An updated landscape of cellular senescence heterogeneity: Mechanisms, technologies and senotherapies

Abstract

Chronic aging represents the leading risk factor for the vast majority of age-related diseases, which together contribute to increased morbidities and elevated mortalities in late life. Senescent cells are highly associated with organismal aging and pathological conditions, and can be selectively targeted to delay aging process. Recent studies have presented novel senescence markers beyond p16INK4a, a widely used molecular index, and have highlighted the importance of unraveling senescence heterogeneity among cell types, tissues and even species. Despite intense interest in search for robust and unique markers of senescence, the highly heterogeneous and dynamic nature of senescence-associated phenotypes has made this task a daunting challenge. However, recent development of high-throughput technologies, particularly single cell/nucleus RNA sequencing (sc/snRNA-seq), enables analysis of senescent cells at the single-cell level and supports potential discovery of new markers. In this article, we propose that there is an urgent need to investigate the mechanisms underlying senescence heterogeneity and discuss how this could be accomplished with the application of advanced technologies and sequencing datasets publicly available.

Keywords

• Aging
• Cellular senescence
• Heterogeneity
• High-throughput technology
• Single-cell
• Senotherapy