What T -cell Acute Lymphoblastic Leukaemia and Senescing microglial CNS disease have in common relate to Notch and Glucocorticoid signaling. DJGPhD 07 December 2020

Aging  and chronic stress can obtain activation of CNS-resident microglia and astrocytes, that produce  type 1 interferons (T1 IFNs) which signal through the heterodimeric IFN-α/β receptor (IFNAR) where receptor binding of  T1 IFNs activates the JAK/STAT thus inducing  IFN-stimulated genes (ISGs) which mediate both pro- and anti-inflammatory functions depending upon the cellular micro-environment.

Now consider how aging is linked to elevated & activated leukocyte counts and it becomes clear that this is a patho-biochemical phenocopy to T cell acute lymphoblastc leukaemia  (T-ALL) where signaling through Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK are shared.

IL7-induced glucocorticoid resistance is diagnostic of certain subtypes of T-ALL and this is also associated with the senescence associated secretory phenotype of aging-linked morbidity and mortality.

Finally, consider that chronic CNS stress leads to increased  glucocorticoid production leading to  a suppression of cell adhesion protein thus corrupting synaptic plasticity, memory re-formation, and cognitive acuity while promoting sarcopenia  by stimulating proteasomal removal of contractile proteins and inhibiting the  PI3-kinase/Akt pathway. Glucocorticoids also prevent IL-2 synthesis and secretion  thus causing immune suppression by blocking T cell activation.

J Neuroinflammation. 2019; 16: 236.

Cytokine & Growth Factor Reviews, 22 Apr 2017, 35:85-96

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