Five compounds extended lifespan in old mice
Five of ten selected compounds extended lifespan in old mice, but a less successful second series leaves the reliability of selection by gene activity uncertain.
Five of ten compounds extended lifespan in old mice
A preprint by Anastasia Shindyapina and Alexander Tyshkovskiy from Harvard professor Vadim Gladyshev’s group reports this result. The work is still under peer review. Eternal Search has a page for Alexander Tyshkovskiy.
The researchers selected compounds using patterns of gene activity associated with longevity. They started with Connectivity Map, a database recording how more than 4,000 compounds change gene activity in cells. They then tested candidates in human liver cells and gave 25 compounds to young male mice for a month, measuring gene activity in the liver and kidneys.
Nine compounds were selected using a combined score across three tests. The tenth, KU0063794, had been identified through the same approach and tested in mice in 2023. All ten were given to mice aged 24 to 25 months. Four inhibitors of proteins that regulate cell growth (KU0063794, AZD8055, LY294002 and selumetinib) and the natural anti-inflammatory compound celastrol extended lifespan. For LY294002 and AZD8055, the effect appeared only in males.
The five out of ten result applies to one selected set of compounds. In a second series of experiments with other compounds, the authors are so far finding substantially fewer successes. It is therefore too early to expect this selection method to produce a successful candidate half the time.
Assessing the method’s reliability requires testing how often the compounds it selects extend lifespan in subsequent experiments. Those tests will show how useful gene activity changes are for selecting candidates before costly lifespan experiments.
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Sources
[1] youtube.com
[2] doi.org
[3] pubmed.ncbi.nlm.nih.gov
[4] nature.com
[5] pubmed.ncbi.nlm.nih.gov
[6] t.me
This item was selected because it links a concrete mouse lifespan result to Alexander Tyshkovskiy, a named preprint author with a public Eternal Search page, while giving readers the evidence needed to judge why five successes do not yet establish a reliable screening rate.