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Theories of Aging

The best available research (2, 3) divides theories of aging into four categories:

  • Molecular Theories (Codon restriction, Error catastrophe, Somatic mutation, Dysdifferentiation, Gene regulation)
  • Cellular Theories (Wear and tear, Free radical, Apoptosis, Senescence)
  • System Theories (Rate-of-living, Neuroendocrine, Immunologic)
  • Evolutionary Theories (Disposable Soma, Antagonistic Pleiotropy, Mutation Accumulation)

Acceptance (and groupings) of the theories above (as well as each theory's significance in the overall bio-molecular aging picture) varies among scientist. The Free-Radical theory has almost universal acceptance.

Here are some of the theories above, meshed into derivative theories:

  • Telomere shortening/loss (replicative senescence)
  • Macromolecular oxidative stress and damage: such as from free radicals
  • Glycation: tightly-woven matrix of glucose and proteins leading to compromised tissue elasticity
  • Dysdifferentiation (e.g. cancer; "Gradual accumulation of random molecular damage impairs regulation of gene expression"(2) and "... instability of the differentiated state of cells and how active oxygen species may interact with the genetic apparatus of cells, leading to improper gene regulation."(1))
  • rDNA: "Codon restriction - Fidelity/accuracy of mRNA translation is impaired due to inability to decode codons in mRNA" (2)
  • DNA damage and mutations: such as from free radicals
  • Membrane dysfunction: such as resulting from the accumulation of free-radical damage
  • Compromised protein synthesis: such as from free radicals
  • Disturbances in calcium metabolism: "Aging and diseases are associated with blunting of the calcium concentration gradient, due to calcium deficiency and consequent secondary hyperparathyroidism." (4)
  • Autoimmunity (organismal immunity "turning on itself")

References and Resources:

1. Dysdifferentiation hypothesis of aging and cancer: a comparison with the membrane hypothesis of aging. Zs-Nagy I, Cutler RG, Semsei I. PMID: 3288042

2. Theories of Aging MCB135k, 2/10/03: http://mcb.berkeley.edu/courses/mcb135k/BrianOutline.html

3. Aging: A Biological Perspective. Arking, Robert. American Scientist. November-December 2003. Volume 91.

4. Aging and calcium metabolism. Fujita T. PMID: 2119658

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