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

de Grey AD, Alvarez PJ, Brady RO, Cuervo AM, Jerome WG, McCarty PL, Nixon RA, Rittmann BE, Sparrow JR
Ageing Res Rev. 2005 4 (3): 315-38

PMID: 16040282 · DOI:10.1016/j.arr.2005.03.008

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.

MeSH Terms (22)

Aging Alzheimer Disease Amyloid beta-Peptides Animals Bacteria Biodegradation, Environmental Contraindications Coronary Artery Disease DNA Fingerprinting Gene Expression Profiling Genetic Therapy Humans Lipoproteins Lysosomal Storage Diseases Lysosomes Macular Degeneration Oligonucleotide Array Sequence Analysis Peptide Hydrolases Pyridinium Compounds Retinoids Soil Microbiology tau Proteins

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