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Plasma proteins offer clues to biological aging and mortality risk (opens in a new tab)

news-medical.net · 2026-10-27

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Plasma proteins offer clues to biological aging and mortality risk

news-medical.net · 2026-10-27

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Exploring mortality-linked proteins: Understanding their association with biological aging, disease phenotypes, signaling pathways, and their implications for longevity

Geromedicine · 2026

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Claim 1 of 4SupportedA new study published in Geromedicine identified 17 plasma proteins associated with all-cause mortality in older adults and found that several also track with measures of biological aging across multiple organ systems.View evidenceHide evidence

As stated17 plasma proteins

Why this verdict

The abstract-level profile reports a LonGenity prospective cohort analysis identifying 17 plasma proteins significantly associated with all-cause mortality, and downstream analyses linking several mortality-associated proteins to organismal or organ-specific biological age. The story frames this as association/tracking rather than causation.

Study evidence

Seventeen plasma proteins were significantly associated with all-cause mortality in the LonGenity discovery cohort (n = 1,025; 4,265 proteins measured; mean follow-up 8.05 years).

“We conducted a prospective cohort study of 1,025 older adults from the LonGenity study, analyzing 4,265 plasma proteins.”

Study evidence

Higher plasma ERBB1 (epidermal growth factor receptor) and ANTXR2 levels were associated with lower mortality risk and younger biological age across multiple organ systems in LonGenity.

“Mortality-associated proteins were further examined for their relationships with chronic disease burden and proteome-derived measures of organismal and organ-specific biological aging.”

Claim 2 of 4SupportedThe research analyzed 4,265 proteins in blood samples from 1,025 older adults in the LonGenity study, with an average follow-up of 8.05 years, and independently evaluated the findings in 1,124 participants from the Baltimore Longitudinal Study of Aging.View evidenceHide evidence

As stated4,265 proteins; 1,025 primary participants; 1,124 validation participants; 8.05 years follow-up

Why this verdict

The profile states that 4,265 plasma proteins were analyzed in 1,025 LonGenity participants, mortality associations were assessed over a mean 8.05 years of follow-up, and findings were independently validated in 1,124 BLSA participants.

Study evidence

Seventeen plasma proteins were significantly associated with all-cause mortality in the LonGenity discovery cohort (n = 1,025; 4,265 proteins measured; mean follow-up 8.05 years).

“We conducted a prospective cohort study of 1,025 older adults from the LonGenity study, analyzing 4,265 plasma proteins.”

Study evidence

The authors report independent replication of the LonGenity-discovered associations between mortality-associated plasma proteins and measures of organismal and organ-specific biological aging in the Baltimore Longitudinal Study of Aging (n = 1,124).

“Findings were independently validated in 1,124 participants from the Baltimore Longitudinal Study of Aging (BLSA).”

Claim 3 of 4SupportedHigher levels of ERBB1 and ANTXR2 were associated with lower mortality risk and younger biological age across multiple organ systems, while higher levels of MIC-1/GDF15, HE4, and IGFBP-2 were associated with higher mortality risk and older biological age across multiple organ systems.View evidenceHide evidence

As statedfive named proteins highlighted

Why this verdict

The abstract-level profile specifically reports that higher ERBB1 and ANTXR2 were associated with lower mortality risk and younger biological age across multiple organ systems, while higher MIC-1/GDF15, HE4, and IGFBP-2 were associated with increased mortality and older biological age across multiple organ systems.

Study evidence

Seventeen plasma proteins were significantly associated with all-cause mortality in the LonGenity discovery cohort (n = 1,025; 4,265 proteins measured; mean follow-up 8.05 years).

“We conducted a prospective cohort study of 1,025 older adults from the LonGenity study, analyzing 4,265 plasma proteins.”

Study evidence

Higher plasma ERBB1 (epidermal growth factor receptor) and ANTXR2 levels were associated with lower mortality risk and younger biological age across multiple organ systems in LonGenity.

“Mortality-associated proteins were further examined for their relationships with chronic disease burden and proteome-derived measures of organismal and organ-specific biological aging.”

Claim 4 of 4SupportedThe article says the study does not establish that these proteins cause aging or mortality and does not provide a clinical blood test for predicting an individual's lifespan or disease outcome.View evidenceHide evidence

Why this verdict

The paper profile describes observational cohort and cross-sectional association analyses, with limitations noting that causality cannot be inferred. It also describes biomarker associations rather than a validated individual clinical prediction test; the abstract-level profile provides no clinical test performance, individual lifespan prediction model, or disease-outcome prediction validation.

Study evidence

Seventeen plasma proteins were significantly associated with all-cause mortality in the LonGenity discovery cohort (n = 1,025; 4,265 proteins measured; mean follow-up 8.05 years).

“We conducted a prospective cohort study of 1,025 older adults from the LonGenity study, analyzing 4,265 plasma proteins.”

Study evidence

Higher plasma ERBB1 (epidermal growth factor receptor) and ANTXR2 levels were associated with lower mortality risk and younger biological age across multiple organ systems in LonGenity.

“Mortality-associated proteins were further examined for their relationships with chronic disease burden and proteome-derived measures of organismal and organ-specific biological aging.”

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7 things the story did carry across

Primary LonGenity discovery analysis: 1,025 older adults, 4,265 plasma proteins, Cox proportional hazards modeling over mean 8.05 years, identifying 17 proteins associated with all-cause mortality.
Named mortality-protein directions: ERBB1 and ANTXR2 lower mortality risk; MIC-1/GDF15, HE4, and IGFBP-2 higher mortality risk.
Downstream associations with proteome-derived organismal and organ-specific biological age, including younger or older biological-age patterns across multiple organ systems.
External validation/replication in the Baltimore Longitudinal Study of Aging with 1,124 participants.
Observational design limitation: protein associations do not establish that the proteins cause aging or mortality.
The study does not establish a clinical blood test or validated individual prediction tool for lifespan or disease outcome.
Generalizability limitation: the discovery cohort consists of older adults, and broader population applicability is not established at abstract depth.

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study summary

Lead result

human in vivo

1Lead resulthuman in vivoIdentify plasma proteins whose baseline levels are associated with subsequent all-cause mortality in older adults.Prospective cohort discovery screen (LonGenity); high-throughput plasma proteomics with time-to-event modelingExpand

In plain English

In a prospective discovery analysis of 1,025 older adults from the LonGenity cohort, baseline levels of 4,265 plasma proteins were measured and associations with subsequent all-cause mortality were tested using Cox proportional hazards regression over a mean follow-up of 8.05 years. Seventeen plasma proteins were reported as significantly associated with all-cause mortality. Examples: higher ERBB1 and ANTXR2 levels were associated with lower mortality risk, while higher MIC-1 (GDF15), HE4, and IGFBP-2 levels were associated with higher mortality risk. The abstract also reports links between several mortality-associated proteins and organismal or organ-specific biological age.

Key findings

Seventeen plasma proteins were significantly associated with all-cause mortality in the LonGenity discovery cohort (n = 1,025; 4,265 proteins measured; mean follow-up 8.05 years).
Higher baseline levels of ERBB1 (epidermal growth factor receptor) and ANTXR2 (anthrax toxin receptor 2) were associated with lower all-cause mortality risk.

“We conducted a prospective cohort study of 1,025 older adults from the LonGenity study, analyzing 4,265 plasma proteins.”

What this piece can’t prove

Observational/prospective cohort design: associations do not establish causation.
High-dimensional discovery screening (4,265 proteins) implies multiple-testing concerns; the abstract does not state the correction method or statistical thresholds used.

3 further details could not be confirmed from the summary.

2human in vivoCharacterize how mortality-associated proteins relate to chronic disease burden and proteome-derived measures of organismal and organ-specific biological aging (pathway/phenotype interpretation within cohort data).observational association analyses (cross-sectional within cohort)Expand

In plain English

In the LonGenity cohort (n=1,025 older adults), the subset of plasma proteins previously identified as associated with all-cause mortality were further analyzed for cross-sectional associations with chronic disease burden and proteome-derived measures of biological aging at the organismal and organ-specific levels. The abstract reports that higher ERBB1 and ANTXR2 levels were linked to lower mortality risk and younger biological age across multiple organ systems, whereas higher MIC-1 (GDF15), HE4, and IGFBP-2 levels were linked to increased mortality and older biological age across multiple organ systems; MIC-1 was specifically associated with older organismal biological age and ERBB1 with younger liver biological age. The abstract notes these associations were independently replicated in the BLSA cohort (n=1,124).

Key findings

Higher plasma ERBB1 (epidermal growth factor receptor) and ANTXR2 levels were associated with lower mortality risk and younger biological age across multiple organ systems in LonGenity.
Higher plasma MIC-1 (GDF15), HE4, and IGFBP-2 levels were associated with increased mortality and older biological age across multiple organ systems in LonGenity.

“Mortality-associated proteins were further examined for their relationships with chronic disease burden and proteome-derived measures of organismal and organ-specific biological aging.”

What this piece can’t prove

Abstract does not provide quantitative effect sizes, confidence intervals, or full model specifications for the protein–aging and protein–disease-burden associations.

4 further details could not be confirmed from the summary.

3human in vivoIndependently validate/replicate the mortality–protein (and related aging/phenotype) associations in an external cohort (BLSA).external cohort replication (BLSA)Expand

In plain English

The paper reports that the mortality-associated plasma protein findings and their relationships with organismal and organ-specific biological aging identified in the LonGenity discovery cohort were independently validated/replicated in an external cohort, the Baltimore Longitudinal Study of Aging (BLSA; n = 1,124). The abstract does not provide cohort-specific analytic details, effect sizes, or which of the 17 proteins were individually replicated.

Key findings

The authors report independent replication of the LonGenity-discovered associations between mortality-associated plasma proteins and measures of organismal and organ-specific biological aging in the Baltimore Longitudinal Study of Aging (n = 1,124).