. 2020 Jun 9;12:168. doi: 10.3389/fnagi.2020.00168

TABLE 1.

Observed changes in senescent cells and in Tat-exposed cells.

Senescence-induced changes	Tat-induced changes	References
Senescent cells have disorganized and diffuse TJP expression and increased BBB permeability	Tat exposure in astrocytes results in increased MMP-9 and cleaved occludin. BMECs exposed to Tat have decreased occludin and claudin-5 TJP mRNA	Johnston et al., 2001^T; Andras et al., 2005^T; Eugenin et al., 2011^T; Rao et al., 2014^T; Atluri et al., 2015^T; Yamazaki et al., 2016^S
Senescent cells secrete pro-inflammatory cytokines including Increased secretion of IL-6, CCL5, IL-8, MMP-1	BMECs exposed to Tat secrete IL-6 and TNF-α. Tat activates transcription factors like Sp1 and NF-κB to increase production of pro-inflammatory cytokines TNF-α, CCL2, IL-2, IL-6, CCL5, and IL-8. Neurons exposed to Tat produce TNF-α, and IL-1β	Liu et al., 2011^S; Rao et al., 2014^T; Dickens et al., 2017^B; Baker and Petersen, 2018^S; Cohen et al., 2018^S; Herranz and Gil, 2018^S; Hijmans et al., 2018^S; Ajasin and Eugenin, 2020^T
Increased expression of ICAM-1	Tat alters the expression of adhesion molecules such as ZO-1, JAM-A, PECAM-1 and CD99	Bhat et al., 2012^S; Baker and Petersen, 2018^S; Ajasin and Eugenin, 2020^T
Increased oxidative stress (including ROS and NO production)	Tat exposure can increase oxidative stress (can increase ROS and NO production by causing ER stress)	Capone et al., 2013^T; Baker and Petersen, 2018^S; Jeon et al., 2018^S
Increased expression of p16 and p21	Tat exposure on MSCs resulted in increased p21 expression	Liu et al., 2011^S; Bhat et al., 2012^S; Beaupere et al., 2015^S,T; Baker and Petersen, 2018^S; Cohen et al., 2018^S
A feature of senescence is the permanent exit and the cell cycle and block in cell growth	Tat exposure reduced population doubling in MSCs, and reduced cell growth in U373. MG cells, primary mouse astrocytes and 293T cells	Zhou et al., 2004^T; Beaupere et al., 2015^S,T; Childs et al., 2018^S; Langford et al., 2018^T

^S, references for senescence-induced changes; ^T, references for Tat induced changes.