Toxic Metabolites in the Biology of Ageing and Cancer

Toxic metabolites in our metabolism, diet and in pollution have a major impact on human health. For example, alcohol and sugar toxic metabolites contribute to global mortality, ageing, diabetes, neurodegeneration and cancer. In the past decade, there has been a transformation in our understanding of how toxic metabolites contribute to ageing and disease – where they come from, how organisms protect themselves against them, and how their accumulation can damage certain stem cells.

This Workshop will focus on the biology of toxic metabolites in the ageing process, stem cells and cancer. Specific emphasis will be placed on how metabolites that carry carbonyls (such as aldehydes and ketones) damage stem and cancer cells. A particular area will focus on endogenous aldehydes (such as acteladehyde, formaldehyde and methyl-gyoxal), the enzymes that remove them [aldehyde dehydrogenases (Aldh) and functionally related glutathione-based enzymes such as Adh5 and Glo-1/2]. Further, we will consider how human genetic variation can contribute to metabolite sensitivity, and how mutations in cancer genomes in toxic metabolism pathways can be exploited for therapy.

This Workshop is a first-in-kind that will focus on these reactive carbonyls and their role in ageing and disease. We bring together young and established investigators from basic, clinical and industry science to explore new avenues of how toxic metabolites and associated metabolising enzymes function in disease for the long-term benefit of stem-cell and cancer therapies.

An important outcome of this Workshop is to foster new collaborations and to promote the exchange of ideas on the function of ALDH and related enzymes. The investigators presented here are from a range of disciplines (basic science, clinical and industry) with diverse specialities in genetics, genomics, metabolism, chemistry, biochemistry, structural biology, cancer biology, drug development and animal models.