Thread by @MartinBJensen

Livetweets from the 7th Annual Aging Research and Drug Discovery conference #ARDD2020. I can't attend every talk to coverage will be intermittent. Apologies to any speakers left out!

Christian Riedel from @karolinskainst presenting aging clocks. There are a lot of these, but excited to see him (A) making a human clock predicting time to death, not just age, and (B) deconvoluting both their human and model org clocks into FUNCTIONAL parameters. Sorely needed.

Now haut.ai from Estonia arguing that hand photos are more robust than faces for AI-based aging biomarkers, and that we need more explicit skin tone features for broadly applicable tools.
PS, Estonia is probably the world leader in digital health/EHRs.

@aubreydegrey from @agexthera commenting on @UnityBiotech's recent OA clinical trial results: "Clinical trials are experiments, and they often fail. That's normal, not a reason to lose hope in aging therapeutics".
And on #COVID19: Anti-aging for a less vulnerable population.

Gordian coming up after a short break! (No company twitter account, yet).

Polina Mamoshima talking about issues with AI-based aging clocks from blood samples: Specific contributing features don't map uniquely to biological aging, and clocks have large errors when applied to different genetic backgrounds than they're trained on. And yet there's signal.

Steve Horvath talking about a targeted array for scalable #Epigenetic clock measurements in mice. Disease models show accelerated aging (Huntington only weakly), CR or growth hormone KO slowed aging. Rapamycin only weak effect.

He has also made clocks that are compatible with human+elephant, human+cat, human+dog pairs😲

@ScheibyeKnudsen presenting a (secret) drug reducing #Senescence, determined by computer vision tracking cell culture senescence and drosophila movement with age. Supposed to boost #DNArepair, although I missed if he presented data for this.

back in my PhD days the mantra was that boosting DNA repair hadn't been successful for boosting lifespan, because toxic intermediates (e.g. strand breaks) mean that you'd have to boost the whole pathway while also keeping it in perfect equilibrium. Curious how this new drug works

Peter de Keizer arguing that 'senescence' is not a single phenotype across cell types😲. And some common senescence markers don't work at the single-cell level. He's making different cells from same iPS and inducing senescence, to determine cell type specific features.❤️

Why is he crushing our reductionist dreams, disrupting thehappy coexistence when we pretend that all #Senescence is the same?! Obviously because his company clearabiotech.com needs to figure out which diseases it can cure by targeting different senescence cells.

Debra Toiber from Ben Gurion U studying Sirt6 in DNA damage response: Independently recruited to DSBs within 5s, and recruits canonical HR & NHEJ proteins. Sirt6KO -> increase in p-tau, resembles tau174acetylation phenotype, increases nucleolus size/translation. Very interesting!

The excellent Tom Rando rounds out the day, talking about cycling D1 as an exercise-induced regeneration factor, seemingly transferable through #parabiosis. Paper: nature.com/articles/s4225…

@pak_heidi from @LammingLab did a great study decoupling #CaloricRestriction and #Fasting. For the uninitiated, CR in lab animals is normally achieved by once-daily feeding of a fixed amount, for practical reasons. The animals will eat all the food immediately and de facto fast.

Heidi used diluted and enriched food to achieve CR without fasting, and found that metabolic shifts in liver and muscle, and life extension, only occurred with a fast period! @KarlPfleger we've discussed whether fasting is as good as CR, but maybe it's the other way around :)

Rafa de Cabo presented pretty dramatic data on using disulfiram (commonly used to treat alcoholism by making you throw up when you drink) to increase autophagy and counteract the effects of high-fat diets.

The divide between bodybuilders and aging biologists widens, with @LammingLab data from old, young, & accel. aging mice: variable but mostly better health when limiting branched-chain amino acids in isocaloric diets.

(PS not implying Dudley Lamming is not a bodybuilder😇)

Between this, the recent @BuckInstitute paper on alpha-ketoglutarate (cell.com/cell-metabolis…), mouse to human translation and everything else, I think it's safe to say that macronutrients diets and longevity is still up in the air.

Alice Kane from @davidasinclair lab presented a random forest-based tool to score mouse frailty and est. time to death, based on a frailty index mirroring human clinical frailty: frailtyclocks.sinclairlab.org. Looks like a cool effort to help standardize aging mouse data.

Finally, @davidasinclair talks about my favorite #Aging topic: epigenetic loss of identity. Mostly this opus preprint: biorxiv.org/content/10.110…, where they used AAV to deliver OSK (no M) to old mouse eyes. RGC cells that receive cargo are protected from nerve crush/glaucoma model

New data: They see a reset of DNA methylation aging clocks with treatment. Adding shRNAs against Tet1 or 2 they lose the signal. Changing methylation sites were enriched for PRC2 targets. Repeating work in cerebral neurons.

Thanks for organizing this conference @ScheibyeKnudsen and @biogerontology! #ARDD2020

Side note: It was cool to see the new @NatureAging in the audience, and hear a new aging-focused @FrontiersIn
journal announced. More #Aging journals will be a great outlet both for studies of the fundamental biology, and (I hope) for linking basic biology to #AgeRelatedDisease.