The Shadow Dogma: A Hypothesis of Fragment-Inheritance Aging Mediated by Immune Distribution

Aging biology has organized its major processes — loss of proteostasis, cellular senescence, inflammaging, and the accumulation of aggregated proteins — largely as parallel phenomena. We propose, and label throughout as a hypothesis, that these may be partial readouts of one under-measured currency: low-abundance, post-translationally modified peptides and conformational fragment burden. We term the proposed channel the Shadow Dogma: a peptide-to-peptide conformational information channel that runs alongside the Central Dogma of molecular biology. The channel's existence is established at its base — prion and prion-like templated conformational conversion, and protein-only inheritance in fungal and yeast model organisms [ATOM: PRION-CHANNEL] — but its reach as an aging-relevant, immune-distributed, transgenerational network is the open hypothesis. We integrate this with immune aging: MHC peptide presentation as a candidate readout of processed-fragment burden (a distributed sensing/selection hypothesis, not asserted to transport or copy conformation between tissues), immunosenescent clearance failure as a candidate accumulation mechanism, and inflammaging as the systemic readout [ATOM: MHC-BROADCAST-CANONICAL]. A non-chromatin germline cascade — microchimerism, fetal oogenesis, and the oocyte as a long-lived proteostatic substrate — is proposed as a possible transgenerational substrate. Because the proposed channel is material rather than a chromatin mark, it would not be erased by the methylation reset that constrains epigenetic transgenerational inheritance — though it would still face the gametogenesis, fertilization, dilution, and degradation barriers that any transgenerational channel must clear. We also report the critical experiment that failed: cross-protein disorder-state transfer is null-consistent under composition-matched shuffle. The decisive unmet test is a longitudinal, proteome-wide measurement of fragment burden jointly with immune processing across the lifespan.