The Effect of Long-Duration Spaceflight on DNA Methylation of Longevity-Related Genes in a One-Year Astronaut Study

Abstract

The aging global population presents one of the most significant challenges of the 21st century, precipitating humanitarian, economic, and environmental burdens. Space provides a unique environment for studying longevity given the extreme hazards it poses to human health. Genomic damage and epigenetic changes have been observed in astronauts and animal models during spaceflight. Space agencies plan to launch long-duration missions (> 6 months) to the Moon and Mars within the next decade. The aim of this investigation is to interrogate the effects of a 340-day spaceflight mission on the methylation of genes associated with two hallmarks of aging, genomic instability and cellular senescence. This aim is based on the premise that spaceflight hazards like radiation induce the accumulation of epigenetic noise, and that epigenetic noise is both a feature and a driver of aging (Sinclair & LaPlante, 2019). The NASA Twins Study is the first year-long mission featuring genetically matched twin astronaut subjects and it provides a unique multidimensional molecular dataset for studying the effects of space on human aging (Garrett-Bakelman et al., 2019). In this investigation, longitudinal genome-wide methylation data obtained from the NASA Twins Study was intersected with a set of 30 longevity-related candidate genes to uncover differential DNA methylation and biological age estimates were obtained using computational tools. Analysis of mean differential methylation results across preflight, inflight, and postflight mission periods revealed negligible significant changes in DNA methylation of candidate genes in the space-bound twin and a number of significant changes in the earthbound twin. Analysis of biological age using an epigenetic clock algorithm revealed no significant change in rate of aging in the space-bound twin. The paradoxical results of this investigation raise novel questions about the role of DNA methylation as a marker of aging in space and underscore the need for additional longitudinal studies in larger groups of astronauts with longer postflight follow-up periods.