I see @sharansurya.bsky.social, who contributed to this project with repeated generational elevated glucose exposure experiments, is now on bluesky!

...of starvation actually extends organismal lifespan. If hypoxia is too dramatic that would obviously cause death, but if you have a sufficient exposure to induce the stress response pathways it can be beneficial! In this case the worms sacrifice fertility and shunt nutrients towards living longer

Thanks a lot! I know it's a bit counter-intuitive, but often times exposure to low levels of stress can induce the stress response pathways and then organisms have a beneficial response (termed hormesis). It's a similar theory to how dietary restriction, a reduction of food but not to the point ..

to a changing enivornment. I think we've evolved such that stresses that are strong enough are then transmitted to the descendants to alert them that conditions are not ideal and they should prepare for the adverse environment. But they are plastic so the hope is that adverse ones can be overcome

In plants I'm unfortunately not as familiar with the literature but again I'd be surprised if a sudden loss of nutrients or sunlight wouldn't have some consequence if it went on for long enough. Epigenetics exists right at the interface between the environment and genetics so it allows us to adapt

Thanks very much! Yes I think that even a "brief" stress if dramatic enough can have transgenerational consequences. The best examples in people are with the Överkalix study but I'd be surprised if dramatic overfeeding and starvation events didn't have a transgenerational consequence.

Thanks very much Dana!

Thanks so much!

Thanks a lot Oded! Been a fun project to work on for sure

Thanks a lot Amy! It's been a super fun project for sure!

Thanks! It's been a fun project for sure!

This exciting story was spearheaded by Kathleen but she was helped by a number of people mostly not on bluesky including Ariel Telger, Gautam Sarkar, Sharan Surya, Hafiz Rothi, @mpmeers.bsky.social, and Simon Yuan Wang. 9/9

Really excited for the next steps of this project to further study whether transgenerational adaptation is universal to different environmental stresses, how conserved this is in other species, and what the precise molecular mechanism is for the transgenerational adaptation. 8/9

We also performed a directed screen and identified that depletion of the argonautes CSR-1 and HRDE-1 accelerated the transgenerational adaptation (2 generations instead of 4 for no fertility phenotype) and depletion of the H3K27 trimethylase PRC2 complex eliminated the worms ability to adapt 7/9

..is not unique to hypoxia and might be a general phenomena. We performed RNAseq to examine which genes were adapting their expression to repeated generational hypoxia exposure. We found that most genes still respond to hypoxia treatment but a small subset adapt to repeated generational hypoxia 6/9

We also tested elevated glucose which increases neutral lipids and decreases fertility in exposed worms and unexposed descendants. After two successive exposures to elevated glucose neutral lipid levels and fertility were the same as unexposed controls.Therefore transgenerational adaptation..5/9

We found that after 2 successive generational exposures to hypoxia, worms were no longer long lived. After 4 successive generational exposures to hypoxia, worms no longer displayed a reduction in fertility. The worms adapted on a transgenerational scale to the repeated environmental stress! 4/9

We examined the effects of exposing successive generations to a stress we knew would induce epigenetic inheritance. Hypoxia exposure causes extended lifespan, reduced fertility, and reduced lipids and some of these phenotypes are heritable pubmed.ncbi.nlm.nih.gov/36516753/ 3/9

Recent work has demonstrated that a single exposure to a dramatic stress induces transgenerational phenotypes of altered color, obesity, glucose tolerance, behavior and longevity. But we are exposed to different environmental stresses each generation (changes in pesticides and fungicides etc) 2/9