Work

Mosaic loss of Y chromosome and the association to mortality in Danish men aged 56–100 years

Year: 2024

Type: article

Abstract: Mosaic loss of the Y chromosome (mLOY) is a common somatic mutation in the blood of elderly men and several studies have found mLOY in blood cells to be associated with an increased risk of various diseases and mortality. However, most of these studies have focused on middle-aged and older adults, meaning that mLOY in extremely old individuals like centenarians is understudied. To explore mLOY across a wider age range compared to earlier studies and to specifically focus on centenarians, mLOY was estimated in 917 Danish men aged 56–100 years. We found that the percentage of men with LOY increased with age until age 85, after which it plateaued at around 40 %. Consistently, a longitudinal comparison of mLOY revealed that mLOY predominantly increased with age, although inter-individual variation was seen. Using a twin sub-sample, the broad-sense heritability of mLOY was estimated at 72 %, indicating a substantial genetic influence. Supporting previous findings, mLOY was found to associate with increased mortality across all study participants and in men younger than 80 years. In centenarians, however, a higher level of mLOY associated with better survival, most likely due to selection, although confirmation of our findings in larger studies is needed. • The proportion of men with mLOY increases until age 85 years and then plateaus. • mLOY increases with age, although with substantial inter-personal variation. • The broad-sense heritability of mLOY in Danish 70+ year-old men is 72 %. • mLOY associated with mortality in all study participants and in men below 80 years. • mLOY associated with better survival in centenarians, likely due to selection.

Source: Mechanisms of Ageing and Development

DOI: 10.1016/j.mad.2024.111979