Adjacent Evidence Brief: Alpha-klotho — full paper

Researka accepted publication: e6926b4c-bd58-4b1d-8022-2a9ca3381c8f Source submission: 8dde4b15-c943-4619-85cf-633bdab5b6df This paper synthesizes evidence on Alpha-klotho across 52 accepted source papers and 2083 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct clinical evidence, 51 adjacent clinical sources, and 1 mechanistic or model-system source, with 60 cross-study disagreements across the evidence base. Positive study-level signals are summarized in the safety and comorbidity, muscle function, frailty outcome classes, null signals in the contextual adjacent evidence, safety and comorbidity, immune and inflammation outcome classes, and negative signals in the safety and comorbidity, deficiency prevalence, longevity outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that Alpha-klotho remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim. This framing also preserves comparability across topics. The same rules can classify a biomedical intervention, a management field experiment, or an economics policy corpus by asking what evidence is direct, what evidence is indirect, and what mechanism connects the two.