Tag: unifying theory

DNA methylation: unifying framework for complex chronic conditions

Abstract:

Complex chronic conditions represent a growing health burden that is poorly understood and inadequately managed within current health systems. This review focuses on the potential of epigenetic DNA methylation to provide a pathway for better understanding of four closely related conditions: myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), long COVID (LC), fibromyalgia (FM), and hypermobile Ehlers-Danlos syndrome (hEDS).

These conditions have extensive overlapping symptoms, suggesting shared underlying pathophysiological mechanisms. Epigenetic regulation, particularly DNA methylation, provides a powerful framework for comparative and longitudinal studies across these clinically overlapping conditions.

Here, we synthesise evidence from current DNA methylation studies in ME/CFS, LC, and FM, and consider how an integrated cross-condition approach could advance mechanistic insight, enable diagnostic stratification, and improve patient outcomes.

Source: Sharma S, Rodger EJ, Chatterjee A, Tate WP. DNA methylation: unifying framework for complex chronic conditions. Trends Genet. 2026 Sep 24:S0168-9525(26)00221-0. doi: 10.1016/j.tig.2026.09.001. Epub ahead of print. PMID: 42786072. https://www.cell.com/trends/genetics/fulltext/S0168-9525(26)00221-0 (Full text)

mTORC1 syndrome (TorS): unifying paradigm for PASC, ME/CFS and PAIS

Abstract:

Post-acute SarS-Cov2 (PASC), Myalgia encephalomyelitis/Chronic fatigue syndrome (ME/CFS) and Post-acute infection syndrome (PAIS) consist of chronic post-acute infectious syndromes, sharing exhaustive fatigue, post exertional malaise, intermittent pain, postural tachycardia and neuro-cognitive-psychiatric dysfunction. However, the concerned shared pathophysiology is still unresolved in terms of upstream drivers and transducers. Also, risk factors which may determine vulnerability/progression to the chronic phase still remain to be defined.

In lack of drivers and a cohesive pathophysiology, the concerned syndromes still remain unmet therapeutic needs. ‘mTORC1 Syndrome’ (TorS) implies an exhaustive disease entity driven by sustained hyper-activation of the mammalian target of rapamycin C1 (mTORC1), and resulting in a variety of disease aspects of the Metabolic Syndrome (MetS), non-alcoholic fatty liver disease, chronic obstructive pulmonary disease, some cancers, neurodegeneration and other [Bar-Tana in Trends Endocrinol Metab 34:135-145, 2023]. TorS may offer a cohesive insight of PASC, ME/CFS and PAIS drivers, pathophysiology, vulnerability and treatment options.

Source: Bar-Tana J. mTORC1 syndrome (TorS): unifying paradigm for PASC, ME/CFS and PAIS. J Transl Med. 2025 Mar 10;23(1):297. doi: 10.1186/s12967-025-06220-z. PMID: 40059164. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06220-z (Full text)