Ouroboros notes some joining of dots on the mechanisms of inflammaging: "High levels of inflammatory cytokines in aging tissues have been implicated in immunological dysfunctions and frailty in the very old. What causes this age-related upregulation of inflammation? From Kim et al., we learn of a connection between two 'usual suspects' that might help explain the phenomenon. They propose that NF-kappaB (the no-brainer go-to candidate transcription factor for inflammatory responses) is activated by phosphorylation of FOXO (a key transcription factor in an evolutionarily ancient longevity assurance pathway), which increases with age. Furthermore, calorie restriction (CR) may protect the animal by decreasing overall levels of insulin (and insulin-like growth factor) signaling: less insulin/IGF means less FOXO phosphorylation, leading to reduced oxidative stress. This in turn reduces nuclear translocation of NF-kappaB and a relative diminution of inflammatory cytokine production." The body is a collection of complex, interacting systems with many points of linkage - this is just as true when the systems begin to fail as when they are running according to plan.