The Prospects for Enhancing Autophagy to Combat Age-Related Degeneration

You'll find a rather interesting paper (abstract and full PDF are available) at the Annals of the New York Academy of Sciences on the topic of manipulating autophagy to repair some classes of age-related damage to cells and cellular components.

Aging denotes a post-maturational deterioration of cells and organisms with the passage of time, an increased vulnerability to challenges and prevalence of age-associated diseases, and a decreased ability to survive. Causes may be found in an enhanced production of reactive oxygen species (ROS) and oxidative damage and not completed housekeeping.

Caloric restriction is the most robust anti-aging intervention known so far. Similar beneficial effects on median and maximum life-span were obtained by feeding animals a 40% reduced diet or by every-other-day ad libitum feeding. In both instances, animals are forced to spend a great part of their time in a state of fasting and activated autophagy.

Autophagy is a highly conserved process in eukaryotes, in which the cytoplasm, including excess or aberrant organelles, is sequestered into double-membrane vesicles and delivered to the lysosome/vacuole, for breakdown and eventual recycling of the resulting macromolecules.

This process has an essential role in adaptation to fasting and changing environmental conditions, cellular remodeling during development, accumulation of altered ROS-hypergenerating organelles in older cells. Several pieces of evidence show that autophagy is involved in aging and is an essential part in the anti-aging mechanism of caloric restriction.

As an application, intensification of autophagy, by the administration of antilipolytic drug, rescued older cells from accumulation of altered [mitochondrial] DNA in less than 6 hours. It is concluded that the pharmacological intensification of autophagy [has] anti-aging effects and might prove to be a big step towards retardation of aging and prevention of age-associated diseases in humans.

Autophagy is a form of maintenance, the first step in the process of replacing damaged components with newly built components. It is promising that even today there are tools that could be applied to enhancing that process, or more likely serve as a starting point for the development of better, safer tools in the years to come.

You'll find more on autophagy as a process and its relationship to aging, mitochondria and calorie restriction back in the Fight Aging! archives:


The criteria for defining is very interesting. I take note with the 'post-maturational' criterion in particular. Why? Can cells or organisms not degenerate prior to their maturation? I think they do. Obviously, humans don't need to finish growing or even hit puberty (or even exit the womb, I think) before their metabolism is generating free radicals and existing in a world full of contaminants and dangers which can upset their genetic codes and other important mechanisms. You are 'dying since birth' so to speak. There is evidence enough of problems when you look at cases of juvenile cancer or progeria.

Such criteria is even worse when applying to a cell, since they are constantly dividing, and as such constantly being reborn and 'maturing' until they reach full size. If one were to only analyze cells for problems when fully grown, one would miss all sorts of potential dangers that might occur at the start of a cell's life cycle.

Posted by: Tyciol at October 30th, 2007 10:38 AM

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