Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases

Ageing Res Rev. 2005 Aug;4(3):315-38. doi: 10.1016/j.arr.2005.03.008.

Abstract

Several major diseases of old age, including atherosclerosis, macular degeneration and neurodegenerative diseases are associated with the intracellular accumulation of substances that impair cellular function and viability. Moreover, the accumulation of lipofuscin, a substance that may have similarly deleterious effects, is one of the most universal markers of aging in postmitotic cells. Reversing this accumulation may thus be valuable, but has proven challenging, doubtless because substances resistant to cellular catabolism are inherently hard to degrade. We suggest a radically new approach: augmenting humans' natural catabolic machinery with microbial enzymes. Many recalcitrant organic molecules are naturally degraded in the soil. Since the soil in certain environments - graveyards, for example - is enriched in human remains but does not accumulate these substances, it presumably harbours microbes that degrade them. The enzymes responsible could be identified and engineered to metabolise these substances in vivo. Here, we survey a range of such substances, their putative roles in age-related diseases and the possible benefits of their removal. We discuss how microbes capable of degrading them can be isolated, characterised and their relevant enzymes engineered for this purpose and ways to avoid potential side-effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aging / metabolism*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Bacteria / enzymology
  • Bacteria / genetics
  • Biodegradation, Environmental
  • Contraindications
  • Coronary Artery Disease / metabolism
  • DNA Fingerprinting
  • Gene Expression Profiling
  • Genetic Therapy / adverse effects
  • Genetic Therapy / trends
  • Humans
  • Lipoproteins / metabolism
  • Lysosomal Storage Diseases / genetics
  • Lysosomal Storage Diseases / metabolism*
  • Lysosomal Storage Diseases / therapy
  • Lysosomes / enzymology
  • Lysosomes / metabolism
  • Macular Degeneration / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Peptide Hydrolases / biosynthesis
  • Peptide Hydrolases / genetics*
  • Pyridinium Compounds / metabolism
  • Retinoids / metabolism
  • Soil Microbiology*
  • tau Proteins / metabolism

Substances

  • A2-E (N-retinylidene-N-retinylethanolamine)
  • Amyloid beta-Peptides
  • Lipoproteins
  • Pyridinium Compounds
  • Retinoids
  • tau Proteins
  • Peptide Hydrolases