Biological age acceleration is more prevalent in men than in women at time of spontaneous intracerebral hemorrhage
Objective:Spontaneous 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 individual's biological aging -it remains unknown whether this sex dimorphism also applies to ICH patients. Approach and Results: We 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). Conclusion:This study shows that biological age difference between women and men are not exclusive of ischemic stroke but also observed in ICH.