Review Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Physical Fatigue Through the Perspective of Immunosenescence 2025 Ke et al

[Andy]

ABSTRACT​

Background​

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness marked by persistent fatigue, yet its mechanisms remain unclear. Growing evidence implicates immunosenescence—the age-related decline in immune function—in the onset and persistence of fatigue.

Methods​

This review synthesizes clinical and experimental data to examine how immunosenescence contributes to ME/CFS. We focus on chronic inflammation, senescent immune phenotypes, mitochondrial dysfunction, and neuroendocrine imbalance, with emphasis on maladaptive crosstalk among immune, muscular, neuroendocrine, and vascular systems.

Results​

Aging immune cells drive chronic inflammation that impairs mitochondrial ATP production and promotes muscle catabolism. Concurrently, HPA-axis suppression and β2-adrenergic dysfunction amplify immune dysregulation and energy imbalance. Together, these processes illustrate how immunosenescence sustains pathological cross-organ signaling underlying systemic fatigue.

Conclusion​

Immunosenescence provides a unifying framework linking immune, metabolic, and neuroendocrine dysfunction in ME/CFS. Recognizing cross-organ communication highlights its clinical relevance, suggesting biomarkers such as cytokines and exhaustion markers, and supports integrated therapeutic strategies targeting immune and metabolic networks.

Paywall

 

[Creekside]

Are they claiming that this immunosenescence also occurs in young people? Does immunosenescense abruptly switch off and then back on again? To me it looks like a theory that seems okay only if you limit which cases of ME you study.

 

[Utsikt]

I wonder how this could possibly fit with the early age peak that some have observed? And I don’t think there’s any data to indicate that the risk of developing ME/CFS increases with age?