Schizophrenia has been proposed to be a disorder of accelerated ageing, characterised by a mismatch between biological and chronological age. Evidence accumulated over the past 15 years has examined this model using molecular, neuroimaging, cognitive and epidemiological markers.

To evaluate whether schizophrenia shows evidence of an accelerated or advanced ageing phenotype across biological systems and to assess the consistency of the underlying molecular mechanisms.

A systematic review (PROSPERO CRD42024574059) was conducted following PRISMA guidelines. PubMed and Google Scholar were searched for studies published after 2009 that cited the original accelerated ageing hypothesis publication or investigated ageing in the context of schizophrenia and/or psychosis. Evidence was synthesised narratively by domain, with emphases on meta-analyses and minimally treated, longitudinal cohorts.

A total of 923 manuscripts were identified, and a final 170 were included in the systematic review. Schizophrenia showed a reproducible ageing phenotype, as evidenced by in increased mortality, higher dementia risk, brain-predicted age elevation and cognitive decline. BrainAGE studies revealed mean age gaps of 3–4 years, often present at first episode. At the mechanistic level, meta-analyses reported consistent telomere shortening (standardised mean difference approximately –0.4 to –0.5) and modest acceleration of selected epigenetic clocks. Dysregulation of oxidative stress, inflammation, mitochondrial function and insulin-like growth factor-1 signalling were frequent and partly preceded antipsychotic exposure.

Schizophrenia is associated with a multisystem ageing phenotype underpinned by convergent biological mechanisms, most consistently involving telomere attrition and oxidative and/or inflammatory stress. The overall pattern supports a model of advanced rather than uniformly accelerated ageing, reflecting early biological deviation with parallel rather than steeper decline.

Few studies have quantitatively characterised the shared and distinct features of the epigenetic age signature of schizophrenia, bipolar disorder and major depressive disorder.

To construct a multi-platform epigenetic clock tailored to human blood and brain tissues, and to characterise variations in epigenetic age acceleration across these three common psychiatric disorders.

We integrated 31 publicly available DNA methylation data-sets generated on the platforms Illumina 27K, 450K and EPIC (850K) from patients with schizophrenia, bipolar disorder or major depressive disorder, and from matched controls. Using elastic net regression combined with sure independence screening, we developed the blood–brain clock and applied it to assess disorder-specific epigenetic age acceleration in blood and brain.

The blood–brain clock achieved high accuracy across tissues and outperformed established predictors, particularly in brain samples. Epigenetic age acceleration was reduced in schizophrenia, increased in bipolar disorder and major depressive disorder and strongly elevated in Alzheimer’s disease (positive control). Alterations appeared earlier in blood than in brain. Meta-analysis confirmed that both reduced acceleration (schizophrenia) and increased acceleration (bipolar disorder, major depressive disorder, Alzheimer’s disease) were significantly associated with disease prevalence. Differential methylation analyses further revealed that the blood–brain clock probes captured disease-associated signals, with schizophrenia showing the greatest overlap with causal risk loci, and opposite methylation patterns distinguishing schizophrenia from bipolar disorder or major depressive disorder. A subset of blood DNA methylation probes enabled high-precision classification between schizophrenia and bipolar disorder or major depressive disorder.

This blood–brain clock reveals distinct patterns of epigenetic age acceleration across psychiatric disorders, reflecting disorder-specific and shared biological ageing signatures. The manifestation of these alterations in peripheral blood highlights its potential as a non-invasive biomarker for early detection, risk stratification and differential classification of schizophrenia, bipolar disorder and major depressive disorder.

The current study examined if early adversity was associated with accelerated biological aging, and if effects were mediated by the timing of puberty.

In early mid-life, 187 Black and 198 White (Mage = 39.4, s.d.age = 1.2) women reported on early abuse and age at first menstruation (menarche). Women provided saliva and blood to assess epigenetic aging, telomere length, and C-reactive protein. Using structural equation modeling, we created a latent variable of biological aging using epigenetic aging, telomere length, and C-reactive protein as indicators, and a latent variable of early abuse using indicators of abuse/threat events before age 13, physical abuse, and sexual abuse. We estimated the indirect effects of early abuse and of race on accelerated aging through age at menarche. Race was used as a proxy for adversity in the form of systemic racism.

There was an indirect effect of early adversity on accelerated aging through age at menarche (b = 0.19, 95% CI 0.03–0.44), in that women who experienced more adversity were younger at menarche, which was associated with greater accelerated aging. There was also an indirect effect of race on accelerated aging through age at menarche (b = 0.25, 95% CI 0.04–0.52), in that Black women were younger at menarche, which led to greater accelerated aging.

Early abuse and being Black in the USA may both induce a phenotype of accelerated aging. Early adversity may begin to accelerate aging during childhood, in the form of early pubertal timing.