Biological age acceleration is more prevalent in men than in women at time of spontaneous intracerebral hemorrhage

ObjectiveSpontaneous intracerebral hemorrhage (ICH) occurs later in life in women compared to men. Although previous studies have demonstrated epigenetic age acceleration (EAA) differences in ischemic stroke (IS) patients - a measure of an individuals biological aging -it remains unknown whether this sex dimorphism also applies to ICH patients. Approach and ResultsWe joined two ICH cohorts (N= 200, 45% women: 76.8{+/-}13 years; 55% men: 67.9{+/-}14 years). DNAm levels were obtained from whole blood samples using Illumina EPIC array. We evaluated three age-predictor clocks (Horvath, Hannum and Zang-BLUP) and one health-status clock (Levine) and their respective EAA metrics including extrinsic EAA (EEAA) and intrinsic EAA (IEAA) measures. We compared aging measures between women and men, then performed an ICH-subtype stratification, a specificity analysis evaluating sex differences in non-stroke samples (N= 350, 54% women 60.8{+/-}8 years, men: 60.8{+/-}10 years) and replication of previous result in a new IS cohort (N= 657, 43% women 73.6{+/-}12 years, men: 70.1{+/-}11 years). Women at time of ICH present lower EAA values than men (Horvath-EAA, p-value=1x10-04; Hannum-EAA, p-value=8.1x10-06; BLUP-EAA, p-value=4.4x10-04) as well as lower extrinsic EAA values (Horvath-IEAA, p-value=3.1x10-03; Hannum-IEAA, p-value=6.5x10-04). These differences seemed to be driven by differences in deep-ICH patients. Non-ICH females have lower acceleration values (Hannum-EAA: -10,37) than non-ICH men (Hannum-EAA: -8,01), but the differences are smaller than in ICH cases (ICH-women Hannum-EAA: -9,26, ICH-men Hannum-EAA: -2,6). This pattern was consistent in the IS cohort, where women were chronologically older than men but had similar biological age and significantly lower epigenetic age acceleration across multiple measures (Horvath-EAA, p = 2.6x10-3; Hannum-EAA, p = 7.1x10-3; Horvath-IEAA, p = 1.6x10-2; Hannum-IEAA, p = 4.5x10-2). ConclusionThis study shows that biological age difference between women and men are not exclusive of ischemic stroke but also observed in ICH.