The research community continues to create aging clocks based on omics data at a fair pace. At this point, there are scores of clocks one might chose from if conducting studies on potential therapies to slow or reverse aspects of aging. Yet the primary challenge remains knowing whether any given clock will accurately reflect future outcomes following a specific form of treatment, meaning reduced risk of age-related disease and lowered mortality. Because there is no detailed map linking the omics data making up a clock to underlying mechanisms of aging or outcomes in aging, researchers do not know in advance how an aging clock will react to changes in the mechanisms targeted by a potential treatment for aging, and whether those reactions are useful. The clock might overestimate the impact, it might underestimate the impact. The only way to find out in certainty is to calibrate the clock against the therapy in long-running, expensive studies, and that somewhat defeats the point of having an aging clock.
The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We addressed this by developing a proteomics-based signature of healthspan, termed the Healthspan Proteomic Score (HPS), using proteomic data from the Olink Explore 3072 assay in the UK Biobank Pharma Proteomics Project (53,018 individuals and 2,920 proteins).
A lower HPS was associated with higher mortality risk and several age-related conditions, such as chronic obstructive pulmonary disease, diabetes, heart failure, cancer, myocardial infarction, dementia, and stroke. HPS showed superior predictive accuracy for these outcomes compared to other biological age measures. Proteins associated with HPS were enriched in hallmark pathways such as immune response, inflammation, cellular signaling, and metabolic regulation.
The external validity was evaluated using the Essential Hypertension Epigenetics study with proteomic data also from the Olink Explore 3072 and complementary epigenetic data, making it a valuable tool for assessing healthspan and as a potential surrogate marker to complement existing proteomic and epigenetic biological age measures in geroscience-guided studies.
Link: https://doi.org/10.1073/pnas.2414086122
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