The calculated MTC at Beginning of Cycle (BOC) was found to be $-3.5 \text pcm/^\circ\textC$.
No study is perfect, and peer reviewers of ages-ph-04-001 (if published in a journal like Aging Cell or GeroScience) raised valid concerns:
The corresponding author has stated that a follow-up study — likely ages-ph-04-002 — will address these issues using a more diverse, actively tracked cohort. ages-ph-04-001
The research team analyzed data from 4,231 participants across three independent cohorts:
Key inclusion criteria: No acute illness within 30 days, no diagnosed dementia, and availability of at least four time points over 10 years. The calculated MTC at Beginning of Cycle (BOC)
The analytical pipeline was built using a gradient-boosted ensemble model (XGBoost + a shallow neural network). Unlike traditional clocks that train to minimize mean absolute error (MAE) from chronological age, ages-ph-04-001 introduced a novel loss function: weighted time-to-event prediction.
In plain language: the model was rewarded for correctly predicting who would develop frailty, cardiovascular events, or cognitive impairment within 5 years, not for guessing chronological birthdays. The corresponding author has stated that a follow-up
The resulting variable was named PAO – Physiological Age Offset. PAO is calculated as:
PAO = Predicted Biological Age – Chronological Age
A PAO of +5 means your body functions like someone 5 years older. A PAO of –3 means you are aging slower than your peers.
Pharmaceutical companies testing senolytics (e.g., dasatinib + quercetin, fisetin) could use PAO as a surrogate endpoint in Phase 2 trials, potentially shortening trial duration from years to months.