Antebi Lab

rdcu.beVitamin B12 alleviates spliceosomopathy via phospholipid remodelingNature Communications - The authors use a Caenorhabditis elegans model of Verheij syndrome, caused by mutations in the splicing factor PUF60, and show that Vitamin B12 can rescue the phenotype.

1/8 🚨 Out now in @NatureComms 🚨 A vitamin mitigates symptoms of a rare genetic disease. Verheij syndrome is caused by mutations in the mRNA splicing factor PUF60. Vitamin B12 restores normal development in our disease model, the worm C. elegans. rdcu.be/fyIgM

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.

Big thanks to all authors, @mpiage.bsky.social, @cecad.bsky.social #Celegans #Splicing #Metabolism #VitaminB12 #Phospholipids #RareDisease #NatureCommunications

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.

7/8 What about humans? Decreasing PUF60 in human cells alters splicing of one-carbon and phospholipid genes. Verheij patients have ~85% lower methionine and triglycerides with longer, more unsaturated fatty acids in their plasma, a signature we also see in the worm.

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.

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.

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… 🤔

MPI for Biology of Ageing

3/8 Two screens, one answer. We screened 7,970 E. coli deletion strains and ~20,000 mutagenized worm genomes for loss of rescue. In bacteria we found genes for vitamin B12 transport, in worms we identified genes of the one-carbon metabolism. Both roads converged in vitamin B12.

Antebi Lab reposted

@mpiage.bsky.social

nature.comVitamin B12 alleviates spliceosomopathy via phospholipid remodeling - Nature CommunicationsThe authors use a Caenorhabditis elegans model of Verheij syndrome, caused by mutations in the splicing factor PUF60, and show that Vitamin B12 can rescue the phenotype.

📢 Publication alert New study from the @antebilab.bsky.social on Verheij syndrome, a rare genetic developmental disorder linked to defects in RNA splicing. www.nature.com/articles/s41...

11 June

We recently said goodbye to our wonderful PhD-student-turned-postdoc Klara. From C. elegans, mTOR and steroid metabolism to gardening and other new adventures. Your resilience is exemplary and your spirit contagious. We will miss you! 🪱🌿🌼 #Celegans #mTOR #goodbye

22 May

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!

micropublication.orgDeconvolution of Single-Organism Omics Resolves Cellular and Tissue Dynamics during Aging | microPublication

4 May

🚨Publication @micropub7n.bsky.social www.micropublication.org/journals/bio... PoC study by Y. Park: deconvolving the C. elegans proteome to organ- & tissue-level ageing trajectories expands the use of single-worm proteomics data as a powerful tool to study dynamic cellular changes during ageing.

27 Mar

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!

11 Mar

🥳🎓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

1/4 Our preprint “Modulation of the RNase P/MRP complex and mitochondrial ribosome enhances cytosolic ribosome coordination and sustains longevity” is now live @biorxivpreprint.bsky.social 📄 #agingbiology #ribosome 👉https://www.biorxiv.org/content/10.64898/2026.02.23.707525v1

3/4 Using C. elegans, we find that loss of the nucleolar regulator, ncl-1/TRIM2-3, disrupts ribosomal balance, leading to proteostasis defects and premature aging. Ribosomal biogenesis becomes uncoordinated, causing imbalanced ribosomal components and translational dysfunction.

4/4 Perturbing either the mitochondrial ribosome or the RNase P/MRP complex restores ribosomal balance & extends lifespan, suggesting that improving ribosome coordination, rather than reducing overall biogenesis, is a promising avenue to support cellular health in ageing.

2/4 In this study, we investigate fundamental questions about ribosome biology and ageing. While ribosomes are essential to life, how their assembly and coordination change with age, and how that contributes to ageing, remains poorly understood.

24 Dec 2025

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

20 Dec 2025

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

doi.orgVitamin B12 alleviates Verheij syndrome-like defects via phospholipid remodeling in a C. elegans PUF60 spliceosomopathy modelVerheij syndrome (VRJS) is a rare genetic disorder caused by mutations in the poly(U)-binding splicing factor 60 (PUF60), a core component of the spliceosomal complex. VRJS triggers multiple congenita...

8 Oct 2025

🚨New @biorxivpreprint: We model the splicing factor disease Verheij syndrome using C. elegans. Disruption of methionine and phospholipid metabolism drives growth defects; vitamin #B12 restores metabolic balance and rescues development! #metabolism #Celegans #RNAsplicing doi.org/10.1101/2025...

4 Sept 2025

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

18 Aug 2025

Our lab's BBQ last Friday was a blast! Meticulous research revealed the ultimate anti-aging formula: juicy burgers and great company! 🍔👩‍🔬 #AgingResearch

7 July 2025

🏆⚽️ 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

nature.comA TFEB–TGFβ axis systemically regulates diapause, stem cell resilience and protects against a senescence-like state - Nature AgingNonninger et al. identify the TFEB–TGFβ signaling axis as a regulator of stem cell resilience that protects against a senescence-like state during the adult diapause in Caenorhabditis elegans, a mecha...

1/7 🚨Out now @nataging.nature.com 🚨 We identified a genetic network of TFEB, TGFβ and NOTCH signaling regulating stem cell resilience, rejuvenation & senescence in C. elegans in response to nutrient cues, with conservation across taxa. www.nature.com/articles/s43...

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.

7/7 In sum, hlh-30 mutation causes misalignment of nutrient cues and growth signaling, resulting in DNA damage & cellular senescence, which abrogates stem cell and organismal longevity. Cellular senescence is an evolutionarily ancient response to damage conserved even in C. elegans.

4/7 Genetic suppressor screens reveal mutations that disrupt TGFβ, cGMP and insulin/IGF signaling potently reverse hlh-30/TFEB collapse.

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.

2/7 Worms fasted in late larval development progress to a sleep-like quiescent state called the adult reproductive diapause (ARD) and can survive for months without food. Upon refeeding they undergo restoration, regenerating germline, soma and reproduce.

Cologne Graduate School of Ageing Research

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.

Antebi Lab reposted

@cga-age.bsky.social

12 June 2025

🎊Today, we're excited to celebrate the graduation of our amazing 13 students from the CGA Class of 2021! We’re so proud of all their accomplishments. 🎓Come join us now as they present their PhD projects at the 13th CGA Graduate Symposium. And, of course, we can’t wait for the dinner party tonight!🍾

11 June 2025

🥳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! 🥂

Cologne Graduate School of Ageing Research

5 June 2025

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

Antebi Lab reposted

@cga-age.bsky.social

6 May 2025

👩‍🎓We're thrilled to share some wonderful news! Klara Schilling from the CGA Class of 2020 successfully defended her PhD thesis today! Klara, we hope you're enjoying some well-deserved celebrations right now! 🥂🎊 @mpiage.bsky.social @antebilab.bsky.social

biorxiv.orgResilience and restoration from fasting-refeeding mediated by a nutrient-regulated linker histoneIntermittent fasting and fasting-refeeding regimens can slow biological aging across taxa[1][1]. Shifts between fed and fasted states activate ancient nutrient-sensing pathways which alter cellular an...

Preprint alert @biorxivpreprint! We are excited to share our latest study led by @kkawamura13.bsky.social @annadiederich01.bsky.social in collaboration with & C. Demetriades Lab & @muellerrom.bsky.social Lab www.biorxiv.org/content/10.1...

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.

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.

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.

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.

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.