Regulation of Proteins Plays an Important Role in Aging
Dr. Gordon Lithgow and colleagues at the Buck Institute’s Geroscience Consortium, one of nine interdisciplinary research consortia funded by the Common Fund, have discovered that the translation of key proteins may underlie the ability of long-lived mutant worms to survive extreme heat conditions that are fatal to normal worms. Translation is a cellular process that makes proteins from a type of genetic material known as RNA, and by altering this process, long-lived worms may be protected from environmental stresses like heat. This ability to withstand environmental stress is thought to be related to the worms’ increased longevity, and thus discoveries about how these long-lived worms withstand stress may also be helpful for understanding the process of aging.
Why study worms?
The biological study of aging is a complex and interdisciplinary field, with researchers studying how environmental stresses, genetic changes, and diet can impact lifespan. Worms, such as the commonly used laboratory model C. elegans, are a valuable research model for aging studies because they have a short lifespan (typically two to three weeks) that can easily be observed in the laboratory. Additionally, many factors that increase lifespan in worms, such as dietary restriction, also appear to improve health and increase lifespan in monkeys and people. There are many different types of mutant worms that are resistant to environmental stress and have increased lifespan. The long-lived mutant worms in this study are genetically modified so they are less responsive to insulin, a hormone that regulates metabolism. It is well-known that decreases in insulin responsiveness result in longer lifespan in worms, but the exact reason why is unclear.
New ideas about aging
Inside each cell, genes encoded by DNA are first copied into RNA in a process known as transcription. After transcription, RNA is translated into proteins. Many previous studies on long-lived worms had attributed their ability to withstand environmental stresses on changes in transcription. While transcription undoubtedly plays an important role in protection from stress and increased longevity, this study demonstrates that translation of key proteins is critical for surviving extreme heat and contributes to increased lifespan in long-lived worms. This discovery suggests a novel pathway through which insulin affects lifespan by regulation of key proteins in the cell. A better understanding of insulin responsiveness, protein regulation, and protection from environmental stress may lead to new insights on how to increase longevity and promote healthy aging.
McColl G, Rogers AN, Alavez S, Hubbard AE, Melov S, Link CD, Bush AI, Kapahi P, Lithgow GJ. Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans. Cell Metab. 2010 Sep 8;12(3):260-72. PMID: 20816092