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The dramatic increase in the population of older people is one of the most significant changes in human history. In the past few years, the number of people over the age of 65 exceeded that of children under the age of 5 for the first time, and by 2050, older people will likely outnumber children under the age of 14 (Fig. 476-1).

FIGURE 476-1

Globally, the people over the age of 65 years now exceed children under the age of 5 years.

Old age is associated with an inexorable increase in the incidence of chronic disease, multimorbidity, and mortality. In developed nations, older people are living longer due to advances in medical care and technology, but at the cost of longer periods of disability and the iatrogenic burdens associated with intensive medical care of multiple diseases, such as polypharmacy. Establishing the relationship between aging and disease, particularly noncommunicable disease, is one of the most important goals for biomedical research. Recent studies in animal models have confirmed that the aging process is malleable, raising the prospect that medical care in the future may treat aging itself rather than multiple age-related diseases.

Aging is usually defined as a progressive process associated with deterioration in structure and function, leading to increased susceptibility to disease and mortality, and is often associated with impaired reproductive capacity. There are statistical, biological, and phenotypic components to aging. From the statistical perspective, aging in humans is associated with an exponential risk of mortality with time (Gompertz law of mortality). The biological mechanisms of aging are encompassed by the “hallmarks of aging,” which describe the key cellular mechanisms underpinning aging. The phenotypic components of aging include chronic diseases and age-related syndromes that are often the target of medical interventions (Fig. 476-2).

FIGURE 476-2

Definitions of aging include (A) a biological component, which is encapsulated by the nine hallmarks of aging, (B) a phenotypic component which includes many chronic non-communicable diseases, and (C) a statistical component which in most species is an exponential (Gompertz) increase in the risk of mortality with age.

A fundamental feature of aging is that for any quantitative factor that can be measured in a population, the range of variability of values for that factor increases with age.


Evolutionary theories of aging attempt to explain why aging, which impairs health and survival, has evolved, and why there is so much variability in life span across taxa. Most theories are based on the concept that in the wild, age-related mortality is secondary to extrinsic causes, such as predation, injury, and infection, and evolutionary selection pressure is generated by early life survival and reproductive success. Therefore, selection pressure to maintain ...

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