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Nick Stroustrup

@nstroustrup.bsky.social
1.3K followers 278 following 128 posts

A British/American group leader at @crg.eu . We study the biology of aging using molecular genetics, engineering, systems biology, and probabilistic machine learning. Lab page: lifespanmachine.crg.eu

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Nick Stroustrup @nstroustrup.bsky.social · 06/09/2026
2) Many cell types in humans don't live much longer than worms, measured from cell cycle exit until death. So I think about human physiology acting at a wide range of timescales rather than a single long timescale. We do see big cell-type specific differences in mRNA declines in mice.
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Nick Stroustrup @nstroustrup.bsky.social · 06/09/2026
Hi Ian! Two thoughts 1) we looked at worms first, where we could obtain good lifespan data. So we just don't know for mice yet. There is one previous report of increases in pol II immuno-staining in old mouse hepatocytes, but that's not the whole story I think.
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Nick Stroustrup @nstroustrup.bsky.social · 06/09/2026
Fun idea! Point: we worry about confounding mRNA degradation when samples sit out for a few moments in the lab. Counterpoint: doi.org/10.1016/j.ce...
doi.org
Redirecting
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Nick Stroustrup @nstroustrup.bsky.social · 06/09/2026
The stoichiometric ratio of mRNA to ribosomes is important! But we know there are several feedback compensatory mechanisms that modulate ribosomes' per-molecule activity, which make the situation harder to predict.
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
RNA Pol I and III are the polymerases changing under mTOR inhibition, more than Pol II, no?
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
Thank you! Please get in contact with questions or feedback.
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
I'd also like to flag a preprint from the Maharana lab, IISc, which implicates nucleotide metabolism and phase-separated condensates in age-associated RNA loss www.biorxiv.org/content/10.6... 22/22
biorxiv.org
Aging associated RNA loss impairs the dynamics of RNA and protein condensates
Altered biomolecular condensate dynamics are increasingly implicated in age-associated neurodegenerative disorders, yet the molecular principles governing these changes remain incompletely understood....
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
Our works also suggests a new strategy for interventions in aging: stabilizing youthful disequilibrium states. In particular, we’re now working on approaches to restore mRNA synthesis capacity in aged tissues. Please get in contact with questions or feedback. 21/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
The disequilbrium also explains why brief perturbations are "sticky", producing permanent decreases in lifespan. Far from equilibrium there is no homeostatic restoring force pulling Pol II back up, so early losses accumulate rather than recover. 20/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
There is more in the preprint: we model Pol II dynamics and show individuals enter adulthood in a state of Pol II abundance disequilibrium. The kinetic relaxation of this state drops Pol II abundance, limits RNA synthesis capacity and, it seems, determines lifespan. 19/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
Across 13 lifespan-altering interventions including changes to diet, body temperature, daf-16 and graded daf-2 depletion, the rate of mRNA decline predicts lifespan with a Pearson correlation of -0.96. Slower decline, longer life. 18/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
Demographically, acceleration of Pol II degradation looks exactly like aging: it produces a temporal rescaling of the entire survival curve. Rescaled hazard trajectories superimpose, suggesting that Pol II declines can set the rate of aging itself. 17/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
Aging rates and mRNA abundance declines are tightly coupled: Across these populations, mRNA abundance tracks the remaining lifespan the population has left. Deplete the pool by a given amount and you can read off the days remaining. 16/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
This excess is physiologically relevant: it is used to live long. Raising Pol II ubiquitination rates accelerates mRNA declines, shortening lifespan. Even a few hours of extra RPB-2 degradation in youth permanently limits mRNA abundance and shortens healthspan and lifespan. 15/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
So it seems that individuals enter adulthood with a four-fold excess of Pol II, high above steady state replenishment levels. 14/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
We can completely abrogate Pol II declines by knocking down the E1 ubiquitin-activating enzyme uba-1 or the 26S proteasome subunits pas-4, pbs-2, rpt-1. (though these treatments ultimately sicken animals due to toxic effects of broad inhibition of the proteosome). 13/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
We find that Pol II decreases are driven by ubiquitin-mediated proteasomal degradation: during adulthood, Pol II subunits are degraded faster than they are synthesized. 12/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
We find that nuclear Pol II drops several-fold in abundance with age. This is a somatic phenomenon–the germline seems to maintain Pol II just fine. Somatic declines in Pol II begin at the start of adulthood, a time when individuals still look young and vigorous. 11/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
We hypothesized mRNA declines might be a symptom of declines in mRNA synthesis rate. To look at this, we built an RNA Pol II in vivo reporter that lets us measure the abundance of RNA Pol II in the nucleus across adulthood. 10/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
Obviously, the abundance of mRNAs is important for cells for many reasons–for example it partially determines much protein a cell can make. Why is absolute mRNA abundance dropping so much during aging? 9/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
We went back and also found some previous reports of mRNA decreases: in a super cool paper Davie, Janssens et al.'s single cell atlas that found RNA depletion in the Drosophila brain: pmc.ncbi.nlm.nih.gov/articles/PMC... 8/22
pmc.ncbi.nlm.nih.gov
A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain
The diversity of cell types and regulatory states in the brain, and how these change during aging, remains largely unknown. We present a single-cell transcriptome atlas of the entire adult Drosophila ...
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
We first saw this in our C. elegans data, but then went looking and confirmed that similar decreases exist in mouse single-cell atlases: e.g. we see a >2-fold decrease in aorta, >3-fold in non-myeloid brain by 18-24 months. 7/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
But if we perform absolute quantification using short-read RNA-seq with ERCC spike ins, or native long-read sequencing (thanks @evamarianovoa + team for the nanopore data) we see a huge effect. 6/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
This phenomenon is invisible to standard computational practice. RNA-seq library-size normalization assumes every sample contains equal amounts of mRNA, and rescales libraries to enforce this assumption. 5/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
We confirmed these results in single-cell transcriptomes: RNA depletion is happening in individual cells, across most cell types. On an absolute scale, aged cells seem to be running low on mRNA. 4/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
The effect is fairly dramatic in both nematodes and mice. For example: a young adult nematode (equivalent to a teen-ager) contains ~700 million mRNA molecules total. This drops eight-fold by old-age. 3/22
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
The project was spearheaded by @adelcarmenf.bsky.social with contributions from everyone in my group at @crg.eu . You can read the preprint here: www.biorxiv.org/content/10.6... 2/22
biorxiv.org
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Nick Stroustrup @nstroustrup.bsky.social · 05/09/2026
Did you know that the cells of old animals contain much less mRNA than the cells of young ones? Let me share with you some results from an ongoing project in the lab, where we are finding that a progressive depletion of total mRNA abundance is a crucial part of aging 1/22
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Böke Lab @bokelab.bsky.social · 12/08/2026
What does an ovary actually look like as it ages—one oocyte at a time? We mapped >85,000 oocytes in >100 intact mouse ovaries, in 3D, across the reproductive lifespan. And the ovary turned out to be much more organized than we expected. 🧵 1/5 www.nature.com/articles/s43...
nature.com
Three-dimensional mapping of intact ovaries reveals the aging dynamics of the ovarian reserve - Nature Aging
The spatiotemporal dynamics of the depletion of the ovarian reserve remain incompletely understood. Combining whole-ovary imaging, AI and modeling, the authors mapped over 85,000 mouse oocytes and fou...
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Markus Höpfler @markushopfler.bsky.social · 08/05/2026
We're hiring! Join our growing team at the @crg.eu as a postdoc. Curious about how mRNA translation and decay cross-talk? We're looking for a postdoctoral researcher to lead a project in the field of RNA biology and gene regulation. Apply here: recruitment.crg.eu/content/jobs... Please share!
recruitment.crg.eu
Postdoc in the Dynamics of Protein Synthesis and RNA Decay Lab | CRG Online Recruitment Portal
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Nick Stroustrup @nstroustrup.bsky.social · 09/06/2026
wapo.st/43SQW6q
wapo.st
Pope Leo to bless new tower at Sagrada Família, Gaudí’s unfinished masterpiece
The basilica, designed by Antoni Gaudí, becomes the world's tallest church with the inauguration of its central spire — the 566-foot-high Tower of Jesus Christ.
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Nick Stroustrup @nstroustrup.bsky.social · 10/04/2026
How do wealthy parents help their offspring? By giving them ribosomes! Optimal ribosome provisioning is key to fast development in unpredictable environments. The fastest path to ribosomal wealth in nematodes is a maternal inheritance. Happy we could play a small part in this fascinating work.
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Nick Stroustrup @nstroustrup.bsky.social · 28/03/2026
Do we know the efficacy of the new vaccine candidates?
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Lukas Röseler @aufdroeseler.bsky.social · 26/03/2026
-- New Open Research Game -- I reached the rank of Asst. Prof in #TenureRun! 🎓 I published 98 papers and paid $115.000 in APCs to publishers. My grant money is gone and I am exhausted. 💸 How far can you make it? Play now at forrt.org/TenureRun/
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Nick Stroustrup @nstroustrup.bsky.social · 06/03/2026
Second this!
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Nick Stroustrup @nstroustrup.bsky.social · 02/03/2026
And of course, I remember his kindness of taking me on as a clueless engineering student and getting me a start in genetics. I only worked with him for a year, more than twenty years ago, but I still think about things he said. David Botstein, 1942 - 2026. www.online-tribute.com/DavidBotstein
online-tribute.com
David Botstein | 1942 - 2026 | Online-Tribute.com
David was a beloved husband, father, brother, scientist, teacher, mentor, musician, friend, who touched the lives of thousands. David’s wide-ranging scientific career spanned decades with a legacy o…
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Nick Stroustrup @nstroustrup.bsky.social · 02/03/2026
So while David is often remembered for his field-defining technological advances, e.g. restriction fragment linkage mapping and microarrays, what I remember most is the way he spoke and thought--integrating complex mechanistic detail with broader ideas about yeast physiology and metabolism.
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Nick Stroustrup @nstroustrup.bsky.social · 02/03/2026
David was super smart and super direct, with a insistence on clear thinking that permeated everything he did. He could speak about "big picture" dynamical properties of cells, but he also had an encyclopedic memory-- ask him about any yeast gene and he'd tell you about it in fascinating detail.
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Nick Stroustrup @nstroustrup.bsky.social · 02/03/2026
hoping to learn what all the excitement was about, at the new genomics institute they'd just built on campus. I cold-emailed David looking for work, and a week later I was sitting in his office, learning about the principles of chemostats. I think I still have the little notebook drawing he made.
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Nick Stroustrup @nstroustrup.bsky.social · 02/03/2026
It's very sad to learn of David Botstein's passing. I worked in David's lab as an undergraduate--one of the most formative periods of my academic life and probably the biggest reason I work in biology today. I vividly remember my first meeting with David. I was a 3rd year engineering student,
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Nick Stroustrup @nstroustrup.bsky.social · 27/02/2026
Very cool!
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Javier Apfeld @javierapfeld.bsky.social · 28/01/2026
We found 24 neuron classes that are excited or inhibited by environmental H2O2, spread across the nose, mouth, and inner pharynx. Different neurons trigger at different H2O2 levels (from 1 µM early warning to >1 mM lethal), and many adapt, so responses encode dose + recent history. 7/
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Nick Stroustrup @nstroustrup.bsky.social · 25/02/2026
I am curious what counterfactual unsettling egg shapes you have in mind!
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Nick Stroustrup @nstroustrup.bsky.social · 18/02/2026
I was today years old when I discovered that "npj Aging" and "Nature Aging" are separate journals, despite being published with identical titles by Springer Nature!
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Mark Peifer (He, him) @peiferlabunc.bsky.social · 17/02/2026
Please consider joining us--the new restrictions on academic freedom are coupled with a move to make all syllabi public and secretly record our classes--UNC's status as a top public university is at stake
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Nicole Gerlach @ngerlach.bsky.social · 12/02/2026
I knew about the downward part, but not the upward part, and now I'm not okay.
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EMBO @embo.org · 11/02/2026
Happy International Day of Women and Girls in Science! 🧪 Don't forget to send in your nominations for the FEBS | EMBO #WomenInScience Award. Deadline: 15 May Read more: www.embo.org/the-embo-communities/f… #award
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Nick Stroustrup @nstroustrup.bsky.social · 05/02/2026
www.nytimes.com/2026/02/04/o...
nytimes.com
Opinion | I’m the Prime Minister of Spain. This Is Why the West Needs Migrants.
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Nick Stroustrup @nstroustrup.bsky.social · 02/02/2026
sunday afternoon family collaboration
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Monica Bettencourt-Dias @monicabettencourt.bsky.social · 23/01/2026
📣 Please spread: we’re hiring a Lab Manager! It is a critical position in our new lab. As our lab moves to Barcelona and joins the @crg.eu, we’re looking for a Lab Manager to help build the lab and set the lab atmosphere. 🔗 Apply here 👉 recruitment.crg.eu/content/jobs...
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