Do you want to live long? Do autophagy, not sex!
Despite the active search for the causes of aging, the molecular mechanisms underlying it are largely unclear. Researchers at the Sanford-Burnham Medical Research Institute (California), working under the direction of Malene Hansen, are studying these mechanisms on a popular model organism – the roundworm Caenorhabditis elegans.
They found that the lifespan of these worms is formed by the action of two intracellular processes: lipid metabolism and autophagy. Autophagy, the main mechanism that a cell uses to recycle worn–out and damaged components, has attracted strong interest from scientists in recent years. It turned out that this mechanism, as well as its disorders, is involved in the development of many human diseases, including cancer and Alzheimer's disease.
In their work, the authors used genetically modified nematodes that do not have germ line cells (germ cells), whose life expectancy, for reasons not fully understood, exceeds the life expectancy of normal individuals of this species by 25%. The obtained results showed that the aging-slowing effect of autophagy is due to the stimulation of the activity of a fat-splitting enzyme.
Despite their inability to reproduce, these worms have sex glands that produce lipids necessary for the development of eggs, in this case, non–existing ones. The results of the study showed that, perhaps, due to the excessive amount of lipids in need of disposal, these worms are characterized by abnormally high activity of the autophagy process.
The green fluorescence in the image signals the intensity of autophagy processes in C.elegans cells
(here they are magnified many times: in fact, the length of this worm is about 1 mm).
The increased activity of the lipid-splitting enzyme of such worms was previously associated with an increased lifespan, but the underlying mechanisms of this phenomenon were unclear.
The researchers found that autophagy activity is a prerequisite for maintaining a high level of LIPL-4 enzyme activity, which, in turn, is necessary to trigger autophagy.
In the end, they linked both events to an important regulatory protein whose activity is reduced in the studied model – the TOR protein (target of rapamycin, from the English Target of Rapamycin), which registers the intake of nutrients into the body and is involved in the processes of metabolism and aging of many species.
According to the researchers, by and large, the revealed pattern is a "supply and demand problem". Usually, if an excess of lipids appears in the worm's body, it is deposited in the form of fat deposits.
In the studied long-lived model, activation of a seemingly meaningless cycle of lipid cleavage and re-synthesis takes place. However, as it turned out, the breakdown of lipids by autophagy gives this cycle an unexpectedly deep meaning.
The researchers believe that their findings will shed light on the molecular mechanisms of the development of age-related diseases, such as diabetes, cancer and neurodegenerative diseases. In the near future, they plan to continue their work on studying the relationship between autophagy and the LIPL-4 enzyme, as well as finding out the details of its effect on fat metabolism. They are also interested in identifying the possible existence of similar mechanisms in representatives of other species.
Article by Lapierre et al. Autophagy and Lipid Metabolism Coordinate Modulate Life Span in Germline-less C. elegans is published in the preliminary on-line version of the journal Current Biology.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru / based on the materials of Sanford-Burnham Medical Research Institute: Recycling Fat Might Help Worms Live Longer.
20.09.2011