10.5 未来之路和基本概念

We live in a time in which a radical change in the delivery of health care has begun. The era of precision medicine brings an end to the disease-centered medical model that has, for 100 years, placed prime importance on management of disease. Management of disease was based, in large part, on how the “average person” should respond to any given treatment—that is, population-based medicine. The disease-centered medical model is being replaced with a style of health care that emphasizes the medical needs of the individual, not the average person. Treatments and therapies are being designed to address each individual's unique genome as well as one's vision of what it means to be healthy.

The individualization of medicine also necessitates that every individual be an active and informed participant in his or her health-care options, including the incorporation of preventive measures (see Box 2.2). In regard to aging, information on how to slow the rate of aging and reduce the risk of chronic disease exists. There can no longer be any question as to the importance and effectiveness of exercise and maintaining an appropriate calorie intake in the prevention of chronic disease and slowing the rate of aging. However, that information remains fragmented and extremely generalized, factors that limit the inclusion of physical exercise and diet therapies in precision medicine. Thus, the road ahead, at least in terms of aging, will be the development of the ways in which the physician can incorporate exercise and diet instructions tailored to each individual. Once established, the health-care professional can prescribe, much in the same way drugs are now prescribed, diet and exercise recommendations uniquely suited to each patient.

The first steps in developing mechanisms that allow for the individualization of diet and exercise therapies and preventative measures are now taking place. In 2015, the National Institutes of Health (NIH) provided $170 million in research funds for a program named the Molecular Transducers of Physical Exercise in Humans. It is hoped that results of this research will lead to a comprehensive map of the molecular changes that occur in response to exercise. According to NIH Director Francis Collins, “The development of a so-called molecular map of circulating signals produced by physical exercise will allow us to discover, at a fundamental level, how physical exercise affects our health. This knowledge should allow researchers and doctors to develop individually targeted exercise recommendations and better help those who are unable to exercise” (2016). Precision medicine applied to the rate of aging and prevention of chronic disease has begun.

ESSENTIAL CONCEPTS

• Aging cannot be modulated, because the laws of thermodynamics are universal and cannot be modified.
• Although aging cannot be modulated, the rate of aging can. To modulate the rate of aging, biogerontologists must begin to ask, “Why do we live?” rather than “Why do we die?”
• A genomics approach is required to determine which genes are most susceptible to the second law of thermodynamics.
• Calorie restriction without malnutrition extends mean and maximum life span in every nongenetically modified species tested.
• Altering the macronutrient composition of the diet or increasing its vitamin and mineral content has little effect on life span in calorie-restricted animals.
• Biogerontologists are using simple organisms such as yeast, worms, and flies to investigate the mechanisms underlying life extension through calorie restriction.
• Preliminary results suggest that rhesus macaques that are calorie-restricted to 30% of ad libitum intake seem to have a mean life span slightly greater than that of monkeys fed ad libitum; maximum life span may not be different. Potential differences are small compared with those observed in other species.
• Calorie-restricted monkeys have lower rates of age-related diseases than ad libitum–fed animals.
• The effectiveness of calorie restriction in humans remains unknown and controversial.
• The lower risk of age-related disease achieved through physical exercise has the potential to increase mean life span; exercise does not increase maximum life span.
• The primary effect of physical exercise in slowing the rate of aging is to increase reserve capacity.
• The aging population of the future will be characterized by extended youth and the compression of morbidity.
• The growing aged population and the coming of precision medicine require that the definition of health must include language recognizing the right of the individual to define his or her own health status.
• It is likely that a definition of health during the era of precision medicine will focus on the ability to adapt and manage any limitations to daily living.
• Research using the successful aging paradigm found great heterogeneity in time-dependent function loss and incidence of chronic disease.
• The observation of a significant population of high-functioning older individuals brought an end to the research paradigm suggesting that old age was a time of disease, disability, and disengagement from life. In its place arose a research paradigm that focuses on identifying the factor(s) that can be targeted to alter time-dependent functional loss and the development of chronic disease.

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