Molecular Mechanism of Aging

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Prologue: 6 Main Causes of Aging

Introduction

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Molecular And Cellular Mechanism of Aging -- Outline

1. Damage or Error (Based) Theory of Aging
   1. Formulations of Damage/Errors/Waste Accumulation Theories
      • Wear and Tear
      • Error Catastrophe Theory of Aging
      • Waste Accumulation Theory of Aging
      • Misrepair Accumulation Theory (new theory)
   2. Individual Damage/Error Accumulation Mechanisms and Theories
      • Oxidative Damage -- Free Radical
      • Cross linking --Glycation
      • Cross linking --Methylation
      • Somatic DNA damage/mutation
      • Inaccuracy of mRNA translation
      • Mitochondrial Damage  -- Depletion of Cellular Energy
      • Chronic or Excess Inflammation Damage
   3. Molecular And Cellular Mechanism of Stress-Induced Premature Senescence (SIPS)
2. Programmed Epigenomic Theory of Aging (Genetic Based Theory of Aging)
   1. The Genetic Clock
      • Molecular Level: aging and longevity assurance genes
      • Programmed Cellular Senescence
      • Apoptosis and Aging
      • Premature Aging Genetic Diseases: Progeroid syndromes
   2. Hormonal Theory of Aging
   3. Neurological Degeneration
   4. Immune System Compromise
   5. Introduction to Evolutionary Theories of Aging and Longevity
      • The theory of programmed death by August Weismann
        • Disposable Soma Theory
      • the mutation accumulation theory of aging by Peter Medawar
      • the antagonistic pleiotropy theory of aging by George Williams
3.  Molecular Marker (Biomarker) of Cellular Senescence
   1. Replicative Senescence
      • Cell Cycle and Aging -- Hay flick's Limit
      • Telomere Shortening and Damage
   2. Lipofuscin Accumulation
   3. Membrane permeability to potassium (K+)
   4. Cellular Dysdifferentiation
   5. Cell Polarity and Aging
   6. Adult or Somatic Stem Cell Theory of Aging
4. Beyond The Molecular/Cellular Biology of Aging
   • Rate of Living Theory (Maximal Metabolism Scope Theory)
   • Reliability Theory of Aging
   • The Thermodynamic Point of view of aging - entropy: The driving Force
5. Inter-Relationships of Aging Theories

Introduction

Theories of aging fall into two groups. The programmed theories hold that aging follows a biological genetic clock, perhaps a continuation of the developmental program that regulates childhood growth and development. The damage or error theories emphasize environmental factors or random stochastic events that gradually cause our body to go wrong through progressive accumulation of environmentally triggered or random spontaneously occurred  "damages/errors" at molecular and cellular levels of vast biochemical and metabolic processes. It is now increasingly realized that the underlying mechanisms which govern aging is a complex interplay of genetic regulation and damage/waste accumulation. It has been proposed that aging is a result of accumulation of "damage/errors/faults’ at cellular and molecular level because of our body's limitation or breakdown of our internal "maintenance, repair and defense mechanism/system" while we age; and that the genetic control of longevity may work mainly by regulating such "essential mechanism of maintenance, repair and defense processes which functions to slow/block/prevent the accumulation of damage/errors while we are young. Such "essential maintenance and repair  mechanism" which decline when we aging is termed as longevity assuring maintenance and repair systems (MRS).

Based on studies of identical twins, who share the exact same set of genes, scientists now suspect that lifespan is determined by both environmental and genetic factors, with genetics accounting for up to 35 percent of this complex interaction. Figure 1 summaries each proposed theory under these 2 broad groups. Follow the link to a detailed explanation of each aging theory and its elaboration and validation by experimental evidence.

A unified theory of biological aging in terms of failure of homeodynamics comprising of MRS, and involving genes, milieu and chance, is acquiring or may acquire a definitive shape and wider acceptance in the end. Such  theory should be able to establish the basis for testing and developing effective means of intervention, prevention and modulation of aging in addition to explain all various age-related phenotypes.

Figure. Aging Theories