What is your proteome? In short, it is the list of all the proteins built within your body and their abundance - a parts catalog for your biological machinery. Analysis of even modest fractions of the proteome has only recently become practical, but it is potentially a good way to measure the complexity of repairing and reversing aging, or gain insight into which contributing mechanisms of aging are the most important. Aging is no more than change: damaged proteins, unwanted molecules, things in the wrong place at the molecular level - which leads to malfunction and failure in the large-scale organs and processes of the body.
The good news for today is that a comparison of young and old proteomes in mice shows that there is little change with aging. This is a positive result for the future of longevity science, because it means researchers can rapidly follow up on the few changes that were identified. The opposite result - many changes, as is the case for gene expression - would have been rather discouraging: a sign that matters are very complex in yet another area of the biology of aging, and that much work would have to take place in order to understand the relevance of the data.
The biological process of aging is believed to be the result of an accumulation of cellular damage to biomolecules. While there are numerous studies addressing mutation frequencies, morphological or transcriptional changes in aging mammalian tissues, few have measured global changes at the protein level. Here, we present an in depth proteomic analysis of three brain regions as well as heart and kidney in mice aged 5 or 26 months.
In frontal cortex and hippocampal regions of the brain, more than 4,200 proteins were quantitatively compared between age groups. Proteome differences between individual mice were observable within and between age groups. However, mean protein abundance changes of more than two-fold between young and old mice were detected in less than 1% of all proteins and very few of these were statistically significant. Similar outcomes were obtained when comparing cerebellum, heart and kidney between age groups. Thus, unexpectedly, our results indicate that aging-related effects on the tissue proteome composition at the bulk level are only minor and that protein homeostasis remains functional up to a relatively high age.
It is unexpected, given the gene expression findings to date - but welcome. I look forward to seeing the results from human studies. Given the free-falling cost of bioinformatics, and commensurate improvement in the technology, comparing proteomes in young and old people will be a graduate student project within a handful of years.