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Genomics and Ageing Well

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BRADFORD HILL SEMINAR

Professor Carol Brayne, Director of the Cambridge Institute of Public Health, will introduce David Melzer. This talk will focus on recent progress in identifying common genetic variants and genomic markers associated with ageing well. A majority of chronic disease is strongly age related, but mechanisms have been poorly understood. There is increasing evidence from laboratory models that specific pathways underlie much age related disease. There are two robust mouse models of controlling and even reversing ageing changes. Translating these findings to help humans age well is now a key challenge.

Genome wide association studies of SNPs in age related diseases have identified many relevant variants, but studies of long lived individuals or their offspring have thus far been less productive. Transcriptome wide and methylation array studies in humans are providing new insights into age related mechanisms in humans. Recent larger scale human studies of genome wide expression (notably from the InCHIANTI aging study) have identified changes in splicing, the ‘fine tuning’ of protein sequences, as a potentially important factor in decline of cellular function with advancing age. Studies of expression associations with muscle strength have shown striking concordance with a mouse model of muscle repair. A similar study of expression and cognitive decline in humans identified a gene (CCR2) knocked out in a mouse model of beta-amyloid phagocytosis. Recent explorations of age related inflammatory states will be described, illustrating some of the pitfalls of transcriptomic studies in people. The presentation will conclude with a discussion of the emerging genomic biomarkers of human ageing.

This talk is part of the Bradford Hill seminars at the Cambridge Institute of Public Health series.

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