Influence of Post-transcriptional Gene Regulation on Cell Senescence and Aging

$4,532,254ZIAFY2025AGNIH

National Institute On Aging

Investigators

Linked publications, trials & patents

Paper 39143693 Paper 38769646 Paper 38721764 Paper 38637019 Paper 38587072 Paper 37728586 Paper 37462262 Paper 37237280 Paper 37154037 Paper 37097759 Paper 37086265 Paper 37083495 Paper 37009481 Paper 36577843 Paper 36136759 Paper 35714586 Paper 35467654 Paper 35429111 Paper 35394839 Paper 35349590 Paper 34181735 Paper 34102611 Paper 33731671 Paper 32300964 Paper 32277935 Paper 32160592 Paper 32041821 Paper 31251810 Paper 31144457 Paper 30936558 Paper 30784348 Paper 30272251 Paper 30086537 Paper 30035254 Paper 29988036 Paper 29967290 Paper 29880812 Paper 29592859 Paper 29563610 Paper 29516680 Paper 29327503 Paper 29054597 Paper 28877934 Paper 28838538 Paper 28684423 Paper 28502821 Paper 28472763 Paper 28472401 Paper 28445677 Paper 28247949 Paper 28080204 Paper 27928058 Paper 27824314 Paper 27812869 Paper 27307117 Paper 26992231 Paper 26990999 Paper 26687548 Paper 26546448 Paper 26391950 Paper 26331977 Paper 26253535 Paper 26215566 Paper 26177105 Paper 26141605 Paper 25640162 Paper 25543668 Paper 25366541 Paper 25123665 Paper 25047833 Paper 24326307 Paper 24165399 Paper 23904268 Paper 23840442 Paper 23837869 Paper 23758631 Paper 23555285 Paper 23178169 Paper 23155001 Paper 23117626 Paper 23066106 Paper 22907752 Paper 22841487 Paper 22813890 Paper 22785201 Paper 22708488 Paper 22617883 Paper 22547681 Paper 22395603 Paper 22355589 Paper 22306790 Paper 22201738 Paper 22072795 Paper 21935886 Paper 21480233 Paper 21317874 Paper 21209379 Paper 20498276 Paper 20351400 Paper 20157551

Abstract

Changes in gene expression patterns are a hallmark of the aging process. Important insight into the mechanisms controlling such gene expression programs has come from the study of replicative senescence of cultured cells (e.g., human diploid fibroblasts), which recapitulates many features of cells from aging individuals. This Project has traditionally studied changes in RNA-binding protein (RBP) expression and function during replicative senescence. It has also examined the influence of RBPs in replicative senescence by interventions to elevate or reduce RBP levels, followed by the analysis of changes in senescence-associated mRNA expression patterns. We have studied if a given RBP binds a senescence-associated mRNA using a variety of in vitro binding assays (e.g., pulldown using biotinylated RNA segments and antisense oligomers) and assays to measure binding of endogenous molecules ribonucleoprotein immunoprecipitation (RIP) or crosslinking IP (CLIP). In recent years, we have included the analysis of noncoding RNAs microRNAs (mi)RNAs, long noncoding (lnc)RNAs, and circular (circ)RNAs that influence senescence and aging. Over the past 12 months, this Project has continued to examine changes in gene expression programs that occur in human tissues as part of physiologic aging. Much of our effort in this Project has been directed at understanding how proteins of different types (including RBPs), ncRNAs, and signaling pathways affect the process of cellular senescence, which is increasingly recognized as underlying age-related changes in tissue physiology and pathology. The studies in this Project examine the proteins and RNAs that modulate cellular senescence and the consequences of their influence on the senescent phenotype. Among the cell systems used for these studies, human diploid fibroblasts have been particularly informative, although we have expanded to over a dozen primary cells.

View original record on NIH RePORTER →