Abhishaike Mahajan

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Yeah Arcadia is definitely less on the blue-sky/high-variance realm of the spectrum, and closer to 'better research in underserved areas of biology'. 

I was pondering adding Altos Labs here, alongside Retro Bio and Newlimit, but they do feel a bit different from others here given the strong focus on a for-profit system (Arcadia's for-profit focus is a bit more opportunistic). 

Arc probably has discovered the most influential thing: https://arcinstitute.org/news/news/bridge

Arcadia Science has a grab bag of a bunch of interesting stuff: https://research.arcadiascience.com/ 

Everyone else is a bit too new to have released many interesting things

Great catch, dumb mistake on my part, fixed! 

As for the latter question, I looked into this, and I think the 2 day 'on' of YF expression is literally just the max time it can be expressed without deleterious effects. I think people haven't investigated the 'off' cycle time as much. I suspect people are on the 'the more reprogramming I can do, the better' train up until recently, so that level of optimization likely is higher handing fruit. 

From here: https://www.nature.com/articles/s41467-024-46020-5
"The currently optimized method of partial reprogramming is the maturation phase partial reprogramming, which necessitates 13 days of continuous expression of Yamanaka factors in vitro...However, this optimized in vitro method may be highly damaging in in vivo models, as a continuous expression of Yamanaka factors for more than 2 days may have lethal effects in mice8,67. In vivo studies now focus on cyclic partial reprogramming...."

Thank you for reading! 

Senescent-cell-based therapeutics feels like somewhat of a dead-end...senescence happens for a reason, and clearing out these cells have some second-order downsides. E.g., the inflammation caused by senescence is important for acute injury repair. I am less well-read on this area though!

Metformin and rapamicyn are promising in the same way ozempic is promising; helping curtail metabolic problems helps a LOT of things, but it won't lead to dramatic changes in lifespan. Definitely in healthspan! But even there, nothing insane. 

Imo, partial cellular reprogramming is the only real viable approach we have left, I'm kinda unsure what else the field has to offer if that ends up failing.