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Stanford Study Develops Blood Test to Estimate Biological Age of Organs and Cell Types

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Blood Test Estimates Biological Age of Organs and Cells, Predicting Disease Risk

A research team at Stanford Medicine has developed a blood-based method to estimate the biological age of multiple organ systems and individual cell types. The method uses analysis of proteins in the blood to generate aging profiles that may predict the risk of developing certain diseases.

Findings from the research have been published in Nature Medicine.

Study Methodology and Scope

The research builds on a prior study involving blood samples from 44,498 participants aged 40–70 from the UK Biobank, with health outcomes tracked for up to 17 years. That study analyzed nearly 3,000 proteins in the blood to determine the biological age of 11 organ systems: brain, muscle, heart, lung, arteries, liver, kidneys, pancreas, immune system, intestine, and fat.

A second study expanded this approach, using data from over 60,000 individuals across three independent cohorts (GNPC, NSHD, UKB). This analysis used two proteomic platforms (SomaScan and Olink) to estimate the biological age of more than 40 specific cell types, including neuronal, immune, glial, endocrine, epithelial, and musculoskeletal cell types.

Key Findings on Organ and Cell Aging

  • The algorithm assigns a biological age to each organ based on protein signatures. An organ classified as "extremely aged" or "extremely youthful" is defined by a deviation of 1.5 standard deviations or more from the norm.
  • One-third of participants in the initial study had at least one organ classified as extremely aged or youthful; one in four had multiple such organs.
  • In the follow-up study, individuals with more than 20 extremely aged cell types had an approximately 34% survival rate over 15 years, compared to approximately 90% survival for those with normal cellular aging.
  • Younger nerve and immune cells were associated with improved survival outcomes.

Disease Risk Associations

Alzheimer's Disease and the Brain

  • An extremely aged brain was associated with a 3.1 times higher risk of developing Alzheimer's disease compared to a normally aged brain. An extremely youthful brain was associated with a reduced risk to one-fourth.
  • Individuals carrying two copies of the APOE4 genetic variant tended to have older astrocytes. Extreme astrocyte aging in APOE4 homozygotes was associated with a threefold higher risk of developing Alzheimer's disease. APOE4 carriers with "young" astrocytes showed a neutralized Alzheimer's risk.
  • Alzheimer's disease was linked to accelerated aging in multiple cell types, including oligodendrocyte precursor cells, inhibitory neurons, intestinal lining cells, and pancreatic cells.

Other Diseases

  • An extremely aged heart predicted atrial fibrillation or heart failure.
  • An extremely aged lung predicted chronic obstructive pulmonary disease (COPD). Among current smokers, extreme aging in alveolar type 2 cells was associated with a 58% increased risk of lung cancer compared to smoking alone.
  • An extremely aged kidney predicted chronic kidney disease.
  • Extreme aging of skeletal muscle cells was associated with a 12.7-fold higher risk of developing amyotrophic lateral sclerosis (ALS), detectable more than three years before clinical diagnosis.

Mortality Risk

  • Brain age was reported as the strongest predictor of overall mortality in the initial study. Extremely aged brains were associated with a 182% increase in death risk over 15 years; extremely youthful brains were associated with a 40% reduction in risk.
  • A polycellular aging risk score (PARS) was developed to classify mortality risk based on cellular aging profiles.

Study Limitations

  • The models relied on annotations from the Human Protein Atlas. Plasma proteins may not fully reflect cellular gene activity.
  • The cohorts were predominantly older and Caucasian. The study authors noted that validation in broader populations is required.

Funding and Commercialization

The study was funded by the National Institutes of Health, the Milky Way Foundation, the Knight Initiative for Brain Resilience, and the Stanford Alzheimer's Disease Research Center.

Senior author Tony Wyss-Coray is a co-founder of Teal Omics and Vero Bioscience, which have licensed the technology for drug target screening and consumer products. The test may become commercially available within 2–3 years, with an initial focus on the brain, heart, and immune system.