As cells age, their protein composition changes. Two recent papers address these changes: the first addresses the proteome of colon epithelia, and the second focuses on a specific chemical modification in the proteins of the cerebellum.
Li et al. perform a comprehensive analysis of the colon epithelial proteome over the course of aging. The approach is intellectually straightforward with few surprises, but it’s technically sound, and I think it’s important for biogerontologists to appreciate how far proteomic technology has come — the approach used by these authors could be applied to any system of interest, comparing the old and young states and allowing us to learn about the mechanisms of age-related change in our favorite tissues:
In order to screen the aging related proteins in human normal colon epithelia, the comparative proteomics analysis was applied to get the two-dimensional electrophoresis (2-DE) profiles with high resolution and reproducibility from normal colon epithelial tissues of young and aged people. Differential proteins between the colon epithelia of two age groups were found with PDQuest software. The thirty five differential protein-spots were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and database searching. … The identified differential proteins appear to be involved in metabolism, energy generation, chaperone, antioxidation, signal transduction, protein folding and apoptosis. The data will help to understand the molecular mechanisms of human colon epithelial aging.
The second paper, also a good example of the best technology and technique currently available, focuses not on differential protein expression but rather on differences in the chemical alteration of cellular protein. The specific alteration of interest here is nitration, a marker of oxidative stress. Gokulrangan et al.:
3-Nitrotyrosine (3-NT) is a useful biomarker of increasing oxidative stress and protein nitration during biological aging. The proteomic analysis of cerebellar homogenate from Fisher 344/Brown Norway (BN/F1) rats shows an age-dependent increase in protein nitration … When proteins were separated by solution isoelectrofocusing and analyzed by NSI MS/MS, we obtained MS/MS spectra of 3-NT containing peptides of four proteins – similar to ryanodine receptor 3, low density lipoprotein related receptor 2, similar to nebulin-related anchoring protein isoform C and 2,3 cyclic nucleotide 3-phosphodiesterase. Although the functional consequences of protein nitration for these targets are not yet known, our proteomic experiments serve as a first screen for the more targeted analysis of nitrated proteins from aging cerebellum for functional characterization.
Studies of this latter kind are an important complement to the sort represented by the former kind: Covalent modifications such as nitration (and oxidation, and glycation, and ubiquitination, and sumoylation, and…) can dramatically alter protein function, but they are not encoded in the genome; hence this information is lost in a simple enumeration of the identities and abundances of every protein in the cell. In order to understand the peculiarities of aging cells’ behavior, we must learn not only about their gene expression and proteome but also the condition in which the macromolecules find themselves at any given point in time.
Ouroboros 