Systematic review of epigenetic age acceleration across neurological diseases
This systematic review of 79 adult human studies found epigenetic age acceleration often altered in neurological disease, but associations varied by clock, tissue and outcome; the abstract says current evidence does not support routine clinical use. [1]
Automatic summary · not editorially reviewed
The key findings
The review included adult human cohorts with neurological disease that applied methylation-based epigenetic clocks. [1]
Seventy-nine studies were included, and fifteen clocks were applied, most often Horvath, Hannum and PhenoAge. [1]
The authors state that current evidence does not support routine clinical use of EAA. [1]
The source at a glance
- Study type / format
- Systematic review (abstract)
- Population / context
- Adult human cohorts with neurological disease
- Summary based on
- Study abstract
- Original publication
- June 3, 2026
Review question on epigenetic clocks in neurological disease
The review asked how epigenetic age acceleration (EAA) appears across neurological diseases. EAA is the difference between methylation-based epigenetic age and chronological age. The authors describe it as a potential biomarker of ageing and disease mechanisms, reflecting cumulative genetic, environmental and disease-related influences. The review followed PRISMA guidelines and searched four databases from inception to October 2025. Eligible studies were adult human cohorts with neurological disease that applied methylation-based clocks and reported clinical, neuroimaging, neuropathological, prognostic or causal outcomes.
Supporting source [1]
79 studies, 15 clocks, heterogeneous associations
Seventy-nine studies covering multiple neurological conditions were included. Fifteen clocks were applied, most often Horvath, Hannum and PhenoAge. EAA was frequently altered in neurological disease, but associations varied by clock, tissue and outcome. Measures derived from the central nervous system showed more consistent relationships with neuropathological indices, whereas blood-based measures were more heterogeneous. Genetic and causal analyses provided limited and inconsistent evidence for direct causal effects. Because of heterogeneity, findings were synthesised narratively rather than pooled.
Supporting source [1]
Context-dependent interpretation, no routine clinical use
The authors conclude that EAA captures biological ageing signatures relevant to neurological disease, but that interpretation depends on context. They state that current evidence does not support routine clinical use. They suggest that improved standardisation and validation may clarify the role of epigenetic ageing in vulnerability to neurological disease. These are the conclusions reported in the abstract; the abstract does not report effect sizes or separate results for individual diseases.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. The abstract reports no effect sizes, no separate results per disease and no details of the individual studies. Findings were synthesised narratively because of heterogeneity, and genetic and causal evidence was limited and inconsistent.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Smith RD, Manavi D, Quigley N, Rafati Fard A, Toumbas G, McMurran CE, Kotter MR, Mowforth OD. · europepmc.org · June 3, 2026