Researchers at Yeshiva University have used transgenic mice to turn on a process that helps keep the liver of older mice young and healthy. Using a double transgenic mouse model that could be modulated to selectively increase the number of receptors for damaged proteins, they found that the process of chaperone-mediated autophagy (CMA) could be controlled to allow mice to continuously degrade and recycle proteins that accumulate with old age. Functionally, this could have significance for diseases like Alzheimer’s or Parkinson’s.
Professor Ana Maria Cuervo has shown that lysosome function is a crucial part of the ageing process. Cuervo has also shown, he says, the critical role the lysosomal receptor molecules play in keeping the liver clean of damaged proteins.
Lysosome buildup removal is one the seven parts of SENS The lysosens project is targeted at removing the lysosome buildup.
Aubrey de Grey, Methuselah Foundation Chairman and Chief Science Officer and the founder of the SENS (Strategies for Engineered Negligible Senescence) program, is good friends with the senior author. Aubrey says “It’s the result of the year – sensational.”
Thomas von Zglinicki, Professor of Cellular Gerontology at Newcastle University, said that the results were “very exciting”. “It’s not often you see studies where they have managed to improve function in this way. “What they seem to have managed is to maintain the mice at this young stage, and both restore and maintain normal activity.” He said that it should, in theory, be possible to achieve the same effect across the whole body.
A spokesman for the Alzheimer’s Society said: “As we age we have an increase in protein misfolding and general faults in protein processing, so the ability to maintain an effective system to clear these would be beneficial.
The Nature Medicine article: Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function
egradation of cytosolic proteins in lysosomes, contributes to the removal of altered proteins as part of the cellular quality-control systems. We have previously found that CMA activity declines in aged organisms and have proposed that this failure in cellular clearance could contribute to the accumulation of altered proteins, the abnormal cellular homeostasis and, eventually, the functional loss characteristic of aged organisms. To determine whether these negative features of aging can be prevented by maintaining efficient autophagic activity until late in life, in this work we have corrected the CMA defect in aged rodents. We have generated a double transgenic mouse model in which the amount of the lysosomal receptor for CMA, previously shown to decrease in abundance with age, can be modulated. We have analyzed in this model the consequences of preventing the age-dependent decrease in receptor abundance in aged rodents at the cellular and organ levels. We show here that CMA activity is maintained until advanced ages if the decrease in the receptor abundance is prevented and that preservation of autophagic activity is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function.
Fightaging has coverage of this development as well