IL-1/MyD88 outranks TNF/IL-6 as an upstream screening candidate, but not as a universal bottleneck

IL-1 / MyD88 should be ranked above TNF/IL-6 as an upstream inflammatory screening candidate, but still below universal longevity bottlenecks

''结论'': When screening immune/inflammation axes for a longevity bottleneck, IL-1/MyD88 deserves higher priority than TNF or IL-6 because it sits more upstream in the hematopoietic inflammaging chain (microbiome-driven HSC decline, emergency myelopoiesis, Tet2+/− clonal hematopoiesis). However, the public evidence still lacks organism-level lifespan or multi-organ healthspan improvement, so it should be treated as a strong upstream amplifier rather than a validated universal bottleneck.

''Evidence pattern'':
# PMID 34525198: IL-1 mediates microbiome-induced inflammaging of hematopoietic stem cells in mice.
# PMID 36379023: Aging drives Tet2+/- clonal hematopoiesis via IL-1 signaling.
# PMID 30988118: Trauma induces emergency hematopoiesis through IL-1/MyD88-dependent production of G-CSF.
# PMID 25114230: IL-1 deficiency prolongs ovarian lifespan in mice, but this is tissue-specific rather than whole-organism evidence.

''Decision rule'': If a cytokine axis mainly explains marrow/HSC and myeloid skew phenotypes, but not broad lifespan/healthspan gains, rank it above local mediators like TNF/IL-6 yet still below candidate master bottlenecks with organism-level readouts.