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SAGE KE Bulletin Board

Map of Age-Dependent Phenotypes

5 August 2002

ALex F. Bokov

Goals: This is an attempt to synthesize the vast amounts of fascinating information being presented at the 2002 Molecular Biology of Aging Course at the Woods Hole Marine Biology Laboratory. Seeing the individual components in the context of a big picture will help participants better retain the information that was presented to them. I hope this will also be useful to those who haven't been at the course, because they will be able to see where their own research fits into the big picture. As time permits, I will link portions of this map to abstracts of articles containing empirical evidence for/against the causal relationships (arrows) and possible age-related phenotypes (words) in the map below. Items with few linkages will come to indicate questions that haven't been adequately studied yet and may therefore be sources of ideas for new research topics.
I make no claim of accuracy or completeness. I've tried to properly attribute the ideas people have given me so far, but I don't imply endorsement by those individuals, and any omissions in this are my own... and hopefully you'll help me fix these omissions; I actively solicit your criticism. Since the image-map this post links to is off-site, I'll be able to update it, and the next time you view this post you might see a different picture. At this early stage, I'm particularly interested in whether anybody can think of any classes of age-related phenotypes (see below) besides the three represented by boxes on the diagram. Also, are there any age-related phenotypes that are omitted from the diagram, or are redundant, or whose meaning is unclear? Please send your feedback to p8q2z001{at}sneakemail.com?subject=Aging%20Map.

Important Note: A far better "aging map" already exists elsewhere and has been brought to my attention. Pending the author's permission, I will link to this image map in the future. Please chack back soon.

Explanation of map: during Thomas Kirkwood's talk at MBL, one of the students asked him something to the effect of "what makes a mutation manifest itself at a late age?". To this he responded that it's not a programmed process (like development), and therefore he wouldn't expect "aging genes" to get abruptly turned on at age 50 or 60. Rather, aging phenotypes result from gradual accumulation of damage that repair/defense mechanisms can't quite keep up with. They can't keep up with the damage they're supposed to be repairing because there is only a selective advantage in their being efficient enough to let the animal live out the lifespan permitted to it by predators, scarce food supply, and the risk of accidental death inherent in the conditions it evolved under (for a much more detailed and eloquent explanation, please see Why do we age?, Nature 408, p233). That started me thinking about what other ways there could be an "aging clock" without stipulating programmed mechanisms. I've only been able to think of two others, which I'm sure many have thought of before me. This brings the total number to three:
  1. Accumulation The process of inadequate damage repair described by Dr. Kirkwood. I'd add to that inadequate turnover of both damaged molecules and normal molecules collecting in excess (again, this is a long-time idea in aging and I make no claims of originality).
  2. Depletion The process whereby a needed substance, structure, or tissue is depleted.
  3. Microevolution Like accumulation, except at an accelerating rate, because the accumulating item is at a replicative advantage. The best-established example of this are cells that have escaped from cell-cycle control and/or contact inhibition.

The list of items at the center of the map is not restricted to any given class of age-dependent phenotype. They are just general forces that most likely influence multiple age-dependent phenotypes in multiple classes.

Thank you for your patience in reading this far. Again, your feedback is welcome either in the form of a reply to this topic or an p8q2z001{at}sneakemail.com?subject=Aging%20Map.

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Science of Aging Knowledge Environment. ISSN 1539-6150