TABLE 2.

Biomarkers of cellular senescence and their respective functions.

Senescent trait	Biomarkers	Functional implications	Relevance in vascular senescence	References
Cell-cycle arrest	p53/p21CIP1	Inhibition of cell-cycle	OIS, DDR-induced senescence, ROS-induced senescence, replicative senescence	Chen (2016)
		The onset of cellular senescence
	p16INK4A/pRB	Inhibition of cell-cycle	ROS-induced senescence, OIS, and replicative senescence	Grosse et al. (2020)
		Maintenance of cellular senescence
	p38/CDKIs p15 and p27	Mitogenic activity	Role not clearly defined	Russo et al. (2020)
Metabolic dysregulation	SA-β-Gal	Lysosomal protein activity in senescent cells	Hydrolytic enzyme implication in β-galactosidase conversion to monosaccharide Evidence of increased lysosomal mass	Debacq-Chainiaux et al. (2009)
Macromolecular damage	Lipids of membrane	Altered levels	Increase in EPA, 7-HOCA, malonate, and 1-stearoylglycerophosphoinositol	James et al. (2015)
			Decrease in dihomo-linoleate, linoleate, and 10-heptadecenoate
	Lipofuscin	Accumulation in senescent cells	Emerging as a hallmark of senescence. Role not clearly defined	Georgakopoulou et al. (2013), Evangelou and Gorgoulis (2017), Brickute et al. (2022)
	ROS	Cellular damage	ROS-induced senescence	Korovila et al. (2017)
	Telomeres	Telomere shortening	Replicative-induced senescence
	Lamin B1	Loss of lamin B1	Disruption of the nuclear membrane and induction of senescence	Freund et al. (2012)
Epigenetic regulation	CpG Sites	Accumulation associated with histone variant H3.3	Links to DNA methylation alterations and chromatin accessibility	Cheng et al. (2017)
	Histone modifications	Gene expression regulation	Influences SASP, proliferation arrest, and gene enhancer activation	Salama et al. (2014)
	L1 retrotransposons	Activates cGAS-STING pathway	Induces type 1 interferon response, genomic instability, and SASP	Criscione et al. (2016)
	miRNAs	Targeted actions on various genes/proteins	Implicated in diverse vascular functions and pathogenic mechanisms	Menghini et al. (2014), Nikolajevic et al. (2022)
	AGO2	Complex formation with RB1	Facilitates CD2 and CDCA8 expression	Benhamed et al. (2012)
Inflammation (SASP)	IL-6	Implicated in hypertension	Strong correlation with hypertension; Lowered by angiotensin II-receptor blockade therapy	Passacquale et al. (2016), Stevenson et al. (2018)
	C-reactive protein	Triggered by inflammatory mediators	Aging risk factors and Inflammatory biomarker	Tang et al. (2017)
	GDF-15	Secreted by senescent endothelial cells	Impacts angiogenesis, apoptosis, and inflammation	Ha et al. (2019)