As you know, I’ve been on the fence regarding this program and readings like these may keep me on the fence.
See article below, discussing senolytics and senomorphics. Article lists rapamycin, metformin, resveratrol, stains, even acarbose and 17 estradiol as senomorphics.
Another HMG-CoA reductase inhibitor simvastatin was also shown to decrease SASP expression in senescent human fibroblasts and suppress the cell non-autonomous cancer-promoting effect of SASPs in breast cancer cells.
Several naturally occurring flavonoids, particularly apigenin and kaempferol, were demonstrated to significantly inhibit SASP production in bleomycin-induced senescent BJ fibroblasts.
Likewise, lifespan extension and other beneficial health effects of acarbose and 17-α-oestradiol have been reported, but whether it is related to its senomorphic activity remains unclear [[183]]. Two Ca2+ channel blockers, loperamide and niguldipine, and dopamine antagonist fluspirilene also displayed a senomorphic effect on primary MEFs; however, only a single concentration was tested
Targeting cellular senescence with senotherapeutics: senolytics and senomorphics
John_Hemming, your video doesn’t explain what you did. Will you share your protocol?
Procyanidin C1 is also a senomorphic at low doses. Since the amount of Procyanidin C1 in grape seed extract is unknown (mixed cyanidins), GSE may function as a senomorphic.
PCC1 blocks the SASP expression when used at low concentrations. Importantly, it selectively kills senescent cells upon application at higher concentrations, mainly by enhancing production of reactive oxygen species (ROS) and disturbing mitochondrial membrane potential, processes accompanied by upregulation of Bcl-2 family pro-apoptotic factors Puma and Noxa in senescent cells.
Procyanidin C1 is in grape seed extract (GSE)
FWIW I take pterostilben{1,000mg]and GSE{800mg] together, every day.
pterostilben 250mg, 4 capsules {1,000mg total]
GSE 400mg, 2 capsules {800mg total]
Thanks for this Juan. I googled for procyanidin C1 and discovered my Aronia berries have it as well. Also in the same article it says they have alpha glucosidase inhibitor:
It says they have it in the bark too and since we had to mow them all down this fall I have a mountain of bark down there. Haven’t seen any recipes on how to harvest that though.
I put a couple cups of frozen berries in my morning smoothie maybe twice a week. Also have 2 daughters that eat them, but they are a hard sell. People are interested until they try them.
Pycnogenol (pine bark extract) has procyanidin C1 too.
You have to mow the bushes every 6 years or so. For one thing they get too big for the picking machine, but also the yield gets worse over time:
This is just one pile. So if anybody wants to try aronia bark it can be had very cheap here.
This is what they look like after being mowed off.
I can see why they are grown. There are many positive attributes here and they’re relatively cheap.
Thanks for the tip. I ordered Aronia powder months ago, after some research (not related to senomorphics). on cyanidins. I put them in coffee. I have to find it somewhere among my supplements and start again.