In this study, we investigated the contribution of rare coding variants to human longevity by analyzing whole exome sequencing data from 1245 German long-lived individuals (LLI) and 4105 geographically matched younger controls. We identified novel exome-wide significant associations at both the single-variant and gene level, with a significant over-representation of genes involved in mechanistic target of rapamycin (mTOR) signaling. As such, three rare single variants in the mTOR-pathway genes RPS6, FLCN, and SIK3 were enriched in LLI. Additionally, RWDD1 emerged as a strong candidate gene for longevity, with LLI exhibiting a statistically significant burden of rare missense variants in this gene. Other associations involved PRAC2, SLC16 A6, FOCAD, IHH, MESD, HOXA4, and DNAJB13. Furthermore, we observed an enrichment of protein-truncating variants in the genes ASXL1 and TET2 amongst LLI, likely as a result of clonal haematopoiesis. The study emphasizes the role of rare variants in human longevity, particularly through mTOR signaling.
German longevity study reveals novel rare pro-longevity alleles clustering in mTOR signaling pathway
Effects seems quite large
Too bad the Medellian Ransomizadion paper on Rapa and longevity from 2023 pre-print has not been published or even updated… anyone know anything more about that?
Or the marmoset paper?
I checked with Adam Salmon a few months ago on the marmoset paper… they are still working on it.
Even the people involved are bad at estimating when a study will come out. For example Dr. Brad Stanfield said his rapamycin study would come out “tomorrow or day after”… that was weeks ago - now when asked, he says “we’re still working on it”. One rule - it’s always later than any date given. There are studies out there that were concluded literally years ago, that I keep checking for updates, and crickets. Some may never come out, if serious problems are uncovered. My attitude to all these is, “don’t tell me when you think it’ll come out, instead tell me after it’s already been published, otherwise talk to the hand”.
What have you learned from the Bay Longevity Fair that could be shared here and or something you may consider to experiment?
Anything specific that you picked up and are interested in trying?
Also, what is the consensus about rapamycin at the fair?
Also interesting: SLC16A6 codes for a taurine-selective membrane transporter.
No - nothing new that we don’t know about and already cover here. Most of it is more forward-looking, discussions about things that are still in the research phase (like Irina Conboy’s new treatment to reduce the harmful factors in blood, that is going into some clinical trials).
Lots of interest and use of rapamycin by participants at the Vitalist conference. It’s generally a more knowledgeable longevity crowd attending from what I could tell from talking with people.