Review of evidence linking exposure to environmental stressors and associated alterations in the dynamics of immunosenescence (ISC) with the global increase in multiple sclerosis (MS)

Table 2 The occurrence of immune cell-related features of arISC following exposure to environmental stressors and during MS

Feature	Reference	Environmental stressor	Reference	MS	Reference
Morphological changes^*	[277]	V	[252]	NV
Telomere attrition	[278]	V	[124, 279]	V	[231, 239, 242, 243]
Restricted ribonuclease telomerase	[278]	V	[280]	NV
SASP activation^*	[285]	V	[286]	V	[222, 229]
Downregulated CD27†	[281, 282]	NV		V	[283]
Downregulated CD28	[278, 284]	NV		V	[283]
Upregulated CD45RA/TEMRA	[216, 219]	NV		V	[283, 289, 290]
Upregulated CD57	[216, 284, 287]	NV		V	[288]
Upregulated TIM-3	[216]	NV		V	[211]
Upregulated KLRG-1	[219, 284]	NV		NV
Reduced perforin/granzyme B	[219]	NV		V	[298]
Increased p16^INK4a	[291, 292]	V	[108, 252]	V	[297]
Increased p21 CIP1/WAF1/SD11	[293, 294]	V	[252]	NV
Increased p53	[295, 296]	V	[252]	V	[299]
Activated p53-p21 pathway^*	[249]	V	[252]	V	[272]
SA-β-gal^*	[223]	NV		NV
DNA damage	[255]	NV		NV
Lipofuscin	[300]	V	[301, 302]	NV

There is no single biomarker with absolute specificity for cellular or immune cell senescence [188] and a multi-marker approach to detection and identification, in non-MS and MS-based studies, has been applied in the compilation of Tables 1 and 2. Furthermore, the biomarkers, some of which are, to date, not verified (NV) or verified (V) and common to pISC and arISC (*) following exposure to environmental stressors or during MS, and confirmed in immune cell populations as previously detailed [309,310,311]. Verification of MS-associated or environmental risk factor-related hallmarks of immune cell-related senescence indicates a close inter-relationship. There is also an inter-connection provided by the comprehensive picture of a relationship with pISC and arISC despite conjecture over biomarker expression in MS (†) [312,313,314,315,316,317]

ISSN: 1742-4933