A review of aging proteomics mapped protein markers from different systems onto shared biological processes
A review of aging proteomics mapped protein markers from different systems onto shared biological processes
On 14 August, the authors of an open-access review brought together data on age-related changes in blood proteins. They propose assessing the overall profile first, then comparing it with markers from specific organs and the results of routine tests.
Protein clocks estimate biological age from the composition of plasma, the liquid component of blood. This age indicates the age group whose profiles most closely resemble the profile being tested. In a 2019 study, researchers measured about 2 925 proteins in 4 263 people aged 18 to 95 and found nonlinear age-related shifts at approximately 34, 60, and 78 years.
A single numerical measure combines traces of different processes. Five epigenetic clocks calculated from the same blood samples were associated with different patterns of gene activity. A protein profile must likewise be interpreted in light of both the biological process and the measurement method that produced the observed signal.
The review authors organized recurring signals into four groups: inflammation and immune response; metabolic and mitochondrial stress, meaning disruptions in metabolism and cellular energy production; remodeling of the extracellular matrix, the protein framework surrounding cells; and signs of neural tissue damage accompanied by activation of glia, the supporting cells of the nervous system. The same types of signals appear in several body systems.
A general measure that combines traces of different processes reflects the overall burden on the body. To identify the organ with impaired function, the authors propose adding organ-specific marker panels, imaging, and routine clinical tests.
The meaning of a result also depends on the measurement method. Olink detects a predefined target using a pair of antibodies, while SomaScan uses aptamers, short DNA molecules that bind to proteins; both platforms produce a relative binding signal. After proteins have been digested, mass spectrometry measures their short fragments, called peptides, and determines their sequences. Oxidation, the attachment of sugars, or cleavage can alter a protein's structure and affect its binding to a reagent. A shift in the signal may therefore reflect either a change in the protein's total abundance or a change in how accessible a particular form of that protein is to the chosen method.
Gerontologist Steve Horvath proposes comparing the age estimated from blood with the function of aged tissue. The analysis then becomes the starting point for determining which processes changed the overall profile, where their source may lie, and what the chosen method actually measured.