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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 at least four common environmental factors known to damage biological macromolecules such as proteins and DNA.

  • Describe 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 and name 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.

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

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

  • Explain the evolutionary implications of a genetically encoded lifespan.


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, loss of residual “baby fat,” maturation of the gonads and brain tissue, and the emergence of secondary sex characteristics—that transform the dependent child into a strong, 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 or three decades.

Barring fatal illness or injury, the onset of the final stage of life, old age, is signaled by a resurgence of physical and physiological change. Hair begins to noticeably thin, turning white or gray as it loses its pigmentation. Skin loses its suppleness and accumulates blemishes. Individuals appear to shrink as both muscle and bone mass are progressively lost. Attention span and recall decline. Eventually, inevitably, life itself comes to an end as one or more 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 physiological events associated with aging. Slowing or stopping some of the degenerative processes that cause or accompany aging can render the last stage of life much more vital, productive, and fulfilling. Co-opting the factors responsible for triggering cell death may enable physicians to selectively destroy harmful tissues and cells such as tumors, polyps, and cysts without collateral damage to healthy tissues.



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