High-Throughput CRISPR Screening for Aging Regulators: focusing on functional genomic screens to identify targets that drive or protect against senescence

Aging research increasingly focuses on unraveling the genetic and molecular mechanisms that drive cellular senescence and tissue decline. Although transcriptomic and proteomic studies have identified numerous candidate genes associated with the aging process, distinguishing between causal regulators and correlative markers remains a major scientific challenge. The rise of high-throughput CRISPR screening - both pooled and arrayed - has transformed functional genomics by enabling systematic and scalable genome-wide interrogation of gene function in diverse biological contexts. When coupled with phenotypic readouts, selective pressures, or single-cell sequencing approaches such as Perturb-seq, these screens offer unprecedented resolution to map the regulatory networks that determine cellular lifespan and resilience to stress. Recent findings reveal that CRISPR-based tools can uncover novel genetic determinants of senescence, rejuvenation, and organismal longevity, but large-scale integration across models and systems is still limited.This Research Topic aims to accelerate progress at the intersection of genome editing and aging research by showcasing efforts to identify functional targets that drive or protect against senescence. It seeks to bring together studies employing CRISPR-based loss- and gain-of-function methodologies - including CRISPRko, CRISPRa, CRISPRi, and prime or base editing - to uncover therapeutic mechanisms underlying aging regulation. Central questions include: Which molecular pathways represent nodes of vulnerability in aging cells? How can CRISPR genome-wide screens be designed to distinguish pro-aging from protective factors? And which identified genes hold translational potential for novel senotherapeutic interventions?To gather further insights in the area of functional genomic dissection of aging, we welcome articles addressing, but not limited to, the following themes:- Genome-wide CRISPR screens (knockout, activation, and interference) designed to identify positive and negative regulators of cellular senescence, replicative exhaustion, or stress-induced premature senescence (SIPS).- Single-cell functional genomics (e.g., Perturb-seq, CROP-seq) mapping the transcriptional and epigenetic landscapes of aging and senescence at single-cell resolution.- In vivo and 3D organoid CRISPR screening methodologies to identify tissue-specific senescence regulators and microenvironment-dependent aging mechanisms.- Epigenetic CRISPR screening (CRISPRi/a) focused on histone modifications, DNA methylation, and chromatin remodeling factors that dictate the senescent program.- Screening for non-coding regulatory elements, including lncRNAs, miRNAs, and enhancers, that modulate longevity pathways and cellular quality control.- Translational and therapeutic pipeline discovery based on CRISPR screens to identify druggable targets and synthetic lethal vulnerabilities in senescent cells.- Computational and machine learning approaches for processing and modeling high-throughput CRISPR screening data in aging network analyses. Topic editors: Yongpan An, Zhao Ding Source: https://www.frontiersin.org/research-topics/83733/high-throughput-crispr-screening-for-aging-regulators-focusing-on-functional-genomic-screens-to-identify-targets-that-drive-or-protect-against-senescence