Curing Disease: More Insight Instead of Mere Effort
Curing disease correlates with insight, not blind effort. An eternal trade-off exists between insight and effort. If we think carefully, understand the problem, and plan, then the effort is minimized. If (as too often happens) we think carelessly, misunderstand the problem, and rely on hope instead of planning, then the effort is not only maximized but is usually a complete waste.
Lacking insight, we foolishly flush both money and effort down the drain. In the case of clinical trials for Alzheimer's disease – and in fact, all age-related diseases – this is precisely the case.
The major problem is a naïve complacency that we already understand the pathology of aging. If there were a single concept that is key to all of aging, it is the notion that everything in our organs, tissues, and cells is dynamically and actively in flux, rather than a set of organs, tissues, cells, and molecules that deteriorate statically and passively. Aging isn't just entropy; aging is entropy with an insufficient biological response.
Senescent cells no longer keep up with entropy, while young cells manage entropy quite handily. At the tissue level, the best example might be bone. We don't form bone and then leave it to the mercy of entropy; rather, we continually recycle bony tissue throughout our lives – although more and more slowly as our osteocytes lose telomere length. This is equally true at the molecular level, for example, the collagen and elastin molecules in our skin.
We don't finish forming collagen and elastin in our youth and then leave them to the vagaries of entropy; rather, we continually recycle collagen and elastin molecules throughout our lives, though more slowly as our skin cells lose telomere length. Aging is not a process in which a fixed amount of bone, collagen, or elastin gradually erodes, denatures, or becomes damaged. Rather, aging is a process in which the rate of recycling of bone, collagen, or elastin gradually slows as shortening telomeres alter gene expression, slowing molecular turnover and letting damage get ahead of the game. We don't age because we are damaged; we age because cells with shortening telomeres no longer keep up with the damage.
The same is true not only of biological aging as a general process, but also of every age-related disease. Vascular disease is not a disease in which our arteries are a static tissue that gradually gives way to an erosive entropy, but an active and dynamic set of cells that gradually slow their turnover of critical cellular components, culminating in the failure of endothelial cell function, the increasing pathology of the subendothelial layer, and the clinical outcomes of myocardial infarction, stroke, and a dozen other medical problems. Merely treating cholesterol, blood pressure, and hundreds of other specific pathological findings does nothing to reset the upstream epigenetic changes that cause those myriad changes. Small wonder that we fail to change the course of arterial disease if our only interventions are mere "stents and statins".
Nor is Alzheimer's a disease in which beta amyloid and tau proteins passively accumulate over time as they become denatured, resulting in neuronal death and cognitive failure. Alzheimer's is a disease in which the turnover – the binding, the uptake, the degradation, and the replacement – of key molecules gradually slows down with telomere shortening, culminating in the failure of both glial cell and neuron function, the accumulation of plaques and tangles, and ending finally in a profound human tragedy. The cause is the change in gene expression, not the more obvious plaques and tangles.
More Insight is Needed
Our lack of insight, even when we exert Herculean efforts – enormous clinical trials, immense amounts of funding, and years of work – is striking, given the complete failure of many clinical trials aimed at Alzheimer's disease. Naively, we target beta amyloid, tau proteins, phosphodiesterase, immune responses, and growth factors, without ever understanding the subtle upstream causes of these obvious downstream effects. Aging, aging diseases, and especially Alzheimer's disease are not amenable to mere well-intended efforts. Without insight, our funding, time, and effort are useless. Worse, that same funding, time, and exertion could be used effectively if applied intelligently.
If our target is to cure the diseases of aging, then we don't need more effort, but more thought. However well-intentioned, however much investment, however many grants, and however many clinical trials, all will be wasted unless we understand the aging process. Aging is not a passive accumulation of damage, but an active process in which damage accumulates because cells change their patterns of gene expression, patterns which can be reset. Curing Alzheimer's requires insight and intelligence, not naive hope and wasted effort.
Contributing Author: Dr. Michael Fossel earned both his Ph.D. and MD from Stanford University, where he taught neurobiology and research methods. Winner of a National Science Foundation fellowship, he was a clinical professor of medicine for almost three decades, the executive director of the American Aging Association, and the founding editor of Rejuvenation Research. In 1996, he wrote the first book on the telomerase theory of aging, Reversing Human Aging, describing the medical aspects of extending human telomeres, reversing aging, and curing age-related disease. In 2004, he authored the academic textbook Cells, Aging, and Human Disease, and in 2011, he coauthored The Immortality Edge, a bestselling discussion of the potential to extend the human lifespan. He currently serves as Chairman of the Board of Telocyte, a biotechnology company developing telomerase therapy for Alzheimer's disease, with planned FDA-sponsored human trials aimed at targeting the underlying disease process.
Disclaimer: Dementia Society of America (DSA) provides educational content only and does not offer medical advice. Always consult a qualified healthcare professional before changing your medical care. DSA content is created by both human and computer-generated means and is reviewed for accuracy; however, errors may occur. Views expressed by third-party contributors do not necessarily reflect those of DSA. Unless expressly stated, DSA does not endorse or guarantee any third-party products, services, organizations, or external content. All DSA content is copyrighted and/or trademarked and may not be used without written permission.
Comments