Poster Issues for: 74th Annual Scientific Meeting of the BSRA (2025): The Biology of Ageing - BSRA

[AustraliaLongevity]

@John_Hemming

I would not myself say “Doses were too low to change lifespan” as we don’t know they will change lifespan at a higher dose.

Fair point. We will see what happens. But I think it’s still a true statement, if lifespan didn’t meaningfully go up or down then the dose is too low. Everything will have an effect at some dosage level.

[John_Hemming]

Another infographic.

[John_Hemming]

I have updated the poster quite a bit. Here are two photos

[John_Hemming]

[John_Hemming]

Point mutations and the mutator mice
Vermulst et Al’s paper from 2006 which studied mutation quantification in the heterozygous and homozygous mutator mice warrants further comment. Although they did not study lifespan analysis this paper reported median lifespan estimates from previous papers (Trifunovic et al., 2004; Kujoth et al., 2005) where wildtype mice survived 864 days, homozygous mice survived 423 days and heterozygous mice survived 758 days. So there was an estimated 41% reduction in lifespan for homozygous and an estimated 12% reduction in lifespan for heterozygous. Although accurately reported in the paper that no statistically significant difference was detected (p=0.875) between heterozygous and wild type mice, the paper has been considered elsewhere as it concluded there was no difference rather than it did not find a difference. What was also found by Vermulst was that young heterozygous mice had a higher level of mutations than old wild type mice. From this it could be hypothesised that transitions (the main replication error) appear to have much less effect, perhaps an order of magnitude less, on the efficiency of the mitochondria than deletions and transversions (the main errors from ROS). They recognise in their paper that their methods would not detect large mtDNA deletions although they would detect small mtDNA deletions. Hence their paper does not conflict with the thesis that the mutations caused by the replication errors in DNA Polymerase Gamma cause a lifespan reduction in both the heterozygous and homozygous mutator mice compared to wild type, but this has a significantly less effect than mutations caused by ROS rather than replication errors. Importantly their paper does not conflict with the thesis that the main cause of aging is mitochondrial mutations caused by ROS rather than replication errors, but that replication errors do have a minor effect on aging.

[AustraliaLongevity]

Looking great John!

Another excellent thing that is worth including is the mTOR inhibitor/modulator screening project:

Crowdfunding Project Looks for a “Better Rapamycin”

Please help out in amplifying the social media posts so that we increase the chance of getting the project fully funded. https://x.com/KristerKauppi/status/1945062001274708269 The social media post This is the day I have been waiting for and it’s time to start to release preliminary data from the first phase of the lifespan screening of 301 of 601 compounds in roundworms. Below is the current top list of the 37 compounds. Out of the 301 compounds tested 5 have produced a higher median lifespan extension than than the best recorded lifespan of Rapamycin which is 27%. My three key takeaways from this is When I started to look deeper at the compounds in the top list I was surprised that there were 3 compounds that indirectly activated mTOR instead of inhibiting it. This unexpected result turned out to be fortunate because the goal was to screen 601 mTOR inhibitors and not look at mTOR activators. It’s still early data but this challenges the assumption that mTOR activators would …

Lots of amazing data has come out of this and work is being done using this data in big ways.

[John_Hemming]

I can add this to the web page. If someone gives me words to add.

[Krister_Kauppi]

@AustraliaLongevity Thanks for the highlight there! And impressive journey and nice work with the poster, @John_Hemming!

[Krister_Kauppi]

Thanks for the support, John! Here is a text of the mTOR modulator project. If you need a shorter version just let me know.

Searching for a better Rapamycin
Rapamycin is the gold standard for lifespan extension, but better options may exist. Rapamycin Longevity Lab has already screened 300 mTOR-modulating compounds. Five of these outperformed Rapamycin’s 27% lifespan effect, with Omipalisib achieving a remarkable 63% increase.

Additional 300 compounds are soon to be screened once we obtain the remaining $23,400 funds needed. The goal with this project is to provide the field with important unique data to improve human longevity.
Donate: https://masteronething.com/mtor

[John_Hemming]

I have put a section on the web site post after the text about Rapamycin

[John_Hemming]

I bought a month’s subscription for the mindthegraph infographic design system so I thought I might do some more before it runs out. I have finished the physical poster subject to changes from more results about IPAM, but I am updating the web page.

Here is another one.

[John_Hemming]

Another two

[John_Hemming]

This was a hard infographic to create. I think it is because the issue is so complicated as it involves an element of randomness as well as average changes.

[John_Hemming]

I thought people might like this

[John_Hemming]

Because it stimulates… mTOR

[John_Hemming]

Collagen is v low on leucine

[John_Hemming]

[John_Hemming]

[John_Hemming]

“prehabilitation” is interesting as a concept. Exercise the day before an operation, but not two days before reduces muscle loss from the operation.

[John_Hemming]