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Researchers identified 17 plasma proteins associated with all-cause mortality in older adults and found that several were also associated with biological-age measures. The findings were replicated in a second cohort, but they do not show that the proteins cause aging or can predict an individual’s lifespan.
A study of older adults has identified 17 plasma proteins associated with all-cause mortality, with several also tracking measures of biological aging across multiple organ systems. The findings, published in Geromedicine, were assessed in a second cohort, but they do not establish that the proteins cause aging or can predict an individual’s lifespan.
The researchers analyzed levels of 4,265 proteins in blood samples from 1,025 participants in the LonGenity study. Participants were followed for an average of 8.05 years. Using statistical models of time-to-event data, the team examined whether protein levels were associated with death from any cause, then compared mortality-linked proteins with chronic disease burden and proteome-derived measures of biological age.
Higher levels of ERBB1, also called epidermal growth factor receptor, and ANTXR2, or anthrax toxin receptor 2, were associated with lower mortality risk and younger biological age across multiple organ systems. Higher levels of MIC-1/GDF15, HE4 and IGFBP-2 were associated with higher mortality risk and older biological age across multiple systems.
Some associations were more specific: higher MIC-1/GDF15 was linked with older organismal biological age, while ERBB1 was associated with younger liver biological age. The researchers independently evaluated key associations in 1,124 participants from the Baltimore Longitudinal Study of Aging, reporting that key findings were replicated there. The study involved investigators from Albert Einstein College of Medicine, Stony Brook University, the National Institute on Aging, Stanford University School of Medicine, Kannur University and collaborating institutions.
Protein Signals Across Organ Systems
The results add evidence that blood proteins may help researchers examine why people of the same chronological age can differ in health, chronic disease and resilience. Rather than treating age as a single number, the study compared protein levels with biological-age measures for the body as a whole and for individual organs.
The overlap between mortality associations and biological-age measures gives researchers candidate biomarkers and possible biological pathways to investigate in future work on aging and longevity. The associations may help direct studies into how systemic stress, physiological balance and disease relate to aging. They do not, by themselves, show that changing any of these protein levels would lower mortality or slow aging.
For readers, the distinction matters: these are research findings, not a clinical test. The study does not provide a validated way to estimate an individual’s lifespan, diagnose an age-related condition or guide treatment. Any potential clinical use would require further testing and evidence.
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How Researchers Measured Aging
Chronological age records how much time has passed. Biological age is an attempt to capture how the body, or particular organs, may be aging in ways that are not reflected by years alone. The study used proteome-derived measures—estimates based on patterns in proteins—to compare mortality-linked signals with biological age and disease measures.
The work was published as “Exploring mortality-linked proteins: Understanding their association with biological aging, disease phenotypes, signaling pathways, and their implications for longevity” in Geromedicine. Its two-cohort design matters because the researchers could assess whether key associations seen in LonGenity also appeared in participants from the Baltimore Longitudinal Study of Aging. The report describes independent evaluation and replication of key associations, not proof that the results apply to every population or individual.
“The findings may help researchers better understand the biological pathways that connect systemic stress, physiological homeostasis, chronic disease and aging.”
— The study’s researchers, as described in the report
What the Associations Cannot Show
The study identifies statistical associations; it cannot establish whether the proteins contribute to aging or mortality, result from other processes, or reflect a combination of factors. The supplied report does not provide enough detail to assess how much each protein changed risk, how well the measurements could classify individuals, or whether the associations would be useful for clinical decisions.
It is also unclear whether the results generalize beyond the two cohorts of older adults studied. Replication of key associations in a second cohort supports further investigation, but it does not establish performance across different ages, populations or health settings. The findings do not show that measuring or altering these proteins changes health outcomes.
Further Testing Before Clinical Use
The next steps are further research into the mechanisms behind the associations and testing in additional groups of people. Researchers would also need to establish whether the protein measures add useful information beyond existing health indicators and whether they can reliably predict outcomes for individuals.
The current report does not announce a planned clinical trial, a commercial test or a timeline for clinical use. Until further evidence is available, the proteins should be understood as candidates for research, not established tools for assessing personal biological age or mortality risk.
Key Questions
What did the study find?
Researchers identified 17 plasma proteins associated with all-cause mortality among older adults. Several were also associated with proteome-derived measures of biological age across organ systems.
Which proteins were associated with lower or higher risk?
Higher ERBB1 and ANTXR2 levels were associated with lower mortality risk and younger biological age across multiple systems. Higher MIC-1/GDF15, HE4 and IGFBP-2 levels were associated with higher mortality risk and older biological age. These are associations, not proof that the proteins cause the outcomes.
Can a blood test based on these proteins predict how long someone will live?
No clinical lifespan-prediction test was established by this study. The researchers identified associations in two cohorts, but the report says the findings do not provide a clinical test for an individual’s lifespan or disease outcome.
Were the results checked in a second group?
Yes. The researchers evaluated key associations in 1,124 participants from the Baltimore Longitudinal Study of Aging, in addition to the 1,025 LonGenity participants in the primary analysis. That replication supports further research but does not guarantee the results apply to everyone.
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