Aging drives a program of DNA methylation decay in plant organs.

Plants display a wide range of life spans and aging rates. Although dynamic changes to DNA methylation are a hallmark of aging in mammals, it is unclear whether similar molecular signatures reflect rates of aging and organism life span in plants. In this work, we show that the short-lived model plant Arabidopsis thaliana exhibits a loss of epigenetic integrity during aging, which causes DNA methylation decay and the expression of transposable elements. We show that the rate of epigenetic aging can be manipulated by extending or curtailing life span and that shoot apical meristems are protected from these epigenetic changes. We demonstrate that a program of transcriptional repression suppresses DNA methylation maintenance pathways during aging and that mutants of this program display a complete absence of epigenetic decay while physical aging remains unaffected. Editor's summary: DNA methylation typically represses the expression of transposable elements. Studying this process in a short-lived plant, Dai et al. found that epigenetic silencing of transposable elements declined as organs aged. However, this epigenetic aging did not occur in the self-renewing stem cell pools of shoot apical meristems, thereby resetting the aging clock in newly formed organs. Epigenetic organ aging did not occur when two transcription factors, TCX5 and TCX6, were absent, consistent with their roles in repressing DNA methylation. This study provides insight into how plants maintain different epigenetic states in different tissues according to their age and function. —Madeleine Seale INTRODUCTION: DNA methylation is a dynamic epigenetic modification to the genome of diverse eukaryotes, including plants, animals, and fungi. In mammals and humans, DNA methylation has emerged as a leading biomarker for biological age, yet the molecular mechanisms that contribute to these changes remain poorly understood. Plants share many similarities with mammals in their DNA methylation patterning, but the relationship between aging and epigenetic dynamics in plants is poorly understood. RATIONALE: Owing to the limitations of mammalian model species and cell culture systems, the dissection of molecular mechanisms underpinning epigenetic aging dynamics is challenging. We therefore sought to examine whether the short-lived and experimentally tractable model plant species Arabidopsis thaliana exhibits epigenetic aging dynamics comparable to those of mammals. The distinctive properties of plant growth and development also enabled us to address a number of key questions, including whether the age of individual organs can be decoupled from the age of the organism and how environmentally induced changes to life span affect epigenetic aging rates. RESULTS: We found that the leaves of A. thaliana exhibit DNA methylation decay during aging, which results in methylation losses in normally silenced genomic regions and the expression of transposable elements (TEs). By growing plants in short-day (8 hours light/16 hours dark) conditions, which extend life span about threefold, we demonstrate that the rate of DNA methylation decay is substantially reduced in longer-lived plants. Consistently, rates of DNA methylation decay are also faster or slower in natural or mutant genetic backgrounds with truncated or extended life spans, respectively. Additionally, we leveraged the flexible development of plants to show that newly emerged organs from older plants exhibited a youthful epigenetic state, thus demonstrating that the epigenetic ages of organs and organisms are decoupled. Finally, we described transcriptional repressors that inactivate DNA methylation maintenance genes during aging, thus driving age-related epigenetic changes. Mutants of these transcriptional repressors exhibited no DNA methylation decay during aging, despite their physical aging appearing to be mostly unaffected. CONCLUSION: The loss of DNA methylation at TEs and repetitive DNA during aging appears to be conserved across mammals and plants, despite their markedly different physical aging processes. These epigenetic dynamics appear to reflect an underlying biological age in plants, which echoes the properties of epigenetic aging clocks that have been established in humans and other mammals. The discovery of a mutant with a broken epigenetic aging clock suggests that age-related DNA methylation changes may be the consequence of programs that regulate the expression of DNA methylation maintenance factors in aging tissues. Our results also suggest that in plants, DNA methylation decay is unlikely to be a major causal factor behind physical aging. Epigenetic aging dynamics in plants.: TE sequences lose DNA methylation during aging in leaves, resulting in transcriptional activation. Epigenetic aging is driven by TCX5 and TCX6, which repress DNA methylation maintenance genes during aging. Shoot apical meristems (SAMs) are protected from epigenetic aging dynamics. WT, wild-type. [ABSTRACT FROM AUTHOR]