Co-expression analysis identifies neuro-inflammation as a driver of sensory neuron aging in Aplysia californica

Abstract

Aging of the nervous system is typified by depressed metabolism, compromised proteostasis, and increased inflammation that results in cognitive impairment. Differential expression analysis is a popular technique for exploring the molecular underpinnings of neural aging, but technical drawbacks of the methodology often obscure larger expression patterns. Co-expression analysis offers a robust alternative that allows for identification of networks of genes and their putative central regulators. In an effort to expand upon previous work exploring neural aging in the marine model Aplysia californica, we used weighted gene correlation network analysis to identify co-expression networks in a targeted set of aging sensory neurons in these animals. We identified twelve modules, six of which were strongly positively or negatively associated with aging. Kyoto Encyclopedia of Genes analysis and investigation of central module transcripts identified signatures of metabolic impairment, increased reactive oxygen species, compromised proteostasis, disrupted signaling, and increased inflammation. Although modules with immune character were identified, there was no correlation between genes in Aplysia that increased in expression with aging and the orthologous genes in oyster displaying long-term increases in expression after a virus-like challenge. This suggests anti-viral response is not a driver of Aplysia sensory neuron aging.