Bioremediation meets biomedicine: therapeutic translation of microbial catabolism to the lysosome.
Lysosomal degradation of damaged macromolecules is imperfect: many cell types accumulate lysosomal aggregates with age. Some such deposits are known, or are strongly suspected, to cause age-related disorders such as atherosclerosis and neurodegeration. It is possible that they also influence the rate of aging in general. Lysosomal degradation involves extensive cooperation between the participating enzymes: each generates a substrate for others until breakdown of the target material to recyclable units (such as amino acids) is complete. Hence, the age-related accumulation of lysosomal aggregates might be markedly retarded, or even reversed, by introducing just a few bacterial or fungal enzymes -'xenohydrolases' - that can degrade molecules that our natural machinery cannot. This article examines the feasibility and biomedical potential of such lysosomal enhancement as an approach to retarding or treating age-related physiological decline and disease.
de Grey
Aubrey D N J
AD
Dept of Genetics, University of Cambridge, UK. ag24@gen.cam.ac.uk
D000375:Aging / Q000187:drug effects* / Q000502:physiology*; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D001673:Biodegradation, Environmental; D005658:Fungi / Q000201:enzymology / Q000235:genetics; D006801:Humans; D006867:Hydrolases / Q000378:metabolism / Q000627:therapeutic use*; D016464:Lysosomal Storage Diseases / Q000503:physiopathology* / Q000628:therapy*; D008247:Lysosomes / Q000502:physiology*; D014170:Transformation, Genetic
D006867:Hydrolases