To probe the underlying mechanisms implicated in brain- and immune system- related longevity,
357 we performed gene ontology enrichment analyses of the top ten brain and immune aging model
358 proteins based on mortality risk FIBA scores (Extended Data Fig. 6f-g; Fig. 4f-g). Selection of
359 brain- or immune system- specific plasma proteins as background for the enrichment test did not
360 result in significant associations, so we used all genes as background. Perineuronal net was the
361 most enriched brain pathway (BCAN, PTPRZ1, NCAN) and secretory granule was the most
362 enriched immune system pathway. Intriguingly, neuroinflammation was another enriched immune
363 system pathway, composed of metalloproteinase-9 (MMP9), a regulator of perineuronal net
364 composition, as well as tumor necrosis factor receptor superfamily member 1B (TNFSRF1B), and
365 integrin alpha M (ITGAM) also known as CD11B. Youthful brain agers had higher levels of BCAN
366 and NCAN and youthful immune agers had lower levels of MMP9
