Efficacy of longevity interventions in C. elegans is determined by early life activity of RNA splicing factors
Efficacy of longevity interventions in C. elegans is determined by early life activity of RNA splicing factors
Abstract Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using in vivo mini gene reporters in isogenic C. elegans, we show that alternative splicing of mRNAs related to lipid metabolism in young animals is coupled to subsequent life expectancy. Further, activity of RNA splicing factors REPO-1 and SFA-1 early in life modulates effectiveness of specific longevity interventions via POD-2/ACC1 and regulation of lipid utilization. In addition, early inhibition of REPO-1 renders animals refractory to late onset suppression of the TORC1 pathway. Together these data suggest that activity of RNA splicing factors and the metabolic landscape early in life can modulate responsiveness to longevity interventions and may explain variance in efficacy between individuals. One Sentence SummaryEfficacy of pro-longevity interventions in C. elegans is determined by the activity of splicing factors and the lipid metabolic landscape early in the life of the individual.
Heintz Caroline、Perez-Matos Maria C.、Mistry Meeta、Sharma Arpit、Sehgal Rohan、Lanjuin Anne、Wang Meng C.、Mair William B.、Piper Mary E.、Howell Porsha、Mutlu Ayse Sena、Dutta Sneha、Smith Hannah J.
Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard UniversityDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard UniversityHarvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public HealthDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard UniversityDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard UniversityDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard UniversityHuffington Center on Aging, Baylor College of Medicine Howard Hughes Medical Institute, Baylor College of Medicine||Howard Hughes Medical Institute, Baylor College of MedicineDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard UniversityHarvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public HealthDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard UniversityHuffington Center on Aging, Baylor College of Medicine Howard Hughes Medical Institute, Baylor College of MedicineDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard UniversityDepartment of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Harvard University
分子生物学遗传学生物科学现状、生物科学发展
Heintz Caroline,Perez-Matos Maria C.,Mistry Meeta,Sharma Arpit,Sehgal Rohan,Lanjuin Anne,Wang Meng C.,Mair William B.,Piper Mary E.,Howell Porsha,Mutlu Ayse Sena,Dutta Sneha,Smith Hannah J..Efficacy of longevity interventions in C. elegans is determined by early life activity of RNA splicing factors[EB/OL].(2025-03-28)[2025-06-12].https://www.biorxiv.org/content/10.1101/2021.11.01.466772.点此复制
评论