The influence of epigenetic biological age on key complications and outcomes in aneurysmal subarachnoid haemorrhage

J Neurol Neurosurg Psychiatry. 2024 Jun 17;95(7):675-681. doi: 10.1136/jnnp-2023-332889.

Abstract

Background: We aimed to investigate the association between DNA-methylation biological age (B-age) calculated as age acceleration (ageAcc) and key aneurysmal subarachnoid haemorrhage (aSAH) complications such as vasospasm, delayed cerebral ischaemia (DCI), poor outcome, and mortality.

Methods: We conducted a prospective study involving 277 patients with aSAH. B-age was determined in whole blood samples using five epigenetic clocks: Hannum's, Horvath's, Levine's and both versions of Zhang's clocks. Age acceleration was calculated as the residual obtained from regressing out the effect of C-age on the mismatch between C-age and B-age. We then tested the association between ageAcc and vasospasm, DCI and 12-month poor outcome (mRS 3-5) and mortality using linear regression models adjusted for confounders.

Results: Average C-age was 55.0 years, with 66.8% being female. Vasospasm occurred in 143 cases (51.6%), DCI in 70 (25.3%) and poor outcomes in 99 (35.7%), with a mortality rate of 20.6%. Lower ageAcc was linked to vasospasm in Horvath's and Levine's clocks, whereas increased ageAcc was associated with 12-month mortality in Hannum's clock. No significant differences in ageAcc were found for DCI or poor outcome at 12 months with other clocks.

Conclusions: Our study indicates that B-age is independently associated with vasospasm and 12-month mortality in patients with aSAH. These findings underscore the potential role of epigenetics in understanding the pathophysiology of aSAH-related complications and outcomes.

Keywords: CEREBROVASCULAR DISEASE; GENETICS; SUBARACHNOID HAEMORRHAGE.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Brain Ischemia* / genetics
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Subarachnoid Hemorrhage* / complications
  • Subarachnoid Hemorrhage* / genetics
  • Vasospasm, Intracranial* / etiology
  • Vasospasm, Intracranial* / genetics