An evolving AI research projectBackground · goals · methodsUpdated 1 Oct 2026

Approaches to aging

Cumulative update · 1 Oct 2026 A new autophagy approach connects protein findings with motor function in a TDP-43 mouse model. Tau-vesicle data belong to a different experimental route. This comparison strengthens the appraisal strategy but does not confirm AG-T01: 🔵 Level 2, low confidence. Daily report 1 Oct 2026 →

What may counter age-related functional decline · Updated 28 September 2026

This list grows with the evidence. Its first entries concern human function; subsequent entries are mechanistic candidates or untested hypotheses. Inclusion does not establish slowing of human aging. The order is not a personal treatment recommendation.

AG-A01 · Structured physical activity

Human function · Project level 1

Outcome / target: Less major mobility disability than with health education.
Population / model: Older adults at mobility risk.
Evidence: Randomised; functional endpoint.
Limits / counterevidence: Serious harms not excluded; no general aging reversal.
Next desk check: Check adherence, safety and separate long-term replications.
Sources: AG-J01 · 2014-05-27

AG-A02 · Combined programs for cognition

Human function · Project level 1

Outcome / target: Small composite-test advantages over each study’s comparator.
Population / model: People at elevated cognitive risk.
Evidence: Two randomised cohorts; related programs.
Limits / counterevidence: Components unresolved; dementia prevention unproven. Assess burdens.
Next desk check: Check contact time, practice effects, daily relevance and counterstudies.
Sources: AG-J02 · 2015-03-12; AG-J03 · 2025-07-28

AG-A03 · TIMP2 as a functional candidate

Preclinical · Project level 1

Outcome / target: Target: plasticity with preserved connections.
Population / model: Mouse.
Evidence: Preclinical; mechanism unresolved.
Limits / counterevidence: Direct neuronal action competes with microglial mediation. Also separate degradation from export; lower cellular loading does not establish safe disposal. The new tau source is a countercontext, not TIMP2 evidence. 30 Sep: the audited assays do not identify the mass balance; no degradation rate calculated.
Next desk check: Assess the already identified primary study DOI 10.1126/scitranslmed.aea4205 for model, delivery, functional endpoint, duration and data dependencies; compare with AG-D03. Verify Guo experimental units, allocation and timing; revisit unresolved AG-D01 supplement questions only with new access.
Sources: AG-R01 · 2026-08-12; AG-R05 · 2017-04-19; AG-R08 · 2023-06-15

AG-A04 · Targeted FTL1 regulation

Preclinical · Project level 1

Outcome / target: Target: reliable neuronal function.
Population / model: Mouse.
Evidence: Mechanistic candidate.
Limits / counterevidence: Avoid blanket iron suppression; transferability unresolved.
Next desk check: Check cellular specificity, exposure and separate functional replication.
Sources: AG-S09 · 2025-08-19

AG-A05 · Redox-dependent protein control

Preclinical · Project level 1

Outcome / target: Target: function after selective DUB modulation.
Population / model: Vertebrate models.
Evidence: Mechanistic candidate.
Limits / counterevidence: Enzyme activity does not establish cognition; broad interventions ambiguous.
Next desk check: Seek selective mediation and functional counterevidence.
Sources: AG-S08 · 2026-04-21

AG-A06 · Mitochondrial quality control

Preclinical · Project level 1

Outcome / target: Target: actual restoration beyond favourable markers.
Population / model: Mouse.
Evidence: Limited; functional findings differ.
Limits / counterevidence: Do not equate prevention with reversal.
Next desk check: Prioritise age- and strain-matched comparisons.
Sources: AG-R03 · 2026-03-05

AG-A07 · Spatial control of regeneration

Preclinical · Project level 1

Outcome / target: Target: correct reconnection following repair.
Population / model: Axolotl; injury.
Evidence: Comparative regeneration biology.
Limits / counterevidence: Tissue regrowth does not establish human aging benefit.
Next desk check: Check conserved mechanisms and transfer limits.
Sources: AG-S03 · 2025-05-21

AG-A08 · Understand senescence over time

Preclinical · Project level 1

Outcome / target: Target: repair without chronic functional harm.
Population / model: Axolotl; regeneration.
Evidence: Context-dependent mechanistic candidate.
Limits / counterevidence: No basis for indiscriminate cell removal.
Next desk check: Compare timing, cell type and state resolution.
Sources: AG-S01 · 2023-10-24

AG-A09 · AG-T01: selective cargo degradation

Hypothesis · Project level 2

Outcome / target: Hypothesis: jointly improve degradation, synapse preservation and function.
Population / model: Proposed aged neuronal system.
Evidence: Untested project synthesis.
Limits / counterevidence: Partial mediation and cargo selectivity unconfirmed. 30 Sep: the audited assays do not identify the mass balance; no degradation rate calculated.
Next desk check: Assess the already identified primary study DOI 10.1126/scitranslmed.aea4205 for model, delivery, functional endpoint, duration and data dependencies; compare with AG-D03. Verify Guo experimental units, allocation and timing; revisit unresolved AG-D01 supplement questions only with new access.
Sources: AG-R01 · 2026-08-12; AG-R02 · 2026-01-21; AG-R08 · 2023-06-15

AG-A10 · AG-H02: FTL1–redox–DUB

Hypothesis · Project level 2

Outcome / target: Hypothesis: a causal mediation chain.
Population / model: No joint test.
Evidence: Low priority; untested.
Limits / counterevidence: Separate findings do not establish the chain.
Next desk check: First check direct prior evidence and counterevidence.
Sources: AG-S08 · 2026-04-21; AG-S09 · 2025-08-19

Updating: New approaches require a verifiable source or explicit hypothesis basis, a functional target endpoint, model limits and the next decisive countercheck. Failed or narrowed approaches remain visible with reasons. Category, evidence and project level are updated separately.

AG-A11 · Coupling antibodies to autophagy

Preclinical · Project level 1

Outcome / target: TDP-43/AAV: rotarod latency, mean difference of published values +36.46 s (7 values/group). Omitting one value per group: +28.25 to +48.88 s; not a confidence interval.
Population / model: TDP-43ΔNLS mice for motor function; separate TauP301S/sEV route for pathology findings.
Evidence: Preclinical, appraisal provisional: table values recalculated, complete methods unverified.
Limits / counterevidence: Small counts, wide dispersion, experimental units/time horizon unresolved. Normal protein function and durability require appraisal; no human aging efficacy.
Next literature check: Assess the already identified primary study DOI 10.1126/scitranslmed.aea4205 for model, delivery, functional endpoint, duration and data dependencies; compare with AG-D03. Verify Guo experimental units, allocation and timing; revisit unresolved AG-D01 supplement questions only with new access.
Source: AG-D03 · 2026-08-26 · Recalculation and limits