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The neutrophil to lymphocyte ratio (NLR) is a trans-prognostic biomarker of physiologic stress and inflammation linked to muscle weakness in older adults. Generation of grip force coincides with sustained activity in the primary sensorimotor cortex (SM1). The current study investigates whether whole-brain functional connectivity, i.e., degree centrality (CD) of SM1 relates to grip strength and whether both functional measures are predicted by advancing age as a function of the NLR. A structural regression model investigated main and interactive effects of age and NLR on grip strength and CD of SM1 in 589 adults aged 21-85 years (M = 45.87, SD = 18.06). The model including the entire sample had good fit (χ2(4) = 1.63, p = .804). In individuals aged 50 years and older, age predicted lower grip strength and SM1 CD as a function of increasing NLR. In a model stratified by sex, the effect of age, NLR, and their interaction on grip strength are significant for older men but not older women. Analyses support CD of SM1 at rest as a neural biomarker of grip strength. Grip and its neural underpinnings decrease with advancing age and increasing NLR in mid- to late-life. Age-related decrements in grip strength and functional connectivity of brain regions involved in the generation of dynamic grip appear to be accelerated as a function of systemic physiological stress and inflammation, particularly in older men.

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