RESEARKA

Several clinically important endpoints are represented by only a single study within the corpus, precluding internal replication or assessment of consistency. For example, the association between the retinal age gap and Parkinson's disease risk rests on one report (Hu 2022), as does the link to branch retinal vein occlusion (Nonaka 2026), reproductive aging markers (Miao 2025), and postoperative delirium after hip fracture (Noah 2024). When an outcome class — such as skeletal or musculoskeletal endpoints — is touched by a single source, the synthesis cannot determine whether the finding is robust, population-specific, or an artifact of unmeasured confounding. This single-trial dependency applies to the majority of non-cardiometabolic outcome classes in the corpus, limiting the confidence with which any cross-domain generalization can be made.

Citation Support

• source_1 Nonaka 2026
• source_2 Zhu 2023
• source_3 Chen 2023
• source_4 Chen 2025
• source_5 Miao 2025