Aging Cast As Autophagy Disorder
Enhanced autophagy is clearly important in most - possibly all - of the demonstrated ways to extend healthy longevity in mammals. I noticed this paper today: "Many macromolecules under degradation inside lysosomes contain iron that [makes] lysosomes sensitive to oxidative stress. ... Apart from being an essential turnover process, autophagy is also a mechanism for cells to repair inflicted damage, and to survive temporary starvation. The inevitable diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow oxidative formation of lipofuscin in long-lived postmitotic cells, where it finally occupies a substantial part of the volume of the lysosomal compartment. This seems to result in a misdirection of lysosomal enzymes away from [autophagic vacuoles], resulting in depressed autophagy and the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. This scenario might put aging into the category of autophagy disorders."