The Cellular Senescence Network (SenNet) Program

Larger institutions such as the NIH are now beginning to invest a great deal more into fundamental research connected to cellular senescence. Twenty years ago it was clear enough that senescent cells were important in aging for the Strategies for Engineered Negligible Senescence (SENS) pioneers to include it in their initial scientific paper, but the topic was largely ignored by the mainstream of aging research. It took a decade to get to the point of a compelling animal study of targeted senescent cell clearance that convinced the rest of the research community. Five years after that the first senolytic-focused biotech companies were established, working on therapies to selectively destroy senescent cells. A further five years after that we come to this present moment, at which large institutional funding programs get underway to expand the basic science.

Early senolytic therapies are impressive in terms of the results they produce in mice: rapid rejuvenation, extension of life span, reversal of many age-related conditions. These approaches appear to top out at removing about half of the burden of senescent cells in some of the aged tissues assessed. There is definitely room for improvement. The primary concern in the scientific community is not efficacy of therapies, however, but rather the question of how senescent cells might have meaningful differences from tissue to tissue, or by cause of senescence, or other factors. Additionally, are existing means of determining the burden of senescent cells in tissue actually measuring all senescent cells, and are they mistakenly identifying any populations of non-senescent cells that happen to employ some of the same biochemistry?

This work will likely have little influence over the course of the present senolytics industry, the fair number of startup biotechnology companies and established pharma entities attempting to bring the first rejuvenation therapies to the clinic. Some of those first generation senolytics look very promising, such as prodrug approaches to limiting chemotherapeutics to activate only in senescent cells. It will, however, inform the next generation of anti-senescence therapies, which we should expect to be somewhat more effective as as consequence.

NIH launches program to map a rare type of non-dividing cells implicated in human health and disease

The National Institutes of Health has launched a program to study a rare type of cells, called "senescent" cells, that play both positive and negative roles in biological processes. The NIH Common Fund's Cellular Senescence Network (SenNet) program will leverage recent advances in studying individual cells, or single-cell analysis, to comprehensively identify and characterize the differences in senescent cells across the body, across various states of human health, and across the lifespan. The rarity and diversity of these cells previously made them difficult to identify and study; therefore, a deeper understanding will help researchers develop therapies that encourage beneficial effects of senescent cells while suppressing their tissue-damaging effects.

NIH is funding $125 million to 16 grants over five years, pending available funds. NIH issued eight awards for the creation of SenNet Tissue Mapping Centers, seven awards for Technology Development and Application Projects, and one award for a Consortium Organization and Data Coordinating Center (CODCC). The Tissue Mapping Centers will identify biomarkers of senescent cells in humans and then construct high-resolution, detailed maps of cellular senescence across the lifespan and physiological states. The Technology Development and Application Projects will be critical in advancing promising tools, techniques, and methods for SenNet to study senescent cells. As the organizational hub, the CODCC will collect, store, and curate the Network's data, tools, and models. These projects will work together to create a publicly accessible and searchable Atlas of Cellular Senescence.

Cellular Senescence Network (SenNet)

One cell dividing into two is a hallmark of development in living beings. However, as we age the tissues in our body accumulate a small number of specialized cells that no longer divide. These cells are called senescent cells, and they play important roles in health and disease across the lifespan. Under certain circumstances, such as aging, senescent cells accumulate and release a collection of molecules that can cause damage to nearby tissue. Under other conditions, such as cancer or wound healing, senescent cells can protect health by preventing tumor growth or releasing molecules that promote the growth of new tissue. Biomedical researchers still have many unanswered questions about how, when, why, and where senescent cells form, but their rarity and diversity make them difficult to identify and characterize in the body. Despite this, senescence is an attractive target for new therapeutics, with some already in development. A deeper understanding of cellular senescence will help researchers to develop further therapies that encourage beneficial effects of senescent cells while suppressing their tissue-damaging effects.

The Common Fund's Cellular Senescence Network (SenNet) Program was established to comprehensively identify and characterize the differences in senescent cells across the body, across various states of human health, and across the lifespan. SenNet will provide publicly accessible atlases of senescent cells, the differences among them, and the molecules they secrete, using data collected from multiple human and model organism tissues. To identify and characterize these rare cells, SenNet will develop innovative tools and technologies that build upon previous advances in single cell analysis, such as those from the Common Fund's Human Biomolecular Atlas Program and Single Cell Analysis Program. Lastly, SenNet aims to unite cellular senescence researchers by developing common terms and classifications for senescent cells.


Sorry but senolytics have a very long way to go

Unity is flailing, down $900 million in market cap and down to its last 12 months of cash, all while spinning its wheels in Phase 1 with a ophthalmic indication that has so much competition, it will most likely never see the light of day

Campisi is another example of a great researcher who should have stayed in the lab, optimized things there first, instead of dumping this dog on investors...

Posted by: Greg Kellman at October 28th, 2021 2:42 PM

@Greg Kellman
This shows that medical translation is hard, even if you have smart people working on the problem. Burning so much cache wouldn't be a problem if they weren't the poster child of senolytic startups. There is this perverse valuation heuristic where any bad news among the competition lowers the whole sector, regardless if the causes apply widely or not.

We should be more patient, though. I remember there was promising research using embryonic (at that time nobody was calling them "stem cells") to help heal spinal cord injuries in rats. This was during my highschool years. Late 80s, early 90s. Well over 30 years have passed and we barely have non-experimental functional therapies using stem cells. Organ printing is stuck in almost the same stage as 2005. We still have no solution for the vasculature. No brain replacement nor enhancement for me anytime soon. Doh.

On the other hand, now there is a lot of research on senolytics and new startups pop up every day. In a way senolytics were a lucky draw. Nobody was expecting to have such strong effects. As I remember the thinking was that there are lingering dysfunctional cells which don't perform as good as the young ones, take place and pose cancer risk. However, the pro-inflammatory secretion is an easy target with potentially high benefits. This is a single cause, or rather a class causes, which cause disproportionately high damage. Sounds too easy and too good to be true. Probably it is but it is still the most promising and lowest hanging fruit.

Posted by: Cuberat at October 28th, 2021 4:11 PM


Yes - you make good points on bio-pharma risk in general

I am just pointing out that this fledgling industry has been promoting itself as "the next big thing" - not just for cool technology to impact aging, BUT also to "MAKE US ALL RICH!!"

It is all BS...

Look at AgeX now - the poster child of in-vivo reprogramming, down like 90+%, hardly any cash on hand, and most likely going out of business, even with Juvenesence owning / promoting them!!

Aubrey talked about this recently that all theses companies should not be public, or have gone public, but here we are with some of the legs falling off the stool...and few paying attention

Posted by: Greg Kellman at October 29th, 2021 10:05 AM

@ Cuberat - Isn't there a good reason for SASP? Namely to draw the immune system's attention to damaged cells that may need to be cleaned up before they go malignant?

@ Greg Kellman. I hear you man. I bought in around $6 or $7 a share. You think this eye thing is going to fail?

Posted by: Matt at October 29th, 2021 11:01 AM


I don't know about failing - it's way too early

But when you have some decent clinical results, and your stock craters like it did, you know "the street" is not too confident on it getting anywhere in the coming few years

It also has major competition in the space, already on the market, so the positioning as a "last resort" drug, is another major drawback

Posted by: Greg Kellman at October 29th, 2021 12:39 PM
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