A new target for the development of drugs against age-related diseases

One of the key proteins affecting the aging process has been discovered

LifeSciencesToday based on materials from Sanford-Burnham Medical Research Institute:
A new target for the development of therapeutics against age-related disordersScientists from the Sanford-Burnham Medical Research Institute have discovered one of the key factors in the regulation of the autophagy process - the mechanism of cell purification that destroys biochemical cellular "garbage" and protects cells from damage, which in turn affects the aging process.

The results of this study, published in the journal Nature Communications (Lapierre et al., The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans), may lead to the development of new treatments for age-related diseases characterized by a violation of the autophagy process.

Malene Hansen, PhD, associate professor at the Del E. Webb Center for Neuroscience, Aging and Stem Cell Research (Del E. Webb Center for Neuroscience, Aging and Stem Cell Research), and her group discovered a transcription factor – a switch of gene activity – inducing the process of autophagy in the cells of model animals, including among the nematodes of C.elegans, the main model organism studied in Dr. Hansen's laboratory. This transcription factor, called HLH-30, coordinates the autophagy process by regulating the activity of genes with functions implemented at various stages of the process. Two years ago, researchers discovered a similar transcription factor, or orthologue, called TFEB, which regulates autophagy in mammalian cells.

"HLH-30 is crucial for the longevity of all the long–lived C. elegans strains we have tested," says Dr. Hansen. "In order to increase the lifespan of these models, possibly due to autophagy, it is necessary that HLH-30 be active. We found this activity not only in long-lived worm models, but also in mice on a limited diet, and we assume that this mechanism can be preserved in more highly developed organisms."

HLH-30 is the first transcription factor functioning in all known autophagy-dependent paradigms of longevity, which strengthens the position of the new concept that autophagy contributes to an increase in life expectancy. In one of the previous studies, Dr. Hansen and her colleagues found that enhanced autophagy has an anti-aging effect, possibly by stimulating the activity of an associated enzyme that breaks down fats. Thus, scientists now know one of the key components of autophagy regulation in aging.

Now Dr. Hansen's group is searching for therapeutic targets, in particular, overlying kinases – molecules that alter the functions of proteins – that can phosphorylate this transcription factor.

"We already have one clue – the TOR protein, the main regulator affecting metabolism and aging in many species – but there may be other kinases regulating the activity of HLH-30 or TFEB," says lead author of the study Louis René Lapierre, PhD, postdoctoral fellow at the Hansen laboratory.

Overview of TOR-regulated processes with evolutionarily preserved effects on the aging process. TOR inhibition increases the lifespan of several model organisms by affecting a number of biological processes, including protein translation, cellular recycling – autophagy, metabolism and stress responses. (Fig. sanfordburnham.org )

Autophagy has become the subject of intensive study in the last few years, especially after this process – or its breakdown – has been closely associated with many human diseases, including cancer, cardiovascular diseases, Alzheimer's disease and other neurodegenerative diseases. The HLH-30 and TFEB transcription factors may represent attractive targets for the development of new therapeutic agents for the treatment or prevention of these diseases.

Portal "Eternal youth" http://vechnayamolodost.ru12.08.2013