#1

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.

Open Access Paper:

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#2

Effects seems quite large

Too bad the Medellian Ransomizadion paper on Rapa and longevity from 2023 pre-print has not been published or even updatedā€¦ anyone know anything more about that?

Or the marmoset paper?

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#3

I checked with Adam Salmon a few months ago on the marmoset paperā€¦ they are still working on it.

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#4

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 ā€œtomorrow or day afterā€ā€¦ that was weeks ago - now when asked, he says ā€œweā€™re still working on itā€. One rule - itā€™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, ā€œdonā€™t tell me when you think itā€™ll come out, instead tell me after itā€™s already been published, otherwise talk to the handā€.

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#5

What have you learned from the Bay Longevity Fair that could be shared here and or something you may consider to experiment?

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#6

See my comments and photos in this thread: Vitalist Bay, a Pop-Up City in the SF Bay Area

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#7

Anything specific that you picked up and are interested in trying?

Also, what is the consensus about rapamycin at the fair?

#8

Also interesting: SLC16A6 codes for a taurine-selective membrane transporter.

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#9

No - nothing new that we donā€™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 Conboyā€™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. Itā€™s generally a more knowledgeable longevity crowd attending from what I could tell from talking with people.

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