Biomarkers of ageing
One of the more obvious uses of ProQuant™ is to look for biomarkers of disease. We used ProQuant™ to investigate potential biomarkers of ageing, using serum samples from subjects of different ages. Across the 300 proteins measured none were found to be associated with age after correction for multiple testing.
ProQuant™ doesn’t stop there, however, so we took the same data and interrogated it more deeply. We found a strong association between age and acetaldehyde modification of proteins, but found that to be a confounding influence of alcohol, which was being enjoyed more by our older subjects!
More interestingly, we also found a strong association between age and the deamidation of asparagine residues on serum proteins, which is to the best of our knowledge a novel insight into ageing. It has been known for decades that long-lived proteins (such as crystallins in the eye and other extracellular matrix proteins) show greater deamidation in older proteins, and this has also been shown to occur in vitro. This is an unexpected observation in serum proteins, however, where proteins typically have a much shorter half-life. Indeed, the deamidation may be indicative not of increased rate of deamidation but in an extension of the protein half-lives. Or, perhaps more interestingly, is there something else in the samples from older subjects that has led to more deamidation occurring ex vivo? Regardless, it is due to the power of ProQuant™ that such subtle differences across multiple proteins can be detected.
Finally, we find one further age-related PTM which we are currently investigating further. This may prove particularly exciting but unfortunately we cannot share details publicly yet.
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