Jérôme Salignon

Can we measure & shift a cell’s age? Meet Pasta, a plug-and-play transcriptomic clock that flags perturbations that ↑ (cancer therapy) or ↓ (regenerative medicine) biological age. doi.org/pqhh
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Can we measure & shift a cell’s age? Meet Pasta, a plug-and-play transcriptomic clock that flags perturbations that ↑ (cancer therapy) or ↓ (regenerative medicine) biological age. doi.org/pqhh #aging #AI 🧵 bsky.app/profile/jero...

Pasta, an age-shift transcriptomic clock, maps the chemical and genetic determinants of aging and rejuvenation As the prevalence of age-related diseases rises, understanding and modulating the aging process is becoming a priority. Transcriptomic aging clocks (TACs) hold great promise for this endeavor, yet mos...

Can we measure & shift a cell’s age? Meet Pasta, a plug-and-play transcriptomic clock that flags perturbations that ↑ (cancer therapy) or ↓ (regenerative medicine) biological age. doi.org/pqhh #aging #AI 🧵 bsky.app/profile/jero...

GitHub - jsalignon/pasta: P̲redicting a̲ge-s̲hift from t̲ranscriptomic a̲nalyses P̲redicting a̲ge-s̲hift from t̲ranscriptomic a̲nalyses - jsalignon/pasta

📦 Pasta R package + tutorials → github.com/jsalignon/pasta • Preprint doi.org/pqhh • Feedback welcome!
🙏 Cooked with 💙 by @fedpie.bsky.social ChristianRiedel, PatriciaMarques, MariaTsiokou, at @ki.se @stockholm-uni.bsky.social #Bioinformatics #Longevity

🧬Integration with DepMap highlighted the pivotal role of epigenetic regulation and splicing pathways in shaping cellular responses to pro-rejuvenating signals, and of mitochondrial translation and type I interferon in responses to pro-aging signals. #RegenerativeMedicine

Horizontal bar chart: anti-cancer drugs enriched among pro-ageing hits; AML bar tallest, most other cancers show similar trend.

💊 FDA-approved anti-cancer drugs were highly enriched in Pasta’s pro-aging hits—strongly supporting the idea that chemotherapy works by aging cancer cells. This data-driven approach may help uncover safe, cancer-specific therapies. #Chemotherapy

Twin bar charts: ageing compounds (olive bars) enriched for senescence; rejuvenating compounds (navy) enriched for reprogramming.

💻 Screening 3 million CMAP profiles revealed pro-aging and pro-rejuvenation genetic and chemical perturbations. Importantly, these two sets were enriched in known pro-senescence and pro-stemness factors, respectively.

🩺In TCGA tumors, Pasta’s scores correlated better with tumor grade than chronological age, indicating its value as a biological age predictor. Pasta’s scores were also predictive of patient survival for certain cancers. #CancerResearch

Two scatter plots: replicative senescence shows age score rising with day; OSKM reprogramming shows score dropping over time.

🔍A novel age-shift modeling strategy yielded more accurate and biologically meaningful predictions, based on p53-related genes, than traditional regression models. Pasta also cleanly separated senescence, quiescence, stemness & differentiation in static and dynamic settings.

Dot plot: red (Pasta) vs purple (MultiTIMER) Pearson r values across 14 datasets—Pasta higher in 11/14.

📊 Trained on 21 heterogeneous datasets to predict relative age, Pasta was designed to be broadly applicable to many kinds of transcriptomic data (i.e., microarrays, L1000…). It outperformed other RNA-Seq-specific tools without requiring reprocessing or batch correction.

clock face built from pasta shapes with Vitruvian-man—logo for Pasta transcriptomic ageing clock.

Can we measure & shift a cell’s age? Meet Pasta, a plug-and-play transcriptomic clock that flags perturbations that ↑ (cancer therapy) or ↓ (regenerative medicine) biological age. doi.org/pqhh #aging #AI 🧵👇

🚨 Pre-print alert! 🚨

We generated chromosome-scale diploid genome assemblies for the widely used fibroblast lines BJ and IMR-90.

These models of replicative senescence and telomere shortening now have fully resolved telomeres, subtelomeres, and centromeres. 🧬

🧵👇

Great work! Congrats!

Emerging insights in senescence: pathways from preclinical models to therapeutic innovations - npj Aging npj Aging - Emerging insights in senescence: pathways from preclinical models to therapeutic innovations

Emerging insights in senescence: pathways from preclinical models to therapeutic innovations 👩‍🔬🧪🔬🥼👨‍🔬 #senescence #SASP #ageing #inflammation #NephSky #CardioSky #Senescent

Full details 👇 ✨️

www.nature.com/articles/s41...