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Mitochondrial microheteroplasmy and a theory of aging and age-related disease

Rafal M Smigrodzki1, Shaharyar M Khan

  • 1Gencia Corporation, Charlottesville, Virginia 22903, USA. rafal@genciabiotech.com

Rejuvenation Research
|September 8, 2005
PubMed

Insights

Mitochondrial microheteroplasmy, the presence of numerous low-abundance mutations, is proposed as a key driver of aging. This widespread mutational burden in mitochondrial genomes explains age-associated diseases and their progressive nature.

Area of Science:

  • Mitochondrial biology
  • Aging research
  • Genetics

Background:

  • Mitochondrial mutations accumulate with age.
  • Mitochondrial microheteroplasmy involves hundreds of mutations, each at low abundance (1-2%).
  • Despite low individual mutation levels, most adult mitochondrial genomes are affected.

Purpose of the Study:

  • To identify the principal component of aging.
  • To investigate mitochondrial microheteroplasmy as a candidate for aging.
  • To explain the pathomechanism of age-associated diseases with mitochondrial involvement.

Main Methods:

  • Analysis of mitochondrial mutation burden.
  • Postulation of microheteroplasmy's role in aging and disease.
  • Reconciliation of disease models with genetic properties of microheteroplasmy.

Main Results:

  • Mitochondrial microheteroplasmy is present in the vast majority of adult mitochondrial genomes.
  • This mutational burden includes inherited, de novo, and somatic mutations.
  • Microheteroplasmy can explain the pathomechanism of age-associated diseases like diabetes, cardiovascular disease, Parkinson's, Alzheimer's, and cancer.

Conclusions:

  • Mitochondrial microheteroplasmy is a strong candidate for the principal component of aging.
  • It explains the delayed and progressive course of several age-associated diseases.
  • It reconciles findings from various disease models with observed inheritance patterns.

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