As of 2013, we can neither cure nor prevent a single age-related disease. Even at our absolute best – and then only questionably and in one or two cases – can we even slow the unrelenting progress of any of our myriad age-related diseases. Trying for an optimistic view of current medical interventions, and even […]
The Status of Age-Related Disease
As of 2013, we can neither cure nor prevent a single age-related disease.
Even at our absolute best – and then only questionably and in one or two cases – can we even slow the unrelenting progress of any of our myriad age-related diseases. Trying for an optimistic view of current medical interventions, and even if we restrict our claims only to treating symptoms, we can offer only partial interventions at our best. Medical science offers a great deal – preventing and treating infections, safer surgery, better obstetrics, better therapies for diabetes to name only a handful of minor miracles – but we can do essentially nothing for age-related diseases To be fair, we often know very little of how these diseases work and perhaps far too much about their symptoms. Given what we do know, it’s easier to treat what we can understand – the symptoms – and what we know how to deal with, if only somewhat. Even our symptomatic interventions fall far short of what budgets and compassion demand of us: the costs are too high, the benefits too small.
Consider osteoporosis, a relatively simple age-related disease. We pretend we understand the pathology of the aging joint, but we do so with a wave of our hands – “the joint wears out, what can you expect?” – while we avert our eyes from any deeper understanding and walk past our own ignorance. If a joint wears out, WHY does it wear out when it does? Why in some people and not others? Why in some species and not others? Why in some joints and not others? Our treatments are better: we remove the old joint and we substitute an artificial joint. It isn’t perfect and certainly not as good as a young, healthy joint, nor does it last as long as a young, healthy joint, yet it is all we have – for now – and we try. But the average cost of an artificial joint approximates forty thousand dollars, requires surgery, surgical risk, painful recovery, and acceptance of what is only a partial solution.
Aging vessels – coronary artery disease, angina, heart attacks, strokes, congestive heart failure – are worse. While joints “just wear out”, our model of vessel disease is more complex, yet still frighteningly incomplete. We point the finger of blame at cholesterol, smoking, hypertension, and diabetes, not because these factors cause aging vessel disease, but because they are known to be correlated with these problems of our arteries as we age. Some children, those with Hutchinson-Gilford progeria, have atherosclerosis while having none of the “classic” risk factors; some adults have all of these risk factors, yet no evidence of atherosclerosis. Why? Not because our understanding of the pathology is wrong, but because our understanding is incomplete. Our treatments are equally incomplete and insufficient. At the extreme end, we can transplant vessels (or even hearts!), yet the outcome is not complete health – young vessels, or a young heart – only a temporarily better hold on a tenuous life. Yet what else can we offer? Quite a bit, actually, though still not a cure. We offer statins, anti-hypertensive medications, and a plethora of other drugs for the risk factors we hope we understand. We use drugs, trying to control the risk factors, such as diabetes, cholesterol, or blood pressure, but the outcome is still compounded of expense, side effects, and only a minimal improvement of our risks.
Alzheimer’s disease is worst: we have nothing to offer beyond a simple compassion. We cannot even offer hope: the average lifespan after the initial diagnosis of Alzheimer’s disease is seven years and we have nothing that is known to halt – or even slow – that inexorable slide as we lose our souls and fall towards our death. Once again, and despite correlations with beta amyloid and tau proteins, we not only don’t know what actually causes (rather than correlates with) the disease, we have no way to treat even those correlations. Every drug trial that has tried to remove or prevent amyloid deposits has failed clinically: we have yet to find a single effective intervention for amyloid, let alone slow Alzheimer’s disease itself. As with other age-related diseases, the outcome is expensive medical care – nursing homes prominent among those costs – but without even partial improvement. Alzheimer’s remains a disease without any treatment.
As we look over the state of care for all age-related diseases, the view is a pessimistic one. All of our treatments are maximally expensive and minimally effective. Why?
Not knowing what to treat, we treat what we can see; not knowing causes, we treat outcomes. But doing so – treating the downstream problems rather than the upstream causes – we find ourselves frustrated and disappointed when we can do so little – and at so high a cost. Could we do more if we understood the “causes” of aging? Perhaps, but the problem is not one of finding the cause of aging, but rather finding the most effective point of intervention. If we could understand the cascading problems that underlie the diseases of aging, where – what one single point perhaps – would be the single most cost-effective point to intervene? Or perhaps we could simply ask, what is the most effective (cost-effective or otherwise) place to cure and prevent the diseases of aging? Clearly, the most effective point to intervene is not vein replacement, statins, artificial knees, beta amyloid, or any of those dozens of random targets we aim at currently. We need a better understanding of aging and a better target for clinical intervention in the diseases of aging.
Aging is a process in which cells change their patterns of gene expression, a process which gradually brings on cell dysfunction, failing tissues, and the clinical diseases that so trouble us as we grow old. The pattern itself changes in response to the gradual loss of telomere segments at the ends of our chromosomes. It is not the length of the telomere itself, but the relative change in length that gradually alters gene expression and that culminates in human disease. While we might move a tiny bit “upstream” and strive to alter the patterns of methylation and acetylation that define those epigenetic changes, we now know that the single most effective point of intervention – not the cause, but the most effective target – is the telomere.
To date, research has shown that we can partially reset aging by using a small-molecule approach: astragalosides show a significant effect on the aging of the immune system, for example. While the results are promising, we are about to move forward with a far more powerful approach – the so-called large-molecule approach – and try to completely reset telomere lengths.
By aiming at the most effective single point of intervention, we will not only cure and prevent age-related disease, but we will prevent the tragedy and waste that result from disease and from aging itself.