From adolescence to late aging: A comprehensive review of social behavior, alcohol, and neuroinflammation across the lifespan.

The passage of time dictates the pace at which humans and other organisms age but falls short of providing a complete portrait of how environmental, lifestyle and underlying biological processes contribute to senescence. Two fundamental features of the human experience that change dramatically across the lifespan include social interactions and, for many, patterns of alcohol consumption. Rodent models show great utility for understanding complex interactions among aging, social behavior and alcohol use and abuse, yet little is known about the neural changes in late aging that contribute to the natural decline in social behavior. Here, we posit that aging-related neuroinflammation contributes to the insipid loss of social motivation across the lifespan, an effect that is exacerbated by patterns of repeated alcohol consumption observed in many individuals. We provide a comprehensive review of (i) neural substrates crucial for the expression of social behavior under non-pathological conditions; (ii) unique developmental/lifespan vulnerabilities that may contribute to the divergent effects of low-and high-dose alcohol exposure; and (iii) aging-associated changes in neuroinflammation that may sit at the intersection between social processes and alcohol exposure. In doing so, we provide an overview of correspondence between lifespan/developmental periods between common rodent models and humans, give careful consideration to model systems used to aptly probe social behavior, identify points of coherence between human and animal models, and point toward a multitude of unresolved issues that should be addressed in future studies. Together, the combination of low-dose and high-dose alcohol effects serve to disrupt the normal development and maintenance of social relationships, which are critical for both healthy aging and quality of life across the lifespan. Thus, a more complete understanding of neural systems-including neuroinflammatory processes-which contribute to alcohol-induced changes in social behavior will provide novel opportunities and targets for promoting healthy aging.