This chapter addresses the following Geriatric Fellowship Curriculum Milestone: #8
Describe how biological aging induces progressive functional decline and loss of homeostatic capacity.
Understand how diet, genetics, and pharmacologic intervention can affect the rate of aging.
Explain how genetic or pharmacologic interventions affect intracellular signaling pathways such as insulin/insulin-like growth factor (IGF), mTOR, and sirtuins to extend mammalian lifespan.
Key Clinical Points
Biological aging predisposes older individuals to disease and increased mortality risk.
Dietary restriction (DR) extends lifespan and promotes late life health in diverse taxa, including mammals.
Interventions that slow the aging rate also delay or even prevent multiple age-associated pathologies simultaneously, such as cancer, neurodegeneration, metabolic syndrome, renal dysfunction, and many others.
Aging is the process that converts young adults, most of them healthy and in no need of assistance from physicians, into older adults whose deteriorating physiologic fitness leads to progressively increasing risks of illness and death. The effects of aging are so familiar to health professionals and aging adults that they are viewed by both parties as immutable, taken for granted, an arena in which diseases and their treatments take place, but not subject to intervention or modulation. The major discovery in biogerontology, gradually emerging from decades of work in animal model systems, is that this old-fashioned viewpoint is wrong, and that the aging process can be delayed or decelerated in mammals, built very much like human beings, by simple manipulations of nutritional signals and genetic circuits similar to those already well-documented in people. It is now routine to extend lifespan, in rats and mice, by about 40%. This effect is, remarkably, 10 times greater than the increase in active life expectancy that would ensue from a complete elimination of all neoplastic illnesses, or all heart attacks, in a human population. Work in mice is also just starting to show that drugs, including some already in clinical use, can produce meaningful increases in mouse lifespan. As importantly, genetic and pharmacologic interventions that increase longevity typically delay or even prevent many classes of age-associated diseases, such as cancer, metabolic decline, and neurodegeneration. It thus seems likely that a more detailed understanding of the factors that determine aging and the processes by which aging increases the risk of such a wide range of lethal and nonlethal illnesses and disabilities could, in the foreseeable future, have a profound impact on human health and preventive medicine.
Aging is a mystery, in the same sense that infectious disease was once a mystery, and consciousness still is: an area of investigation in which well-informed researchers cannot be certain that they have selected a line of investigation bound to be productive. For a long time, most published papers in biogerontology journals consisted of descriptions of the ways in which young mice, rats, or people differed from older ones. This descriptive era has been superseded by one focused on specific molecular ...