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After studying this chapter, you should be able to:

  • Describe the essential features of wear and tear theories of aging.

  • List four or more common environmental constituents known to damage biologic macromolecules such as proteins and DNA.

  • Explain why nucleotide bases are especially vulnerable to damage.

  • Describe the most physiologically important difference between mitochondrial and nuclear genomes.

  • Describe the oxidative theory of aging.

  • List the primary sources of reactive oxygen species (ROS) in humans.

  • Describe three mechanisms by which cells prevent or repair damage inflicted by ROS.

  • Describe the basic tenets of metabolic theories of aging.

  • Explain the mechanism of the telomere “countdown clock.”

  • Outline our current understanding of the genetic contribution to aging.

  • Explain the benefits of model organisms to biomedical research.


Consider the various stages in the lifespan of Homo sapiens. Infancy and childhood are characterized by continual growth in height and body mass. Basic motor and intellectual skills develop: walking, language, etc. Infancy and childhood also represent a period of vulnerability wherein a youngster is dependent on adults for water, food, shelter, protection, and instruction. Adolescence witnesses a final burst of growth in the body’s skeletal framework. More importantly, a series of dramatic developmental changes occur—an accumulation of muscle mass, maturation of the gonads and brain, and the emergence of secondary sex characteristics—that transform a child into an independent and reproductively capable adult. Adulthood, the longest stage, is a period devoid of dramatic physical growth or developmental change. With the notable exception of pregnancy in females, it is not unusual for adults to maintain the same body weight, overall appearance, and general level of activity for two decades or more.

Barring fatal illness or injury, the onset of the final stage of life, old age, is signaled by a resurgence of physical and physiologic change. Muscle and bone mass progressively decrease. Hair begins to thin and lose its pigmentation. Skin loses its suppleness and accumulates blemishes. Attention span and recall decline. Eventually, inevitably, life itself comes to an end as essential bodily functions decline.

Understanding the underlying causes and instigating triggers of aging and the changes that accompany it is of great biomedical importance. Hutchison-Gilford, Werner, and Down syndrome are three human genetic diseases whose pathologies include an acceleration of many of the physiologic events associated with aging. Slowing or preventing some of the degenerative processes that cause or accompany aging can render the later stages of life more vital, productive, and fulfilling. Coopting the factors responsible for triggering cell death may enable physicians to selectively destroy harmful tumors, polyps, and cysts.


From Paleolithic to Medieval times the average life expectancy of a newborn baby oscillated a the range of 25 to 35 years. Beginning with the Renaissance, however, this number gradually increased such that, by the beginning of ...

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