Crowdfunding a longevity drug and Nrf2 activator
The first time I read about crowdfunding and citizen science in the context of longevity was on the pioneering imminst forums, now renamed to longecity. Back then we were brainstorming how to carry out longevity studies on pets at home, because who does not want their pet to live longer? Ever since then, I became convinced that these non-traditional funding approaches have some merit especially for medium-sized projects.
Currently, I am involved in helping Rapamycyn Longevity Lab and Ora Biomedical with work on their crowdfunded mTOR inhibitor screen, where as a first step we aim to find the most potent lifespan-extending mTOR inhibitors.
In another project that is closer to the clinic we want to demonstrate that sulforaphane can extend mouse lifespan. But why do we need money and how can you help?
Our goal is to show robust lifespan extension with sulforaphane
There is only one catch. Mouse lifespan studies are expensive. We managed to secure a deal that will allow us to run a study at below market rate. In fact, we are able to run a medium-sized lifespan study, with 70+ mice in the control arm and 70+ mice in the treated group, substantially cheaper than we dreamed was possible. We will utilize both male and female B6 mice.
Without going into technical and internal details of how to run mouse lifespan studies, Gpt-o1 estimates the cost of running a medium-sized mouse lifespan study of this type at 150 to 300k USD. Indeed, using contract research organizations (CROs) we could run the study on the lower end of this budget. This is still not affordable for us. However, we managed to get it at one-third of the lower end!
The only remaining problem is buying the drug which costs about the same or more than the whole mouse study. We can cover at least half of the cost but cannot in good faith pay more due to grant constraints. This is where your donation comes in: making cutting-edge research possible. An amount of 10k USD would help us to buy more of the drug for our experiments.
How to donate and donation goals
Ethereum/USDC wallet: 0xb410d23d478cFaf71DBEb9146C1D4fD04a8C0380
Bank account: 271-073783-0, DBS Singapore, Kamil Pabis
(please denote as “donation” or similar, drop me a message before making any large donations as these are perhaps better routed via the university)
Contact: kamilep123 on telegram, Aging_Scientist on twitter or via mail at Kamil.pabis@u.nus.edu
The donation goal is 10k USD.
Why test an Nrf2 activator like sulforaphane?
SFN activates Nrf2 which is one of the pro-longevity pathways with the most support. For example, Nrf2 signaling is elevated in the liver of long-lived mammals (Lewis et al. 2015) and underpins some of the benefits of CR (Pearson et al. 2008) and/or general cancer resistance in mice (Pomatto et al. 2020).
SFN is likely to show synergy with rapamycin since the latter is not a good Nrf2 activator in mammals (Tyshkovskiy et al. 2019)
SFN is attractive to pill-popping longevity optimizers and biohackers of the Bryan Johnson type. SFN is affordable, safe and available over the counter. You can take it now but without our study you will not know how likely it is to work in mammals.
SFN is important to aging biopharma. While you cannot make a lot of money with SFN for various reasons that I will not go into, mainly because it is an old natural compound with no good IP protection, it would nevertheless provide important validation of the Nrf2 pathway for longevity. Of course, there are also SFN-derivatives waiting to be discovered that might be more potent and more practical for biopharma.
Why test sulforaphane specifically and not another related drug or Nrf2 activator?
SFN is by far the best Nrf2 activator out there if you holistically evaluate the data for safety, preclinical efficacy, specificity and potency of Nrf2 activation. Some other related isothiocyanate compounds like PEITC also have good data. Many compounds are non-specific, weak Nrf2 activators muddling the literature with claims of Nrf2 this and Nrf2 that. Many of the same compounds are toxic, ineffective and impotent at realistic in vivo doses. SFN is one of the few compounds that has a 30 year history of successful preclinical data and that has demonstrated bona fide Nrf2 activation in human liver.
The main issues that have held back SFN are its instability and the high cost of pure SFN. We have a pretty good solution for the stability issue.
We decided to go with pure, synthetic sulforaphane in this project, because it has the best data. Undertaking a lifespan study itself is very risky and while we have considered using cheaper alternatives to SFN this would be an additional risk.
Our study is aimed as a direct replication of the below paper, just running it much longer, in both sexes and with larger sample sizes. We will use the same drug and same supplier (Bose et al. 2020)
Allocation of funding
lifespan mouse study, if there should be excess funding then the money will be used as noted below:
a follow-up mouse study focused on sulforaphane combinations or deep phenotyping of aged mice treated with the compound
vertebrate research in fish (lifespan study)
should there be an excess of funding it will be donated to the mTOR screening by Rapamycin Longevity Lab
Benefits to donors
one step towards curing and reversing aging
be the first to receive internal updates from the project (may require an NDA)
get the opportunity to co-author the final draft and have an input regarding experimental choices - real citizen science
References
Lewis, Kaitlyn N., et al. "Regulation of Nrf2 signaling and longevity in naturally long-lived rodents." Proceedings of the National Academy of Sciences 112.12 (2015): 3722-3727.
Tyshkovskiy, Alexander, et al. "Identification and application of gene expression signatures associated with lifespan extension." Cell metabolism 30.3 (2019): 573-593.
Pearson, Kevin J., et al. "Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction." Proceedings of the National Academy of Sciences 105.7 (2008): 2325-2330.
Pomatto, Laura CD, et al. "Deletion of Nrf2 shortens lifespan in C57BL6/J male mice but does not alter the health and survival benefits of caloric restriction." Free Radical Biology and Medicine 152 (2020): 650-658.
Bose, Chhanda, et al. "Sulforaphane prevents age‐associated cardiac and muscular dysfunction through Nrf2 signaling." Aging Cell 19.11 (2020): e13261.