Biology subjects

Pietrocola, F.

Publications and source records attributed to Pietrocola, F..

3 recordsLinked to original sources

bioRxiv2026

SENOMORPHIC EFFECT OF GENETIC AND CHEMICAL PARTIAL REPROGRAMMING

Partial reprogramming has emerged as a promising strategy to ameliorate aging phenotypes, yet its cellular targets and mechanisms remain poorly defined. Cellular senescence is a central hallmark of aging and a plausible mediator of reprogramming-induced rejuvenation. Here we show that genetic and chemical partial reprogramming act directly on senescent cells without restoring proliferative capacity. OSKM expression or a reduced two-compound regimen, tranylcypromine and RepSox (2c), attenuates senescence-associated secretory activity, restores mitochondrial homeostasis and apoptotic priming, and improves functional and inflammatory parameters in aged mice, establishing senomorphic, identity-preserving reprogramming as a potentially safer aging intervention.

cell biology↗

bioRxiv2025

Pasta, an age-shift transcriptomic clock, maps the chemical and genetic determinants of aging and rejuvenation

With the growing burden of age-related diseases, understanding and modulating the aging process has become a priority. Transcriptomic aging clocks (TACs) can track biological age but remain limited by platform dependence, tissue specificity, or restricted accessibility. To address this, we developed Pasta, a robust and broadly applicable human TAC built using a novel age-shift learning framework. Pasta accurately predicted relative age across diverse tissues, data types, including bulk and single-cell RNA-Seq as well as microarray data, and species. Its predictions aligned with senescent and stem-like cellular states, with model coefficients enriched for p53 and DNA damage response pathways. Pastas age scores correlated with tumor grade and patient survival in several cancer types, indicating potential clinical relevance. Applied to the Connectivity Map L1000 dataset, Pasta identified both established and previously unrecognized age-modulatory compounds and genetic perturbations, highlighting mitochondrial translation and mRNA splicing as key determinants of cellular propensity for aging and rejuvenation, respectively. Experimental validation confirmed pralatrexate as a potent senescence inducer and piperlongumine as a rejuvenating agent. Together, these findings establish Pasta as a versatile and accessible tool for aging research and therapeutic discovery.

bioinformatics↗

bioRxiv2022

Induction of senescence renders cancer cells highly immunogenic

Cellular senescence is a stress response that activates innate immunity. However, the interplay between senescent cells and the adaptive immune system remains largely unexplored. Here, we show that senescent cells display enhanced MHC class I (MHC-I) antigen processing and presentation. Immunization of mice with senescent syngeneic fibroblasts generates CD8 T cells reactive against both normal and senescent fibroblasts, some of them targeting senescence-associated MHC-I-peptides. In the context of cancer, we demonstrate that senescent cancer cells trigger strong anti-tumor protection mediated by antigen-presenting cells and CD8 T cells. This response is superior to the protection elicited by cells undergoing immunogenic cell death. Finally, induction of senescence in patient-derived cancer cells exacerbates the activation of autologous tumor-reactive CD8 tumor-infiltrating lymphocytes (TILs) with no effect on non-reactive TILs. Our study indicates that immunization with senescent cancer cells strongly activates anti-tumor immunity, and this can be exploited for cancer therapy. STATEMENT OF SIGNIFICANCEOur study shows that senescent cells are endowed with a high immunogenic potential, superior to the gold standard of immunogenic cell death. The induction of senescence in cancer cells can be exploited to develop efficient and protective CD8-dependent anti-tumor immune responses.

cancer biology↗