Longevity Papers 2025-04-17

Paper Title: Boosting Cellular Longevity Through Intracellular ATP Modulation Authors: Naci Oz, Hetian Su, Praveen Patnaik, Derek C. Prosser, Vyacheslav M. Labunskyy, Rohil Hameed, Vadim N. Gladyshev, Nan Hao, Alaattin Kaya Institution: University of Virginia, University of California San Diego, Boston University, Harvard Medical School Date: April 16, 2025 Link: https://www.biorxiv.org/content/10.1101/2025.04.14.648769v1 Key Findings: Engineered yeast with a parasitic ATP transporter (NTT1) showed ATP depletion shortens lifespan, while supplementation extends it. Dual mechanisms: mitochondrial suppression (catabolism) and extracellular ATP sensing (MAPK activation). 40% lifespan extension in NTT1 yeast (p=4.03E-18), but high-dose ATP caused toxicity in mitochondrial-competent cells (Fig 6B). Limitations: Yeast models lack human aging complexity (e.g., inflammation, systemic decline). Next Steps: Validate in mammals, identify ATP-sensing receptors, test combinatorial therapies (e.g., ATP + rapamycin). Paper Title: HDAC11 Deficiency Regulates Age-Related Muscle Decline and Sarcopenia Authors: Renato Odria, Aina Cardús, Clara Gomis-Coloma, Ulalume Hernández-Arciga, Ceda Stamenkovic, Shweta Yadav Institution: Institut d'Investigació en Ciències de Salut Germans Trias i Pujol, Spain Date: April 12, 2025 Link: https://pubmed.ncbi.nlm.nih.gov/40220154/ Key Findings: HDAC11-deficient aged mice resisted sarcopenia: 26% larger type IIb muscle fibers (p less than 0.0001), 55% fewer lipid droplets (Fig 6B), and ω-6/ω-3 ratio reversal (3.5 → 1.8). 50% increase in PAX7⁺ satellite cells post-injury, suggesting enhanced regeneration. Limitations: Small cohort (n=19 KO mice), survival bias (0% mortality vs. 27% in WT), no dietary controls. Next Steps: Muscle-specific KO models, lysine-myristoylation proteomics, in vivo electrophysiology. Comparative Insights: Both studies target metabolic pathways (ATP/HDAC11) but lack translational rigor. Yeast highlights energy flux; mice emphasize lipid/metabolic reprogramming. Critical gap: Human relevance unproven. Prioritize muscle-specific and dose-controlled studies.