Dr. Malene Hansen, associate professor at the Del E. Webb Neuroscience Center at the Sanford-Burnham Medical Research Institute, and her research team and collaborators discovered that a transcription factor in several animal models such as nematodes induces autophagy. This transcription factor, called HLH-30, coordinates the process of autophagy by regulating genes that play a role in several different steps of this process. Two years ago, researchers discovered that a similar transcription factor, TFEB, regulates autophagy in mammalian cells.
Hansen said: "HLH-30 is the key to ensuring longevity of all the longevity nematodes we tested. These models require active HLH-30 to prolong lifespan, which may induce autophagy. We found that this activation is not only present in the longevity nematode model. In addition, it also exists in diet-restricted mice, so we propose that this mechanism may be conserved in higher organisms. "
HLH-30 is the first transcription factor reported to function with all known autophagy-dependent longevity paradigms, reinforcing this emerging view that autophagy can promote longevity. In a past study, Hansen and colleagues found that increased autophagy has an anti-aging effect, which may be achieved by promoting the activity of an autophagy-associated lipolytic enzyme. Through these studies, scientists now know a key element that regulates autophagy during aging.
The Hansen research team is now working on finding therapeutic targets, especially upstream kinases that can alter protein function. "We have obtained some clues about the TOR protein, a major regulatory factor that affects the metabolism and aging of many species, but there should be other kinases that also regulate the activity of HLH-30 and TFEB," the main author of the paper, Hansen Said Louis René Lapierre, a postdoctoral researcher in the laboratory.
In the past few years, autophagy has become a hot spot in scientific research, and this process has been confirmed to be related to many human diseases including cancer, Alzheimer's disease, cardiovascular disease and neurodegenerative diseases. HLH-30 and TFEB may represent attractive targets for the development of new therapeutic drugs to deal with these diseases.
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