April and May events and news - VitaDAO, ARDD22, Singapore and more

This is my personal selection of events of interest to professional biogerontologists and those who are following the science of aging. Do let me know if there are any additions to be made.

  • Grants
  • Impetus grant round 2 application will open at the beginning of May and close at the end of May. This time around it is not an open application as in round 1, but a call for specific projects that align with topics such as interventional human studies involving omics endpoints or validation of methylation clocks (direly needed). Go check it out.
  • Upcoming events
  • updates for the below events will be posted on the VitaDAO webpage.
  • 28th of April - The Science of Biostasis and Cryopreservation.
    Dr. Emil Kendziorra, Founder & CEO at Tomorrow Biostasis and Kai Micah Mills, Founder & CEO Cryopets
  • 12th Of May - Technologies for Longevity Medicine.
    Will be Cohosted with ARK from Kings College - speakers TBD
  • Recorded events and seminars
  • The first VitaDAO crypto longevity symposium was held online on the 13th of April and is available on youtube for those who have missed it. The advent of online-only and hybrid conferences that are being streamed and uploaded to youtube is one of the big changes heralded by the pandemic. It seems like we have lost the battle against the virus, but won the war. Life is slowly returning to normal, with minor improvements.
  • Regular online events, talks, podcasts and webinars
  • Numerous online events are a trend that was probably accelerated by COVID.
  • With the discontinuation of Aging Science Talks hosted by Mair and Lamming there is a lack of regular weekly events. This is partly compensated for by the amazing NUS Healthy Longevity Webinar hosted by Brian Kennedy and Andrea Maier, which will continue throughout April and May with livestreams every Thursday that are uploaded to youtube afterwards. Sign-up here. Prof Henrich Jasper from the Buck institute is the upcoming speaker for the 21st of April.
  • Although not quite the same thing, Eleanor Sheekey from the "The Sheekey Science Show" regularly posts videos about aging that are quite accessible to laypeople. Lifespan.io also has very good content on youtube as does Live Long world. For example this fantastic video with Rich Miller, who needs no introduction for anyone who has done serious mouse longevity work.
  • Conferences
  • The Aging Research and Drug Discovery Meeting (ARDD2022) registration is live. The conference will be held in beautiful Copenhagen between the 29th of August and 2nd September. I have fond memories of the city which encompasses everything that is great about Europe, starting from amazing architecture, over bike infrastructure to terrific public transport. Submission deadline for short talks is the 15th of July and for posters it is the 15th of August. ARDD aims to bring together researchers, drug developers and investors. Speakers will include Vadim Gladyshev, Matt Kaeberlein, Laura Niedernhofer, Linda Partdrige, Judith Campisi, Anu Suomalainen and many more.
  • The Gordon Research Conference "Systemic Processes, Omics Approaches and Biomarkers in Aging" will take place from the 29th of May 29 until the 3rd of June. As always it is in the US and the application deadline is the 1st of May.
  • The German DGFA conference will be taking place offline from the 23rd to 24th of June 2022. Max attendance of 100. The deadline for abstract submission is 2nd May.
  • News
  • My approach is not to chase the news too much. It is well established that the daily news cycle is toxic. As far as science is concerned, if it is published in Nature, I will hear about it one way or another. On top of that I am trying to keep up with the interesting news about longevity, progress studies and futurism without having to read about the war all the time. Therefore lesswrong, twitter and the Nature editorial page are out for the last months (all too political), while reddit/longevity is in. This subreddit is an amazing resource, but only if you have the ability to filter out all the bullshit at a glance.
  • Offline events
  • We are starting the Singapore Longevity Meetup now that the COVID rules have been relaxed.

Notes from the VitaDAO Crypto meets Longevity Symposium

I (the @Aging_Scientist on twitter) will summarize a couple of the talks from the VitaDAO symposium, although fewer than I aimed for, because it took way too long to write these as is. And as always I will provide my comments on the state of the art. All errors are mine. 

Prof. Marco Demaria - University of Groningen
Heterogeneity in Senescence: from Mechanisms to Interventions
The goal is to delay multiple diseases by targeting aging. Telomeres shorten with time and cells grown in culture reach the Hayflick limit, similar things happen in vivo. We see activation of p53 and p16 expression leading to a stable generally irreversible state that is called senescence. Not all senescence (sen) is bad, because it is of course also a tumor suppressor mechanism. The factors secreted by senescent cells (SASP), are growth stimulatory, angiogenic, pro-inflammatory. This is also called sterile inflammation, which is inflammation when no pathogen is present.

We see more p16 staining in aging skin and colon, while in the brain, for example, we see elevations of GATA4 and p16.

Then Demaria talks about the, by now, classic p16 reporter mouse model where p16 was tagged with an RFP, luciferase and HSV-Tk cassette. This allows to visualize senescent cells by FACS sorting via the RFP protein, through visible light by luminescence and destroying them by ganciclovir treatment (GCV). 6 months of GCV treatment improves running distance and grip strength in mice.

Senescent cells accumulate in most tissues and they are at the center of several aging mechanisms. Treatments can be senolytics vs senomorphic, i.e. either kill the cells or reduce their harmful SASP secretion. Many drugs exist but senescent cells are heterogeneous e.g. dependent on the tissue of origin, stress type etc. so not all drugs will be universal.

Using an overlapping transcript signature from the different sen models, his team tried to predict drugs that hit all of the pathways (the candidates are proprietary). One of them administered in 3x 3-week cycles decreased luminescence expression and improved grip strength.

Senescent cell accumulation is also seen in the cochlea of aging mice and ablation leads to amelioration of hearing loss.

If high oxygen partial pressure promotes sen, can hypoxia interfere with sen? 20% oxygen is the standard cell culturing protocol whereas in the body cells are exposed to between 1 and 9% O2, with a mean of around 5%. Thus for his experiments 1% was considered hypoxia and 5% normoxia.

At 1% vs 5% although cells do enter sen they do not produce the SASP, and this effect is mediated via mTOR. Roxadustat, an EPO inducer, also reduces the SASP but the effect looks more modest to me than the effect of hypoxia. In mice the drug inhibited mTOR and increased grip strength.

During the discussion Demaria mentions that luminescence only shows senescent cells near the body surface, and their abundance is estimated at 3-5% by RFP FACS sorting. In fat it can be higher. Human sen in blood is hard to measure, usually only really feasible via biopsy or in autopsy study. As of now it seems the number of sen cells in a tissue cannot be predicted based on the characteristics of the tissue and its physiology.

Ideally one would like to copy the oxygenation levels of the original tissues when doing experiments but this is expensive to do. Other issues in experiments are too much glucose and 1D culture.

Finally, we should keep in mind there are beneficial components of SASP, while NFKB-driven targets may be bad, others may promote immune surveillance or tissue repair and we do not want to mess this up chronically. In vitro early SASP is the good one, late one is bad, but this seems like an over-simplification.

[to be continued in another post]