Community-living nonagenarians in Northern Ireland have lower plasma homocysteine but similar methylenetetrahydrofolate reductase thermolabile genotype prevalence compared to 70–89-year-old subjects

This cross-sectional study assessed relationships between plasma homocysteine, ‘thermolabile’ methylenetetrahydrofolatereductase (MTHFR) genotype, B vitamin status and measures of renal function in elderly (70–89 years) and nonagenarian (90+ years) subjects, with the hypothesis that octo/nonagenarian subjects who remain healthy into old age as defined by ‘Senieur’ status might show reduced genetic or environmental risk factors usually associated with hyperhomocysteinaemia. Plasma homocysteine was 9.1 μmol/l (geometric mean [GM]) for all elderly subjects. Intriguingly, homocysteine was significantly lower in 90+ (GM; 8.2 μmol/l) compared to 70–89-year-old subjects (GM; 9.8 μmol/l) despite significantly lower glomerular filtration rate (GFR) and serum B12 in nonagenarian subjects and comparable MTHFR thermolabile (TT) genotype frequency, folate and B6 status to 70–89-year-olds. For all elderly subjects, the odds ratio and 95% confidence intervals for plasma homocysteine being in the highest versus lowest quartile was 4.27 (2.04–8.92) for age <90 compared >90 years, 3.4 (1.5–7.8) for serum folate <10.7 compared >10.7nmol/l, 3.0 (0.9–10.2) for creatinine >140 compared <140 umol/l and 2.1 (1.0–4.4) for male sex. This study shows that plasma homocysteine does not invariably increase with age. Compared to similarly enlisted 70–89-year-olds, apparently well, mentally alert, community-living 90+ year olds approximating ‘Senieur’ status, show lower homocysteine, which is unexplained by renal function, TT genotype and B vitamin status, suggesting that lower homocysteine may be associated with survival.