Idea: Many diverse damages funnel into a few chronic damage‑response pathways that dominate hazard late in life (for example, innate immune/inflammaging, senescence/SASP, ER/UPR, mitochondrial ISR, mTOR/IGF). If you quiet or reset the chokepoint(s), function and survival improve broadly.
Why a “bottleneck”: Pathways amplify and propagate dysfunction (e.g., SASP → inflammation → more senescence). These feedbacks create leverage points where modest, targeted relief yields large, system‑wide benefits.
Practical signature: Rapid hazard reduction and multi‑tissue functional gains from pathway‑targeted interventions, even without cataloging/repairing all upstream damages. Biomarkers across modalities (inflammation, clocks, resilience metrics) move in the right direction together.
Classics: Diffuse damage and budget tradeoffs drive aging; no single chokepoint dominates.
Bottleneck: A few feedback‑rich pathways dominate late‑life hazard. If targeted relief yields large, low‑cost gains, that strains purely diffuse‑damage/budget framings.
SENS Damage Repair (de Grey)
SENS: Multiple damage classes must be repaired for substantial gains.
Bottleneck: Quieting chokepoint pathways can rival or exceed stacked repairs. If stacked repairs are still required for big wins after effective bottleneck relief, that weakens Bottleneck primacy.
Epigenetic Information (Sinclair)
Sinclair: Epigenetic mis‑specification is primary; global resets (e.g., OSK) rejuvenate broadly.
Bottleneck: Downstream damage‑response loops are the critical levers. If targeted pathway relief matches or beats OSK on hazard/function with lower risk, that favors Bottleneck; if OSK outperforms regardless of pathway state, that favors Sinclair.
Resilience / Criticality (Fedichev)
Resilience: System dynamics can be tuned without pathway specificity.
Bottleneck: Specific molecular circuits explain much of the hazard. If hazard drops without correcting bottleneck biomarkers, that argues for dynamics‑first over pathway bottlenecks.
Bioelectric / Morphogenetic Control (Levin)
Levin: Loss of pattern “goal” and information flow sits upstream; targeted pattern cues rejuvenate.
Bottleneck: Molecular damage‑response circuits are the primary chokepoints; pattern cues may help but are not required. If pattern‑aware cues outperform pathway relief across tissues, that weakens Bottleneck.
Pathogen Control (Lidsky)
PC: Chronic activation is often maintained by infections; anti‑pathogen measures should calm pathways and reduce hazard.
Bottleneck: Chronic activation can be intrinsic/self‑sustaining; targeted pathway relief should reduce hazard even when pathogen burden is unchanged. If anti‑pathogen plans fail to normalize bottleneck markers while targeted relief works, that favors Bottleneck; the reverse favors PC.
PC further claims lifespan varies with population structure (dispersal, eusociality, cohorting), which single‑pathway bottlenecks don’t explain on their own.