8.9 未来之路和基本概念

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8.9 未来之路和基本概念

We have emphasized throughout this text that the life sciences, including biogerontology, are moving from a largely observational science to a provable quantitative science. The time-dependent changes in the physiological systems described here provide an excellent example of why a change in the research paradigm has great importance to biogerontology. Recall that biogerontology has relied on the power of reductionism to explain the cellular and molecular mechanisms of aging. The path of discovery in the cellular and molecular mechanisms of aging began with the observations of time-dependent decline in physiological systems. It was generally assumed that identifying the underlying mechanisms for the observed time-dependent decline in individual physiological function would eventually lead to “treatments” and “cures” for aging. This assumption arose from the fact that the reductive method was and continues to be phenomenally successful at curing infectious disease and discovering treatments that lessen the impact of chronic disease.

While much has been learned about the cellular and molecular mechanisms of aging, “treatments” and “cures” have not been realized. The lack of treatments for aging reflects, in large part, the fact that aging is a complex trait, a trait that emerges from the interactions among multiple mechanisms or systems. Complex traits cannot easily be studied through the disease-centered model of research with its exclusive reliance on reductionism. Finding a treatment for aging by investigating the mechanisms of time-dependent functional loss in a single physiological system will not be successful. Treatments aimed specifically at aging will, most likely, be discovered through a more holistic and quantitative approach.

This chapter has provided evidence that using the holistic approach to finding treatments for time-dependent functional loss represents the future of biogerontology research. To this end, we described research showing that old rats exposed to the biological environment of a young animal, parabiosis, have increased function in their muscle repair mechanisms (see the chapter; “Satellite cell function decreases over time”). The parabiosis method has also been used to show that the young biological environment improves function in the immune systems of old animals. The improvement of function in these two independent physiological systems provides proof of principle that a systemic factor can impact multiple physiological systems simultaneously as well as an organism's overall rate of aging. We suspect that the future of biogerontological research will include a greater reliance on the holistic approach, including the in silico models that are important to quantitative biology. In the next chapter, we describe a recently funded large-scale research program intended to evaluate the mechanism by which regular exercise slows the rate of aging through its effect on multiple physiological systems.

ESSENTIAL CONCEPTS

  • Once humans have attained full growth and development (i.e., maturity), changes in body weight reflect changes in the amount of fat stores.
  • Energy balance—energy intake minus energy expenditure—can be used to calculate changes in fat storage.
  • Energy intake can be determined by calculating the amounts of fat, protein, and carbohydrate we eat. Energy expenditure is calculated by measuring respiratory gases; total energy expenditure equals resting energy expenditure plus physical activity plus diet-induced thermogenesis.
  • Body weight increases, on average, by approximately 15% between the ages of 20 and 70 years.
  • Near the end of life, body weight declines, and this reflects losses in muscle and adipose tissue mass. Decrease in food intake parallels the end-of-life decline in body weight and can lead to a clinical condition known as anorexia of aging.
  • Longitudinal studies show that decline in muscle mass during maturity, known as aging muscle atrophy, occurs at a rate of about 8% per decade in sedentary men and about 5% per decade in sedentary women. A structured and regular exercise routine throughout life results in muscle mass losses that are approximately half that observed in sedentary individuals. Losses in muscle strength and power during aging muscle atrophy are about the same as losses in mass.
  • Aging muscle atrophy is the result of both muscle fiber loss and cellular atrophy and has an intrinsic and extrinsic aging component. Although the intrinsic mechanism(s) underlying aging muscle atrophy remain to be elucidated, time-dependent muscle cell denervation and loss in satellite cell proliferation have been shown to correlate well with muscle fiber disfunction.
  • Skin wrinkles are caused by three time-dependent changes: (1) loss in number and function of skin cells; (2) loss of subcutaneous fat; and (3) increase in nonenzymatic cross-links in collagen. The loss in subcutaneous fat in the face, arms, and legs causes irregularities that are covered by a thinner, relatively inelastic epidermis, and thus the creation of wrinkles.
  • The majority of skin aging results from overexposure to UV light.
  • The time-dependent decline in hearing, known as presbycusis, results from alterations in the inner ear, but the reasons for these changes are unknown.
  • Most individuals over the age of 50 years have alterations in the optics portion of the eye that affect the ability to focus on close objects, a condition known as presbyopia.
  • Presbyopia seems to be primarily caused by two factors: the lens's inability to repair damage and excess nonenzymatic cross-linking.
  • Time-dependent changes in taste buds and olfactory centers are minimal.
  • The incidence of atrophic gastritis increases with aging and is the result of infection by H. pylori.
  • Time-dependent changes in the small intestine are minimal and seem not to significantly disrupt the absorption of most nutrients.
  • Renal blood flow decreases with age in terms of both total amount and percentage of cardiac output.
  • Determining time-dependent loss in the human immune system is challenging because the acquired immune system develops mainly during the individual's early development period and depends to a great extent on his or her interaction with the environment.
  • Time-dependent functional loss in the innate immune system reflects losses in the phagocytotic function of neutrophils and macrophages and a decrease in cytokine and chemokine release.
  • Aging results in significant atrophy of the thymus gland and thus a reduced production of naive T cells.
  • The number of peripheral B cells declines with age, reflecting changes in the B-cell progenitor pathway in the bone marrow.
  • Women and men experience significant time-dependent changes in their reproductive processes. Female fertility ends with the cessation of menses and the onset of menopause at about 50–60 years of age. Ovarian production of sex-linked hormones drops dramatically. Male fertility and production of sex hormones decline with age. The genetic quality of sperm also seems to decline with advanced age, resulting in an increased risk for genetic problems in offspring.

 

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