Abstract
Here, we provide a brief review of the mechanistic connections between immunity and aging—a fundamental biological relationship that remains poorly understood—by considering two intertwined questions: how does aging affect immunity, and how does immunity affect aging? On the one hand, aging contributes to the deterioration of immune function and predisposes the organism to infections (“immuno-senescence”). On the other hand, excessive activation of the immune system can accelerate degenerative processes, cause inflammation and immunopathology, and thus promote aging (“inflammaging”). Interestingly, several recent lines of evidence support the hypothesis that restrained or curbed immune activity at old age (that is, optimized age-dependent immune homeostasis) might actually improve realized immune function and thereby promote longevity. We focus mainly on insights from Drosophila, a powerful genetic model system in which both immunity and aging have been extensively studied, and conclude by outlining several unresolved questions in the field.
Highlights
The ability to respond to the ubiquitous challenge by pathogens is essential throughout organismal life
The Drosophila immune system is strongly affected by the degenerative processes that accompany aging
The widely observed state of chronic inflammation, a loss of cellular immunity, and the gradual deterioration of protective epithelial barriers all contribute to the functional senescence and increased pathogen susceptibility of aging flies[7,114]
Summary
The ability to respond to the ubiquitous challenge by pathogens is essential throughout organismal life. Broderick et al showed that the presence of microbiota strongly affects gut morphology and gene expression, inducing a local immune response (mainly through Imd signaling), upregulating the expression of genes for cell differentiation (JAK/ STAT pathway), and altering metabolism[19] Consistent with these findings, Guo et al observed that the gut epithelia of axenic flies exhibit reduced numbers of mitotically active cells, lower levels of tissue dysplasia, and decreased expression of immune genes[22]. Mutants of mitochondrial peroxiredoxins (dPrx[3] and dPrx5), involved in the regulation of ROS levels, exhibit increased activation of the immune response, whereas overexpression of these peroxiredoxins extends lifespan and delays the age-related inflammatory response[52] It is still not entirely clear whether the strong age-dependent upregulation of immune transcription represents an adaptive and necessary physiological response in order to deal with the increase in pathogen load or whether it reflects the age-progressive loss of the ability to fight off microbial infections. Both the contribution to systemic NF-κB activation and the metabolic impact of Toll signaling would merit close investigation with regard to aging and lifespan in the fly
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