Better living through self-destruction

In their review “Autophagy and aging: the importance of maintaining ‘clean’ cells”, published in the upcoming issue of the relatively new journal Autophagy, Cuervo and colleagues discuss the age-related decline in the efficiency of multiple autophagic pathways:

A decrease in the rate of protein turnover and the intracellular accumulation of altered proteins in cytosol and membranes are features common to all aged cells. Diminished autophagic activity plays a major role in these age-related manifestations. In this work we review the molecular defects responsible for the malfunctioning of two forms of autophagy – macroautophagy and chaperone-mediated autophagy – in old mammals, and highlight general and cell-type specific consequences of dysfunction of the autophagic system with age. Dietary caloric restriction and antilipolytic agents have been proven to efficiently stimulate autophagy in old rodents. These and other possible restorative efforts are discussed.

This article forced me to amend my view of the role of autophagy in aging, which was subtly wrong: In my prior tacit model, undesirable proteins are cleared with an efficiency that is less than 100% but constant over the lifespan of the cell, resulting in an essentially linear accumulation of detritus. In the new model, age-related changes decrease the efficiency of the clearance process, and the rate of accumulation of cellular rubbish will increase dramatically with time.

Especially if the steady-state level of altered protein directly interferes with autophagy (one way that the passage of time could result in a decreased autophagic efficiency), this is reminiscent of the now-discredited (but still kicking) error-catastrophe theory of aging. Indeed, the application of error-catastrophe logic to the accumulation of damaged macromolecules has been termed the garbage catastrophe theory of aging.