Antebi Lab
@antebilab
Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing
8/8 In sum, we identify a metabolic bottleneck underlying PUF60 deficiency and show that vitamin B12 rescues Verheij-like phenotypes. We propose that splicing diseases may be metabolically tractable and will further investigate B12 supplementation as a therapeutic strategy.
6/8 Downstream, mutants switch on the integrated stress response & shut down mTORC1. B12 reverses both & blocking mTOR activation abolishes the rescue. Similar responses arise in mutants of the splicing factor prp-19/PRPF19, suggesting this metabolic route as a conserved target.
5/8 We also found an upstream factor. rnp-6 mutants mis-splice nhr-114/HNF4, a transcription factor for one-carbon and lipid metabolism, which retains intron 4. Forcing the intron in by CRISPR: worms phenocopy rnp-6 mutants. Deleting it: rnp-6 mutants resemble healthy wild type.
4/8 Why B12? The rnp-6/PUF60 mutants run low on methylation capacity (SAM/SAH) and on the lipid phosphatidylcholine (PC), with phosphatidylethanolamine piling up. B12 refuels methionine, then SAM, then PC. Supplementing methionine or choline does the same job.
2/8 Serendipitously, we found that rnp-6/PUF60 mutant worms stay small and develop slowly on the standard OP50 diet, but reach full size on the K12 E. coli strain BW25113. Something in the food was compensating for a compromised spliceosome… 🤔
Last week we said goodbye to one of the founding members of our lab. Birgit joined the lab as a postdoc @molgen.mpg.de & rejoined when the lab moved to the @mpiage.bsky.social. She did incredible science, served as our lab manager & trained generations of junior scientists. You will be missed!
Today we said farewell to our PhD student turned postdoc Eugene Ballhysa. The energy in his conversations matched his enthusiasm for science🔬🐟We’ll miss you—and we wish you all the best for the road ahead!
🥳🎓Congratulations to Maja on an outstanding master’s thesis defense. Your rigor, perseverance, and dedication are exemplary. Excited to see what comes next.🌟 #GradLife #MastersDefense
Our tiny market of longevity dreams—lab merch, publications, Flammkillifish and ‘rejuvenation’ tonics—won🥈in the annual window decoration contest!🥇to the @inahuppertz.bsky.social and Scheiblich labs chasing the Grinch for their data. Backups, people! 💾 #LabLife #AgingResearch #FestiveScience
From worms to humans, our lab gathered for the annual festive brunch and Secret Santa—because community is the best longevity intervention🎁🎄🫶 #LabLife #Longevity #ScienceCommunity
Eugene, Victoria & Tabrez are just back from Copenhagen🇩🇰 #ARDD2025! Kazuto (@kkawamura13.bsky.social) took the stage to share his insights on fasting-refeeding and age-restoration. ⌛️🍽️ Turns out, the fountain of youth might just be a histone away!🪱🔬 #Rejuvenation #AgingResearch
Our lab's BBQ last Friday was a blast! Meticulous research revealed the ultimate anti-aging formula: juicy burgers and great company! 🍔👩🔬 #AgingResearch
🏆⚽️ A huge shoutout to the Antebi lab's team 'C(riminally) elegant' for winning the human Foosball match at the CECAD Summer Party @cecad.bsky.social! Your elegance on the field is unmatched!💪 #LabLegends #Foosball
6/7 Together with Manuel Serrano’s group, we found that TFEB loss reduces survivorship in both embryonic and cancer diapause, and that TFEB and TGFβ signaling are regulated during diapause. Hence, targeting TFEB might undermine cancer dormancy and prevent relapse in vivo.
5/7 HLH-30 downregulates TGFβ signaling from neurons to germline stem cells, promoting stem cell quiescence upon ARD to safeguard against cellular senescence. Mutations in TGFβ signaling prevent senescence upon hlh-30/TFEB loss, restoring resilience and reproductive competence.
4/7 Genetic suppressor screens reveal mutations that disrupt TGFβ, cGMP and insulin/IGF signaling potently reverse hlh-30/TFEB collapse.
3/7 hlh-30/TFEB is a master regulator of ARD, whose loss leads to complete collapse during ARD and recovery. Mutants arrest in a novel senescent-like state never described before in worms, and germline stem cells show features strikingly similar to mammalian cellular senescence.
🥳Congratulations @annadiederich01.bsky.social for successfully defending your master's thesis. Great collaboration with the Demetriades Lab. We are thrilled to also accompany you on your PhD journey. To many more interesting findings! 🥂
Last week we said goodbye to our PhD student-turned-postdoc Tim! We are sad to see you go, but confident that you will do great things wherever your journey takes you next! 👨🔬#Farewell
To sum up, hil-1/H1-0 is a critical mediator that reprograms epigenetic state in response to metabolic inputs. We believe studying refeeding after a prolonged fast can help elucidate adult organismal rejuvenation in a natural context.
Looking at the flip side of the coin, hil-1 is an equally important regulator of the refeeding response. Further enhancing the natural downregulation of hil-1 during refeeding by RNAi improved restoration, as measured by body size regrowth and functional muscle regrowth.
Loss of HIL-1/H1.0 reduced survival during prolonged fasting in C. elegans worms and in a human in-vitro model for nutrient restriction, suggesting that this epigenetic factor has a key role in promoting adaptation to quiescent and low nutrient states.
What regulates the fasting-refeeding switch? Unexpectedly, we found a linker histone regulated by nutrients and mTOR signaling, that promotes resilience during fasting and restoration upon refeeding. Its regulation is evolutionarily conserved, including in fasted human patients.
Rejuvenation of gene expression patterns also occurred in refed killifish, suggesting refeeding as a time window for age restoration from simple worms to vertebrates!
Can organisms reverse their biological age? In the worm C. elegans we found striking biological age restoration during refeeding after a prolonged fast, based on aging clocks! Fasting is usually linked to anti-aging, but our study points to the age-restorative role of refeeding.