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aging

Is Aging a Disease?

Is Aging a Disease?

Teaser: 

Anna Liachenko, BSc, MSc,
Managing Editor,
Geriatrics & Aging

We take for granted that aging is a natural process. We accept this belief, even as we witness the disease-driven ravages of old age. We separate the diseases of old age from the process itself, as if the diseases of old age take place against a backdrop of biological changes that are somehow removed and independent of the diseases themselves. This separation of the two--aging and the classic diseases of the elderly--may be false and may undermine our ability to understand the real nature of aging.

A number of extraordinary new studies may forever jettison this dichotomy between the diseases that seem to characterize old age and the so-called natural process of aging. Some of the diseases that are characteristic of old age are senile dementia, cataracts, arteriosclerosis, cancer, diabetes, hypertension, osteoporosis, etc. We need to ask whether these diseases are a normal part of the aging process. Alternatively , we could pose the more counter-intuitive and, perhaps, more difficult question, "Is aging a Disease"?

Two recent studies offer unprecedented insight into the genetics of aging, along with evidence for a "general and global explanation of the process itself". If correct, these studies are suggesting that a small set of genes involved in cell division might have broad effects throughout the body and cause the wide spectrum of phenotypic, metabolic, physiological and cellular changes that we associate with aging.

These aging studies are based upon a revolutionary new technology, known as microarrays or, as they are called in the popular press, "gene chips". The reference to chips and microchips is not a misnomer. Gene chips are actually based upon the same technological principles and same technologies that are used in making silicon-based chips. Silicon fabrication technology and various photolithographically-layered masks are used to lay down thousands, or even hundreds of thousands of oligonucleotides of DNA on a postage-stamp-size piece of glass; amplified genetic samples can then be hybridized with these pieces of DNA. Using lasers to scan the chips, an enormous amount of genetic information can be ascertained. This technology promises for biology some of the extraordinary economies and efficiencies that have transformed all of electronics. The implications for aging research could be enormous.

The study supports a possible global explanation of aging as "an impairment of the machinery needed for the normal separation of the chromosomes during cell division."

In the March 31, 2000 edition of Science (page 2486), Richard Lerner and Peter Schultz report the use of microarrays to take a snapshot of aging-related changes in fibroblasts. The study supports a possible global explanation of aging as "an impairment of the machinery needed for the normal separation of the chromosomes during cell division." The study makes note of an "up-regulation of genes involved with inflammation, which has been linked with a variety of ills of old age, including heart disease and Alzheimer's" (in this regard, it may be supporting the recently-confirmed efficacy of NSAIDs and COX-2 inhibitors). Perhaps even more interesting is the "down-regulation of 15 genes that help control mitosis". These genes are "known to cause genetic instability, a known contributor to cancer." The author of the study, Richard Lerner is quoted as saying that "aging is predominantly a disease of mismanagement of cell division checkpoints". The gene chip study also seems to confirm increasing evidence that a very small percentage of our total genetic endowment plays a role in aging. The researchers found that of the 6,300 genes checked, only 63 genes changed with age. This small ratio of age-related gene expression coincides with an important study by Richard Weindruch and Tomas Prolla of the University of Wisconsin, who used microarrays to probe aging in the skeletal muscle of mice (Science 27, August 1999, p. 1390). In this study, it was found that less than 1% of those genes assayed increased or decreased activity.

Perhaps of even deeper interest to the whole question of whether aging is a disease, is the work performed by the Scripps team, comparing aging fibroblasts with fibroblasts from children suffering from Hutchinson-Gilford's progeria. A rare condition, that is caused by a single gene defect, Hutchinson-Gilford children experience what, phenotypically, seems to be an accelerated form of aging. That a single genetic defect could cause such a wide spectrum of aging-related alterations, has long been a source of curiosity and interest. These children appear old at ten years of age and rarely live past their eighteenth birthday.

The Scripps study seems to confirm that Hutchinson-Gilford patients do not just mimic aging phenotypically, but that they are indeed experiencing accelerated aging. This extraordinary result lays out part of what might emerge as a genetic program that dictates the aging process. Apart from outward manifestations of aging, Hutchinson-Gilford victims experience rapid onset of old skin, hair loss, arteriosclerosis, cancer, osteoporosis and hypertension. These results force us to ask whether these diseases, the diseases that take the largest toll on humanity, are, perhaps, part of the pathophysiology of aging.

These results are fascinating and as genetic chip technologies advance and as more information emerges from the human genome project, deeper insights will become possible into the genetics of aging. Aging, cancer, and many of the most common diseases of old age may indeed be part of a similar genetic complex, that is regulated by a surprisingly small gene set. Molecular medicine in the very near future may begin to address these diseases at the genetic level. With cellular markers for aging we may begin to develop means to modify genes in order to optimize our maximum life span and to lessen the burden of the most common diseases of old age.

Geriatrics & Aging will be at the forefront in reporting these exciting developments. I would be very interested in hearing your thoughts on whether "Aging is a Disease", please e-mail me at: geriatrics@ribosome.com.

Oncology and Aging--Bitter Truths and Misguided Paternalism

Oncology and Aging--Bitter Truths and Misguided Paternalism

Teaser: 

Shabbir M.H. Alibhai, MD, FRCP(C)

It is my pleasure to have been invited to write this editorial on the interface of oncology and aging. As a Geriatrician and a researcher in prostate cancer, this topic is near and dear to my heart. Astute readers will realize that this theme has been employed once before in Geriatrics & Aging. Clinicians will also recognize the tremendous burden that cancer in the elderly imposes--hence our decision to revisit this theme annually. In this issue we have attempted to deal with both commonly discussed tumors not focused on previously (prostate), as well as less commonly discussed malignancies (brain, lymphoma). We hope you find this issue informative.

Recently, there has been a tremendous surge in interest directed at the fields of oncology and aging, coming from a myriad of perspectives. For example, oncology training programs in the U.S. are beginning to have mandatory rotations for trainees in geriatric medicine. Whether Canadians will follow suit remains to be seen. I wish to touch further on three areas--cancer screening in the elderly, trends in treatment, and implicit values.

When we examine recommendations for cancer screening for the elderly (from such internationally respected organizations as the Canadian Task Force on Preventive Health Care), there appear to be no recommendations made (based on current evidence) to screen for any malignancy for anyone over the age of 70 to 75. Most other organizations, no matter how "evangelical", echo the CTFPHC's recommendations' principles. This is most interesting and bears further scrutiny. Why is there such consensus? Is it because cancer is uncommon in the elderly? Hardly. Is disease unlikely to be found at a curable stage? No. In general, and for most tumor types, it occurs more often than in younger patients. Is it because of the proven lack of benefit of screening? Once again, no. In most instances, there is simply a paucity of controlled clinical studies which have included patients in this age group. So what else can the CTFPHC fairly conclude? Could it be that the reasons for the recommendations (or absence thereof) have far more to do with lack of proof of efficacy than proof of lack of efficacy.

…there are countless studies demonstrating that older patients are treated less aggressively than younger patients, even with similar stage and grade of disease.

The lessons we learn from the screening recommendations can be extended to the treatment of cancer in seniors. From surgical therapy for localized prostate and lung cancer to adjuvant therapy for colorectal and breast cancer, to intensive chemotherapy for leukemia and lymphoma, there are countless studies demonstrating that older patients are treated less aggressively than younger patients, even with similar stage and grade of disease. What accounts for this disparity? Closer examination of these studies reveals two main reasons: a perception of decreased life expectancy for an older cancer victim, and an increased risk of toxicity in treating the elderly. Note that lack of efficacy is rarely an issue. Clinicians (and family members) argue that older patients are more likely to die of other causes than of their underlying malignancy. Yet the work of numerous cancer scientists in various fields, including some of my own work in prostate cancer, shows that this is often not the case, especially for higher grades of neoplasm in relatively healthy older people. Furthermore, clinicians generally fare poorly when trying to estimate life expectancy, even for dying patients in a palliative care unit (as one recent study reaffirmed). On the toxicity front, numerous studies in the last few years have supported the notion that body-weight-adjusted chemotherapy is generally well-tolerated by the elderly, often to a degree comparable with younger patients. As concerns the morbidity and mortality of surgery, carefully selected older patients have only slightly higher treatment risks than younger ones--these are nowhere near the figures that some experts have been heard quoting at the bedside. Yet misperceptions flourish.

Something obvious but heretofore unspoken needs to be said. Evidence is accumulating that the attitudes of clinicians who treat cancer are ageist; this is to say they are discriminating unfairly or without due justification against individuals on the basis of age. Implicit in this ageist bias is the value that we place on life. For example, a 50-year-old man with localized high grade prostate cancer will gain 9 years of life with surgery, while a 75-year-old man will only gain 2 years; should we treat the older man? I believe that for too long we have implicitly attached our own values to the years of life gained from intervention. If this was done systematically and openly, supported by the society at large, that would be one thing. Done haphazardly and secretly, it is far from ideal. Without question, our patients, young and old, should carefully assess the quantity and quality of life, with or without treatment, before making any decision. Unfortunately, when it comes to the elderly, it has become amply clear that they are not even being given the chance to choose for themselves.

Stem Cell Research May Offer Antidote to Aging of the Hematopoietic System

Stem Cell Research May Offer Antidote to Aging of the Hematopoietic System

Teaser: 

 

Kimby Barton, BSc, MSc
Assistant Editor, Geriatrics & Aging

The hematopoietic system is comprised of all the elements of the blood, together with the stem and progenitor cells that give rise to these elements, and these play a vital role in the functioning of a healthy person. The hematopoietic system is unusual in that most of its components have a short life span, a multiplicity of cell types are required for its normal function, and a wide dispersion of cells perform specific functions throughout the body. The short life span of many of its components renders necessary the continuous production of enormous numbers of cells. Consequently, stem and progenitor cells must be maintained in adequate numbers to meet this demand for cell production throughout a person's lifetime.

Age-related alterations have been found in almost all components of the hematopoietic system but historically it has been difficult to distinguish between changes that occur with advanced age and changes that occur as a result of an illness. This article will review some of the literature dealing with the effects of age on the hematopoietic system. Conflicting studies will leave some questions unanswered and a paucity of information in other areas suggests the need for further research.

Caring in an Aging Multicultural Society: Operating A Culturally Sensitive Practice

Caring in an Aging Multicultural Society: Operating A Culturally Sensitive Practice

Teaser: 

Gail Elliot, MA
McMaster University
Office of Gerontological Studies

Canada consists of over 100 ethnocultural groups. The 65+ age group is comprised of a population that largely identifies with an ethnic origin other than Canadian.1 Research has too often documented that the health care practices in this country are ethnocentric, focusing on westernized, scientific based practices that too often ignore the alternative methods of care and cure.2,3,4

In a multicultural country such as Canada, cultural sensitivity should be intricately woven throughout all interactions in the health and social service delivery system. Not only should cultural sensitivity be considered for the purpose of providing patient-centred care, it must also be recognized that this country as a whole has adopted statutory and constitutional policy, and regulations that are intended to place "equality for all" at the forefront of individual rights and freedoms. In fact, Canada has spent nearly thirty years developing policies that are designed to encourage "all of us to work together to build a society in which the principles of multiculturalism are fully realized in practice.

Shrinkage, Neuron and Synapse Loss: Aging Takes its Toll on the Brain

Shrinkage, Neuron and Synapse Loss: Aging Takes its Toll on the Brain

Teaser: 

Rhonda Witte, BSc

The process of aging is familiar to every individual. Yet, despite this familiarity, it remains one of the greatest biological mysteries. We embark on the aging journey from the very moment we are born and proceed passively until our deaths. It is a concept that some find difficult to comprehend, perhaps because it is seemingly inevitable--beyond one's control.

A multitude of theories has been proposed regarding the aging process. The question "Why do we age?" has sparked interest in many research disciplines. Of particular interest are the neurological aspects of aging. Numerous examinations of the aging brain have been performed, particularly those concerning the neurodegenerative diseases of the elderly. Interestingly, studies using animal models have suggested that estrogen replacement therapy may have a role in both the treatment and prevention of dementia by assisting the regeneration and preservation of neuronal structures.1 Close attention has also been given to the "normal" aging brain and the events that occur over a lifetime.

Along with the heart and striated muscle, the brain is the oldest part of the mammalian body. The neurons of the brain are postmitotic once differentiated and are unable to renew themselves. Thus, the brain is highly susceptible to any cellular damage that may occur with age.