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  • de Grey ADNJ. Bioremediation meets biomedicine: therapeutic translation of microbial catabolism to the lysosome. Trends Biotechnol 2002;20(11):452-455. PubMed: 12413818. Categories: LysoSENS

    Bioremediation meets biomedicine: therapeutic translation of microbial catabolism to the lysosome.

    Trends Biotechnol 2002;20(11):452-455.

    Bioremediation meets biomedicine: therapeutic translation of microbial catabolism to the lysosome.

    de Grey ADNJ.

    Abstract

    Abstract:

    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 ADNJ, Baynes JW, Berd D, Heward CB, Pawelec G, Stock G. Is human aging still mysterious enough to be left only to scientists? BioEssays 2002;24(7):667-676. PubMed: 12111727. Categories: SENS Overviews

    Is human aging still mysterious enough to be left only to scientists?

    BioEssays 2002;24(7):667-676.

    Is human aging still mysterious enough to be left only to scientists?

    de Grey ADNJ, Baynes JW, Berd D, Heward CB, Pawelec G, Stock G.

    Abstract

    Abstract:

    The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY Acad Sci 959, 452-462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it.

  • de Grey ADNJ. Mitochondrial gene therapy: an arena for the biomedical use of inteins. Trends Biotechnol 2000;18(9):394-399. PubMed: 10942964. Categories: MitoSENS

    Mitochondrial gene therapy: an arena for the biomedical use of inteins.

    Trends Biotechnol 2000;18(9):394-399.

    Mitochondrial gene therapy: an arena for the biomedical use of inteins.

    de Grey ADNJ.

    Abstract

    Abstract:

    Mitochondrial DNA (mtDNA) mutations underlie many rare diseases and might also contribute to human ageing. Gene therapy is a tempting future possibility for intervening in mitochondriopathies. Expression of the 13 mtDNA-encoded proteins from nuclear transgenes (allotopic expression) might be the most effective gene-therapy strategy. Its only confirmed difficulty is the extreme hydrophobicity of these proteins, which prevents their import into mitochondria from the cytosol. Inteins (self-splicing 'protein introns') might offer a solution to this problem: their insertion into such transgenes could greatly reduce the encoded proteins' hydrophobicity, enabling import, with post-import excision restoring the natural amino acid sequence.

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