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Science AMA Series: Hi, reddit! I’m Will Mair, assistant professor of genetics and complex diseases at Harvard T.H. Chan School of Public Health, and my lab recently found a causal link between RNA splicing and aging
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Abstract

Hello, reddit! My name is William Mair, and I’m an assistant professor of genetics and complex diseases at Harvard T.H. Chan School of Public Health. My lab recently published a paper in Nature which, for the first time, reveals a causal link between a process known as “RNA splicing” and aging. This research sheds important light on when and how our cells deteriorate over time. Aging is a key risk factor for a variety of chronic diseases, and our lab is working to identify what’s happening at the molecular level in various organ systems that allows these diseases to occur. What is RNA splicing? In order for bodies—and cells—to maintain youthfulness, they must also maintain proper homeostasis. At the cellular level, that means keeping the flow of biological information, from genes to RNA to proteins, running smoothly and with the right balance. While a considerable amount is known about how dysfunction at the two ends of this process—genes and proteins—can accelerate aging, strikingly little is known about how the middle part, which includes RNA splicing, influences aging. Splicing enables one gene to generate multiple proteins that can act in different ways and in disparate parts of the body. To find this link, we designed a series of experiments in the roundworm Caenorhabditis elegans to probe the potential connections between splicing and aging. Because the worms’ cells are transparent we were able to use fluorescent genetic tools to visualize the splicing of a single gene in real-time throughout the aging process. After five days, some worms showed a youthful pattern of splicing while others exhibited one indicative of premature aging. We were able to use these differences in splicing (reflected fluorescently) to predict individual worms’ lifespans prior to any overt signs of old age. We still have much more to learn about this, but the findings open up an entirely new avenue of investigation that could help us understand how to live longer and healthier. I’ll be here to answer your questions from 11:00 AM to 1:00 PM EST; Ask Me Anything! EDIT: It’s 11:00 AM and we’re getting underway. Thanks for all your questions so far! I’m also joined here by /u/carolineheintz, the first author of the paper. EDIT: It’s 1:17 PM and we have to stop, but thank you for your great questions! If you want to learn more, you can visit our lab website.