The heterogeneity of cellular senescence: insights at the single-cell level

Abstract

Senescent cells are highly associated with aging and pathological conditions and could be targeted to slow the aging process. One commonly used marker to examine senescent cells in vivo is p16, which has led to important discoveries. Recent studies have also described new senescence markers beyond p16 and have highlighted the importance of investigating senescence heterogeneity in cell types and tissues. With the development of high-throughput technologies, such as single-cell RNA-seq and single-nucleus RNA-seq, we can examine senescent cells at the single-cell level and potentially uncover new markers. This review emphasizes that there is an urgent need to investigate senescence heterogeneity and discuss how this could be accomplished by using advanced technologies and sequencing datasets.

Keywords: RNA-sequencing; aging; p16; p21; senolytics.

Figure 1.. A summary of the current consensus on the biology of senescent cells.

Senescent cells accumulate in tissues with aging and disease, and with various physiological conditions. They are in a state of proliferative arrest and use senescent cell antiapoptotic pathways to maintain their prosurvival networks. They have the senescence-associated secretory phenotype (SASP) that can damage the surrounding tissue and have increased expression of the cyclin-dependent kinase inhibitors p16 and p21 and decreased expression of lamin B1. Senescent cells also exhibit increased granularity, cytosolic DNA, senescence-associated-β-galactosidase (SA-β-gal) staining, telomere shortening, telomere-associated foci (TAF), and senescence-associated heterochromatin foci.