You Are Not Only As Old As You Think You Are
The Archives of Neurology devoted its November 2002 issue to "aging of the nervous system." Eight fascinating reviews by "major figures in the field" were accompanied by three original contributions about Parkinson disease and three about Alzheimer disease. An excellent summary of research findings was presented by the editor, Roger N. Rosenberg, MD from the University of Texas Southwestern Medical Center. I chose his editorial as the major source for this article since I feel that it will provide my readers with deeper insight into why Doctor Rosenberg called his observations "Time and Memory."
Obviously, as each species develops from its early origins into a more and more adaptable form by means of mutations and natural selection, the main objective is to perpetuate the species. Once the reproductive age has passed there is little evolutionary reason to keep survivors alive. The reasons for expending "genetic energy" have now passed and little effort is made to overcome those illnesses associated with aging. The nervous system participates in this downward trend so that the end result may well be one of those diseases we usually ascribe to old age including cerebrovascular disease, Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis (Lou Gehrig disease), the frontotemporal dementias, and progressive brain atrophy. This topic was covered by George M. Martin in his review called "The Evolutionary Substrate of Aging."
The next subject recognized the important role played by molecular genetics and genomics. Longo and Finch discussed this aspect in their review called "Genetics of Aging and Diseases: From Rare Mutations and Model Systems to Disease Prevention." Here, once again, we run into that all pervasive new concept of apoptosis in which the tissues are molded via cell loss. The neurons of the nervous system are no exception to these alterations which are probably accompanied by such things as free radical formation and oxidative stress, telomeres and telomerases, genes controlling cell cycling, and cell membrane signal transduction pathways now under intensive study. We now know a great deal more about genes involved in Alzheimer disease and Parkinson disease. This is leading to new treatment modalities.
One of the more promising approaches to treating Alzheimer disease is directed at it's overproduction of amyloid. Various ways to do this involve reducing the "Aß40/42 burden in patients brains." This can be done by reducing its synthesis or by means of inhibitors. One apparently promising approach has been Aß vaccination, but this method has stalled due to reports of encephalitis seen in clinical cases. Suggested for future more intensive study are the essential enzymes that protect against aging such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Work is also being done on the effects of oxidative stress, and dietary restriction of calorie intake. Linkages have been shown between resistance to oxidative stress and longevity in mice. Consistent with a reduced level of oxidative stress is the finding that restricting calories in invertebrates and mammals leads to longer life. Rosenberg suggests that a search for the genes responsible for this effect might lead to better understanding of human brain aging.
For those of you who worry about changes in your memory and mental capability, as you get older, the answers at present are only speculative. Is there a progression from normal aging to mild cognitive impairment and finally Alzheimer disease? Are we dealing with a single disease, which is gradually evolving at a quantitative rate? Apparently, if this is so, different individuals convert from one stage to the other at different rates depending on penetrance of the disease process. However, it is not yet known whether we are really dealing with two different processes. Perhaps one condition merely predisposes to the other in a qualitative fashion. No biochemical marker has yet been found to link the two conditions. Work by Riemenschneider et al in this issue appears to confirm that certain proteins in the cerebrospinal fluid become more abnormal as patients convert from milder to more severe stages. This is suggestive evidence favoring a direct linkage, but certainly not proof. In any event, about 12% to 15% of mild cognitive impairment patients develop clinical Alzheimer disease every year.
Evidently there is a great deal to be learned as to why aging takes place, what role is played by our genetic makeup, why different animals age at different rates, what enzymes may be involved and how, what is the relationship to atrophy of the hippocampus or the entorhinal cortex of the brain at varying rates and in different groups of the aging populace, what role is played by dietary and other environmental factors, etc. We are only at the threshold of discovery and the possibility of therapy.
And now I would like to ask you, is this what we really want? Is it a good thing to expand the population still further from both ends by having more children and keeping our older people alive? Even if it's good to stay alive longer, doesn't this depend on the quality of life experienced during those additional years? In other words, do you want to live a few years longer just to be around longer, even if those years might be spent in increasing discomfort?
Something's creeping up on me,
Could it be my underwear?
No matter if I pull it out,
Somehow seems it's always there.
Why does everyone talk so low,
Mumble, mumble in my ears?
Can't they turn the volume up,
Blow some horns, shift some gears?
Got trouble gettin' outa chairs,
What in heck did I want to do?
Got trouble gettin' down the stairs,
Lead in my pants, glue on my shoe.
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Cartoons and Poems following each article are created and copyrighted by Dr. Ackerman and cannot be copied or reproduced without his permission.
Copyright © 2005 by Marvin Ackerman, M.D.