Aging biology and cancer
Section snippets
Normal aging
It is a central gerontologic principle that aging is not a disease. The functional declines that accompany normal aging have been well characterized,1 but under normal circumstances do not account for symptoms of disease. For example, kidney function declines with age,2 and, in fact, has proven to be a useful biological marker of aging (see below). Yet, clinical consequences of this change in renal function, in the absence of a disease or the exposure to an exogenous nephrotoxic agent, do not
Lifespan and maximum survival
From the perspective of those who study aging, there is an important distinction made between median (life expectancy) and maximum life span. Over the past several decades, with the advent of modern sanitation, refrigeration, and other public health measures including vaccination and antibiotics, there has been a dramatic increase in median survival.21 Early deaths have been diminished and more individuals are reaching old age. In the United States today, life expectancy now approaches 80 years.
Cellular versus organismal aging
There has been much written about cellular senescence and the events that lead up to cell death.28 After a finite number of divisions, normal somatic cells invariably enter a state of irreversibly arrested growth, a process termed “replicative senescence.”29 In fact, it has been proposed that escape from the regulators of senescence is the antecedent of malignant transformation. However, the role of replicative senescence as an explanation of organismal aging remains the subject of vigorous
Theories of aging
Providing a rational, unifying explanation for the aging process has been the subject of a great number of theoretical expositions. Yet, no single proposal suffices to account for the complexities observed (Table 1).
That genetic controls are involved seems obvious when one considers that lifespan is highly species specific. For example, mice generally live about 30 months and humans about 90 years. However, the aging phenomenon is not necessarily a direct consequence of primary DNA sequence.
Immunity and aging
As mentioned previously, there is a well-characterized deficit in immune function with advancing age, but the consequences are not fully established. It is apparent that otherwise healthy older individuals are more susceptible to reactivation of tuberculosis14, 15 or herpes zoster,16 and responses to vaccines, such as the commercially available and widely used influenza hemagglutinin are lower.17, 18, 19 However, it has been postulated that other age-associated diseases, such as cancer,70
Immune senescence and cancer
There is a commonly held notion that immune senescence is in some way related to the observed increased rate of cancer with advancing age.71 However, despite the appeal of such an hypothesis, scientific support has been limited and the topic remains controversial.87, 88 It is difficult to deny that profoundly immunodeficient animals or humans are subject to a more frequent occurrence of malignant disease, and it would stand to reason that others with less severe immunodeficiency would also be
Explanations for the increased incidence of cancer with age
Carcinogenesis is a multistage process involving serial alterations of cellular genes. These include oncogenes and antiproliferative genes (antioncogenes), which modulate cell proliferation, and genes that prevent apoptosis (programmed cell death). It is now understood that oncogenes encode proteins with a myriad of functions including growth factors, growth factor receptors, enzymes involved in the transduction of proliferative signals, DNA synthesis, and replication.91 Similarly,
Explanations for the changes in tumor progression observed with advancing age
There has been a long-held but incompletely documented clinical notion that cancers in older people are less aggressive (Table 3). However, epidemiologic data from tumor registries or large clinical trials have not been supportive. This may be because this type of data is confounded by special problems common to geriatric populations (eg, comorbidity, “poly-pharmacy,” physician or family bias regarding diagnosis and treatment in the elderly, and age-associated life stresses) and these factors
Conclusions
It has been said that all medical oncologists, with the exception of those who restrict their practice to pediatric patients, are “geriatric oncologists.” This is, of course, because the average age of cancer is in excess of 65 years and the median age of most common adult tumors approaches 70 years. Similarly, scientists studying the mechanisms of cancer development and growth are uncovering and elucidating some of the basic molecular and cellular processes of aging. These include the controls
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