Aging-associated SASP vs. MiDAS is a contrarion trade-off that may lead to neurodegeneration and autoinflammation vs tumorigenesis and heart disease respectively. Dr. Dan Guerra.17 Jan 2021. AB

The anti-inflammatory IL-10 pathway in the CNS can lead to Glioblastoma which is a disease presented 3-4 fold higher in people ≥65 years old, and with a mortality rate for the same age group some 7 fold higher. Activation of the IL-10 Receptor bound ligand induces the JAK1 signal transducer and activator of transcription 3 (STAT3) pathway in APCs. This results in the subsequent translocation of STAT3 homodimers into the nucleus. This STAT3 homodimer binds to STAT-binding elements which promotes the expression of the suppressor of cytokine signaling 3 (SOCS-3) and IL-1 receptor antagonist (IL-1RN).  IL-10 reduces the production of pro-inflammatory cytokines (IL-1β, IL-6, tumor necrosis factor alpha) and diminished expression of both major histocompatibility complex II.

The anti-inflammatory  MiDAS phenotype can also induce heart failure in the aging population.

References:

Front Pharmacol. 2019; 10: 200

Aging Cell. 2018 Oct;17(5)

Int Heart J. 2018 Jul 31;59(4):837-844

Front. Immunol., 19 March 2018

Neuro Oncol . 2020 Mar 5;22(3):333-344