“Inflammaging” (a term we owe to Claudio Franceschi and co-workers) is defined as “a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status” over the course of the aging process. 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.

While the molecular connections between all the moving parts could certainly be bolstered by focused study, I like where this is going: toward a broader integration of formerly disparate aspects of biogerontology. Also note the increased explanatory power of IGF/FOXO, one of the core longevity control pathways — and, for that matter, another gold star for CR, which lately seems like it could use one.

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