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Which biological mechanisms can demonstrably slow or partly reverse age-related functional decline in humans?
Cumulative update · 22 Oct 2026
The methods audit separates donor comparisons from spatial spot analyses. Technical correction does not automatically establish independent evidence. Context hypothesis AG-T01 remains 🔵 Level 2; literature AG-D10 ⚪ Level 1, without intervention evidence. Daily report 22 Oct 2026 →
The leading question · AG-T01 · 🔵 Level 2
Clear harmful proteins. Preserve working synapses?
We connect published studies of TIMP2, microglia and protein turnover. We seek a mechanism that clears harmful cargo while preserving neuronal function. This connection remains an unconfirmed working hypothesis.
Neuronal labeling tracks slowly degraded proteins into microglia. For our model, the key issue is that increased stored cargo can have different causes.
Uptake, degradation and export require separate measurement; this is our methodological inference. Guldner et al. · 21 Jan 2026
C57BL/6 and SAMP8 mice
Better markers do not establish memory recovery
Urolithin A improved molecular measurements in aged C57BL/6 mice without demonstrating recovery in the memory tests examined.
Early/late comparisons also differ by mouse strain. They establish neither a universal timing window nor proven absence of an effect. Jara et al. · 5 Mar 2026
Twelve entries distinguish human functional outcomes, preclinical candidates and hypotheses. LIFE, FINGER and US POINTER provide human benchmarks, without establishing a solution to biological aging.
Each new study should strengthen, constrain or change a specific claim. Independent evidence routes, counterevidence and missing links remain visible. This project conducts no experiments.
16 foundation assignments and 5 deep dives: challenge causal models, critically read published data and connect conflicting studies. Substantive new findings become dated addition packages with their own Wish-List entries.
Science Communication Lab · 2018-02 (recorded) · Elly Tanaka examines the experimental questions behind axolotl regeneration. Recorded in 2018; English, 27:57. Use it as methodological background and compare it with the world's current studies. YouTube
Stanford · 2016-11-10 · Tony Wyss-Coray discusses systemic influences on the aging brain. Stanford lecture, published November 10, 2016; English. Historical research background; results in old mice do not establish efficacy in humans. YouTube
32 selected primary studies, including one labeled preprint. Targeted, non-exhaustive research. Findings, inferences and open hypotheses remain distinct. Study register →
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