This paper published in Nature Aging identifies 13 proteins associated with brain ageing in humans related to stress, regeneration and inflammation. Changes in plasma concentrations of these proteins peak at specific ages: 57, 70 and 78 years, suggesting that these times could be key to possible interventions in the brain ageing process. The researchers determined the Brain Age Gap (BAG), an indicator of brain ageing. Among these proteins, Brevican (BCAN) and growth differentiation factor 15 (GDF15) stand out. BCAN and GDF15 levels were associated with dementia, stroke and motor function in addition to ageing. These findings show that protein concentrations change longitudinally, reflecting transitions in brain health at key ages.

The results of this paper have identified biomarkers in blood, the concentrations of which appear to peak at certain ages during ageing that are related to central nervous system processes. The results have focused on middle-aged and older adults. It is possible that a longitudinal analysis, even before the age of 40, could reveal even earlier markers. While the study covers about 11,000 individuals, the majority of participants were of European descent, which limits the generalisability of the results, so further studies in cohorts of other ethnicities would be very beneficial to learn about possible differences or specific markers. Furthermore, these markers are focused on proteins related to brain functions and its immunity, so this could be a partial representation of ageing-related events.

Previously, plasma markers related to ageing have already been identified. This study provides critical information on key moments along the ageing continuum, showing the need for future studies to address some limitations of the cohort used.

This is good work that can complement previous related studies in blood samples, looking at epigenetic changes in DNA related to ageing.

[In terms of possible limitations] Although conducted in China, the work has been done on samples from European individuals, so samples from other origins are lacking.

The study highlights the potential of omics sciences, in this case proteomics, and the reuse of data generated in different studies, as well as the importance of making data openly available in specialised repositories for the advancement of research in different clinical areas.

The authors verify a recent novelty related to the molecular ageing peaks discovered in other studies and applicable to the cognitive field. At the same time, it verifies that pathological ageing is molecularly identifiable in blood plasma, which provides windows for intervention to improve cognitive quality of life throughout the life cycle, and at the same time objectively measure the effects of potential interventions on specific markers.

This study generates important clinical knowledge and verifies a number of factors, but the feasibility of these specific markers must be measured in different cohorts that clearly take into account the effects of gender, culture and race, important variables that can affect both the impact and range of some markers defined in the study.