This chapter addresses the following Geriatric Fellowship Curriculum Milestone: #8
To provide the genetic background for diseases associated with aging
To review the current available genetic tools and properties to study the complex phenotypes of aging
To appreciate the important role played by genes in age-associated diseases
Key Clinical Points
Genetic screening for genetic predisposition is justified if the disease (ie, age-associated diseases) is clearly clinically defined. The greater the differences between healthy subjects and disease carriers, the greater is the chance to find a genetic link.
Genetic tests for age-associated diseases are important, especially in families with history of such diseases.
Carriers of a mutation associated with disease may be at higher risk to develop the disease; however, many carriers may not ever develop the disease.
Positive genetic test results may provoke anxiety and distress. Nevertheless, they allow positive action such as early treatment and preclinical screening to reduce risk.
Aging can be characterized as a multisystem decline in healthy performance with time. This phenomenon has been observed across the animal kingdom, and analogous processes occur in the plant kingdom. Do we start aging at the moment we stop growing (at about 25 years old), or is there a period of maintenance/latency? In females, a period of maintenance appears to exist until the menopause (which is followed by a steep decline in some aspects of health). In males physical attrition may start earlier, is more gradual, and lasts longer. The dramatic increased prevalence of common diseases with age is discussed in detail in Chapter 5. For most diseases, there is a low incidence between 20 and 50 years of age, and a manifold increase afterward. Such events suggest that during the adult period there are enough biological resources (the biological system is still “in shape” and is moving from growing to maintenance) to buffer deleterious biological effects of preaging processes and thus maintain age-associated diseases on a “low flame.” When these resources are exhausted, the body can no longer cope with the harmful aging processes and thus serves as a Petri dish for the occurrence of diseases.
The questions that we ask are (a) Does the profound multisystem performance decline with age promote disease occurrence? or (b) Is genetic predisposition the main cause of the decline? or (c) Does a combination of the two enhance the accumulation and progression of diseases?
Failure of body systems with age contributes to frailty (see Chapter 46) which can result in more severe diseases leading to death. Our first question is supported by this example. However, in this chapter we will list a group of age-associated diseases and organ failures that are a result of an increased prevalence of deleterious genetic predispositions with age and the mechanisms of their effects. These examples support our second question. That said, we presume ...