While we have always thought of stress as something that will send us an early grave, fascinating new findings now suggest that early life stress may actually prevent such a dreaded fate. New research from the stress-resilient team in the lab Ursula Jakob (University of Michigan, Ann Arbor, MI, USA) has now linked increased levels of stress during developmental stages in the nematode C. elegans to improved stress resistance and longevity thanks to an epigenetic effect.
The talented team knew of previous studies in their widely used model organism that linked individuals displaying increased oxidative stress (due to an elevation in reactive oxygen species (ROS) levels) to extended lifespan and increased stress resistance. Overall, this body of work suggested that, fascinatingly, this stressor may serve to modulate lifespan and early developmental stages.
So put your troubles to one side for five minutes, grab a mug of something hot and soothing, and let’s delve into this new stress-free study:
- Using a population of synchronized C. elegans that ubiquitously express an integrated redox-sensing protein, the authors established that the transient, seemingly random increases in ROS that occur naturally during early development increase stress resistance (to heat shock and the presence of oxidants) in adult animals and prolongs median lifespan by up to 18%
- However, subsequent gene expression analyses demonstrate a surprising lack of changes to common heat-shock- and oxidative stress-related genes in animals with higher ROS levels
- Instead, increases in ROS levels lead to a global decrease in H3K4me3 levels (as detected by Western blotting), which may mediate the phenotypic changes observed
- Around a quarter of those differentially expressed genes discovered in C. elegans with high ROS levels possess a developmentally set H3K4me3 modification, according to an analysis of published chromatin immunoprecipitation data
- Confirmatory studies in human cancer cells confirmed the ROS-sensitivity of global H3K4me3 levels and an increase in stress resistance following depletion of H3K4me3 levels via siRNA targeting of an H3K4 methylase complex member
- Additional in vitro studies identified the SET1/MLL histone methyltransferases as redox sensors of the COMPASS H3K4-trimethylase complex
- Mass spectrometry highlighted that ROS levels influence histone methylation activity by the oxidation of conserved cysteines in the SET domain, and this represents the first description of this type of regulation
Overall, these findings implicate a fascinating link between early-life events, ROS-sensitive epigenetic marks, stress resistance, and lifespan. Senior author Ursula Jakob shares, “The general idea that early life events have such profound, positive effects later in life is truly fascinating. Given the strong connection between stress, aging, and age-related diseases, it is possible that early events in life might also affect the predisposition for age-associated diseases, such as dementia and Alzheimer’s disease.”
So, it seems that at our age, there is no real point stressing out! So put that paper draft down, and lay back, relax, and delve into this chilled-out new study at Nature, December 2019.