Secrets of the Cell - Self-Destructive Behavior in Cells May Hold Key to a Longer Life - Carl Zimmer - NYTimes.comAs best I can remember, this is all new since I did med school in the early 80s. Anything that can clear huntingtin is exciting all by itself, no matter how preliminary the research.
...lysosomes are versatile garbage disposals. In addition to taking in shrouded material, they can also pull in individual proteins through special portals on their surface. Lysosomes can even extend a mouthlike projection from their membrane and chew off pieces of a cell.
The shredded debris that streams out of the lysosomes is not useless waste. A cell uses the material to build new molecules, gradually recreating itself from old parts. “Every three days, you basically have a new heart,” said Dr. Ana Maria Cuervo, a molecular biologist at Albert Einstein College of Medicine...
...The protection humans get from lysosomes is essential not just during famines. It is also vital just after birth. When babies emerge from their mothers, they need huge amounts of energy so that they can start to run their bodies on their own. But this demand comes at precisely the moment that babies stop getting food through their umbilical cord. Japanese scientists have found that lysosomes in mice kick into high gear as soon as they are born. After a day or two, as they start to nurse, the rate of autophagy drops back to normal.
When the scientists engineered mice so they could not use their lysosomes at birth, the newborn mice almost immediately died of starvation...
... It has long been known, for example, that animals that are put on a strict low-calorie diet can live much longer than animals that eat all they can. Recent research has shown that caloric restriction raises autophagy in animals and keeps it high. The animals seem to be responding to their low-calorie diet by feeding on their own cells, as they do during famines. In the process, their cells may also be clearing away more defective molecules, so that the animals age more slowly...
... Andrea Ballabio, the scientific director of Telethon Institute of Genetics and Medicine in Naples, Italy, and his colleagues have found another way to raise autophagy. By studying the activity of genes that build lysosomes, they discovered that at least 68 of the genes are switched on by a single master protein, known as TFEB.
When Dr. Ballabio and his colleagues engineered cells to make extra TFEB, the cells made more lysosomes. And each of those lysosomes became more efficient. The scientists injected the cells with huntingtin, a protein that clumps to cause the fatal brain disorder Huntington’s disease. The cells did a much better job of destroying the huntingtin than normal cells...
Terrific stuff.
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