HIV, pathology and epigenetic age acceleration in different human tissues
Why this work is in the frame
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Bibliographic record
Abstract
Epigenetic clocks based on patterns of DNA methylation have great importance in understanding aging and disease; however, there are basic questions to be resolved in their application. It remains unknown whether epigenetic age acceleration (EAA) within an individual shows strong correlation between different primary tissue sites, the extent to which tissue pathology and clinical illness correlate with EAA in the target organ, and if EAA variability across tissues differs according to sex. Considering the outsized role of age-related illness in Human Immunodeficiency Virus-1 (HIV), these questions were pursued in a sample enriched for tissue from HIV-infected individuals. We used a custom methylation array to generate DNA methylation data from 661 samples representing 11 human tissues (adipose, blood, bone marrow, heart, kidney, liver, lung, lymph node, muscle, spleen and pituitary gland) from 133 clinically characterized, deceased individuals, including 75 infected with HIV. We developed a multimorbidity index based on the clinical disease history. Epigenetic age was moderately correlated across tissues. Blood had the greatest number and degree of correlation, most notably with spleen and bone marrow. However, blood did not correlate with epigenetic age of liver. EAA in liver was weakly correlated with EAA in kidney, adipose, lung and bone marrow. Clinically, hypertension was associated with EAA in several tissues, consistent with the multiorgan impacts of this illness. HIV infection was associated with positive age acceleration in kidney and spleen. Male sex was associated with increased epigenetic acceleration in several tissues. Preliminary evidence indicates that amyotrophic lateral sclerosis is associated with positive EAA in muscle tissue. Finally, greater multimorbidity was associated with greater EAA across all tissues. Blood alone will often fail to detect EAA in other tissues. While hypertension is associated with increased EAA in several tissues, many pathologies are associated with organ-specific age acceleration.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it