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Pasta, a Versatile Transcriptomic Clock, Maps the Chemical and Genetic Determinants of Aging and Rejuvenation
Jérôme Salignon1,2, Maria Tsiokou3, Patricia Marqués3
1Department of Medicine Huddinge, Karolinska Institute, Huddinge, Sweden.
Researchers developed Pasta, a novel transcriptomic aging clock (TAC), to accurately measure biological age across various human tissues and data types. This tool aids in identifying age-modulating compounds and understanding aging mechanisms for therapeutic discovery.
Area of Science:
- Gerontology
- Bioinformatics
- Molecular Biology
Background:
- Age-related diseases pose a significant global health challenge.
- Transcriptomic aging clocks (TACs) offer insights into biological age but face limitations like platform dependence and tissue specificity.
Purpose of the Study:
- To develop a robust, broadly applicable human TAC named Pasta.
- To address limitations of existing TACs by creating a versatile tool for aging research.
Main Methods:
- Developed Pasta using a novel 'age-shift' learning framework.
- Validated Pasta's predictions across diverse tissues and data types (bulk/single-cell RNA-Seq, microarray).
- Analyzed model coefficients for pathway enrichment (p53, DNA damage response).
Main Results:
- Pasta accurately predicted relative biological age across various human tissues and data types.
- Age scores correlated with cellular states (senescent, stem-like) and cancer characteristics (grade, survival).
- Identified age-modulatory compounds and genetic perturbations, highlighting mitochondrial translation and mRNA splicing roles.
Conclusions:
- Pasta is a versatile and accessible tool for aging research and therapeutic discovery.
- Identified pralatrexate as a senescence inducer and piperlongumine as a rejuvenating agent.
- Established key molecular pathways influencing cellular aging and rejuvenation.
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