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1. Higher temperature accelerates the aging-dependent weakening of the melanization immune response in mosquitoes

   https://doi.org/10.1371/journal.ppat.1011935  

   Martin, Lindsay E.; Hillyer, Julián F. (January 2024, PLOS Pathogens)

   McGraw, Elizabeth A. (Ed.)

   The body temperature of mosquitoes, like most insects, is dictated by the environmental temperature. Climate change is increasing the body temperature of insects and thereby altering physiological processes such as immune proficiency. Aging also alters insect physiology, resulting in the weakening of the immune system in a process called senescence. Although both temperature and aging independently affect the immune system, it is unknown whether temperature alters the rate of immune senescence. Here, we evaluated the independent and combined effects of temperature (27°C, 30°C and 32°C) and aging (1, 5, 10 and 15 days old) on the melanization immune response of the adult female mosquito, Anopheles gambiae. Using a spectrophotometric assay that measures phenoloxidase activity (a rate limiting enzyme) in hemolymph, and therefore, the melanization potential of the mosquito, we discovered that the strength of melanization decreases with higher temperature, aging, and infection. Moreover, when the temperature is higher, the aging-dependent decline in melanization begins at a younger age. Using an optical assay that measures melanin deposition on the abdominal wall and in the periostial regions of the heart, we found that melanin is deposited after infection, that this deposition decreases with aging, and that this aging-dependent decline is accelerated by higher temperature. This study demonstrates that higher temperature accelerates immune senescence in mosquitoes, with higher temperature uncoupling physiological age from chronological age. These findings highlight the importance of investigating the consequences of climate change on how disease transmission by mosquitoes is affected by aging. 

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2. Age-related change in adult chimpanzee social network integration

   https://doi.org/10.1093/emph/eoab040  

   Thompson González, Nicole; Machanda, Zarin; Otali, Emily; Muller, Martin N.; Enigk, Drew K.; Wrangham, Richard; Emery Thompson, Melissa (December 2021, Evolution, Medicine, and Public Health)

   Abstract BackgroundSocial isolation is a key risk factor for the onset and progression of age-related disease and mortality in humans. Nevertheless, older people commonly have narrowing social networks, with influences from both cultural factors and the constraints of senescence. We evaluate evolutionarily grounded models by studying social aging in wild chimpanzees, a system where such influences are more easily separated than in humans, and where individuals are long-lived and decline physically with age. MethodologyWe applied social network analysis to examine age-related changes in social integration in a 7+ year mixed-longitudinal dataset on 38 wild adult chimpanzees (22 females, 16 males). Metrics of social integration included social attractivity and overt effort (directed degree and strength), social roles (betweenness and local transitivity) and embeddedness (eigenvector centrality) in grooming networks. ResultsBoth sexes reduced the strength of direct ties with age (males in-strength, females out-strength). However, males increased embeddedness with age, alongside cliquishness. These changes were independent of age-related changes in social and reproductive status. Both sexes maintained highly repeatable inter-individual differences in integration, particularly in mixed-sex networks. Conclusions and implicationsAs in humans, chimpanzees appear to experience senescence-related declines in social engagement. However, male social embeddedness and overall sex differences were patterned more similarly to humans in non-industrialized versus industrialized societies. Such comparisons suggest common evolutionary roots to ape social aging and that social isolation in older humans may hinge on novel cultural factors of many industrialized societies. Lastly, individual and sex differences are potentially important mediators of successful social aging in chimpanzees, as in humans.Lay summary: Few biological models explain why humans so commonly have narrowing social networks with age, despite the risk factor of social isolation that small networks pose. We use wild chimpanzees as a comparative system to evaluate models grounded in an evolutionary perspective, using social network analysis to examine changes in integration with age. Like humans in industrialized populations, chimpanzees had lower direct engagement with social partners as they aged. However, sex differences in integration and older males’ central positions within the community network were more like patterns of sociality in several non-industrialized human populations. Our results suggest common evolutionary roots to human and chimpanzee social aging, and that the risk of social isolation with age in industrialized populations stems from novel cultural factors. 

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3. Male Age and Wolbachia Dynamics: Investigating How Fast and Why Bacterial Densities and Cytoplasmic Incompatibility Strengths Vary

   https://doi.org/10.1128/mBio.02998-21  

   Shropshire, J. Dylan; Hamant, Emily; Cooper, Brandon S. (December 2021, mBio)

   Dubilier, Nicole (Ed.)

   ABSTRACT Endosymbionts can influence host reproduction and fitness to favor their maternal transmission. For example, endosymbiotic Wolbachia bacteria often cause cytoplasmic incompatibility (CI) that kills uninfected embryos fertilized by Wolbachia -modified sperm. Infected females can rescue CI, providing them a relative fitness advantage. Wolbachia -induced CI strength varies widely and tends to decrease as host males age. Since strong CI drives Wolbachia to high equilibrium frequencies, understanding how fast and why CI strength declines with male age is crucial to explaining age-dependent CI’s influence on Wolbachia prevalence. Here, we investigate if Wolbachia densities and/or CI gene ( cif ) expression covary with CI-strength variation and explore covariates of age-dependent Wolbachia -density variation in two classic CI systems. w Ri CI strength decreases slowly with Drosophila simulans male age (6%/day), but w Mel CI strength decreases very rapidly (19%/day), yielding statistically insignificant CI after only 3 days of Drosophila melanogaster adult emergence. Wolbachia densities and cif expression in testes decrease as w Ri-infected males age, but both surprisingly increase as w Mel-infected males age, and CI strength declines. We then tested if phage lysis, Octomom copy number (which impacts w Mel density), or host immune expression covary with age-dependent w Mel densities. Only host immune expression correlated with density. Together, our results identify how fast CI strength declines with male age in two model systems and reveal unique relationships between male age, Wolbachia densities, cif expression, and host immunity. We discuss new hypotheses about the basis of age-dependent CI strength and its contributions to Wolbachia prevalence. IMPORTANCE Wolbachia bacteria are the most common animal-associated endosymbionts due in large part to their manipulation of host reproduction. Many Wolbachia cause cytoplasmic incompatibility (CI) that kills uninfected host eggs. Infected eggs are protected from CI, favoring Wolbachia spread in natural systems and in transinfected mosquito populations where vector-control groups use strong CI to maintain pathogen-blocking Wolbachia at high frequencies for biocontrol of arboviruses. CI strength varies considerably in nature and declines as males age for unknown reasons. Here, we determine that CI strength weakens at different rates with age in two model symbioses. Wolbachia density and CI gene expression covary with w Ri-induced CI strength in Drosophila simulans , but neither explain rapidly declining w Mel-induced CI in aging D. melanogaster males. Patterns of host immune gene expression suggest a candidate mechanism behind age-dependent w Mel densities. These findings inform how age-dependent CI may contribute to Wolbachia prevalence in natural systems and potentially in transinfected systems. 

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4. Ontogeny of Carbon Monoxide-Related Gene Expression in a Deep-Diving Marine Mammal

   https://doi.org/10.3389/fphys.2021.762102  

   Piotrowski, Elizabeth R.; Tift, Michael S.; Crocker, Daniel E.; Pearson, Anna B.; Vázquez-Medina, José P.; Keith, Anna D.; Khudyakov, Jane I. (October 2021, Frontiers in Physiology)

   Marine mammals such as northern elephant seals (NES) routinely experience hypoxemia and ischemia-reperfusion events to many tissues during deep dives with no apparent adverse effects. Adaptations to diving include increased antioxidants and elevated oxygen storage capacity associated with high hemoprotein content in blood and muscle. The natural turnover of heme by heme oxygenase enzymes (encoded by HMOX1 and HMOX2 ) produces endogenous carbon monoxide (CO), which is present at high levels in NES blood and has been shown to have cytoprotective effects in laboratory systems exposed to hypoxia. To understand how pathways associated with endogenous CO production and signaling change across ontogeny in diving mammals, we measured muscle CO and baseline expression of 17 CO-related genes in skeletal muscle and whole blood of three age classes of NES. Muscle CO levels approached those of animals exposed to high exogenous CO, increased with age, and were significantly correlated with gene expression levels. Muscle expression of genes associated with CO production and antioxidant defenses ( HMOX1 , BVR , GPX3 , PRDX1 ) increased with age and was highest in adult females, while that of genes associated with protection from lipid peroxidation ( GPX4 , PRDX6 , PRDX1 , SIRT1 ) was highest in adult males. In contrast, muscle expression of mitochondrial biogenesis regulators ( PGC1A , ESRRA , ESRRG ) was highest in pups, while genes associated with inflammation ( HMOX2 , NRF2 , IL1B ) did not vary with age or sex. Blood expression of genes involved in regulation of inflammation ( IL1B , NRF2 , BVR , IL10 ) was highest in pups, while HMOX1 , HMOX2 and pro-inflammatory markers ( TLR4 , CCL4 , PRDX1 , TNFA ) did not vary with age. We propose that ontogenetic upregulation of baseline HMOX1 expression in skeletal muscle of NES may, in part, underlie increases in CO levels and expression of genes encoding antioxidant enzymes. HMOX2 , in turn, may play a role in regulating inflammation related to ischemia and reperfusion in muscle and circulating immune cells. Our data suggest putative ontogenetic mechanisms that may enable phocid pups to transition to a deep-diving lifestyle, including high baseline expression of genes associated with mitochondrial biogenesis and immune system activation during postnatal development and increased expression of genes associated with protection from lipid peroxidation in adulthood. 

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5. Mathematical Modeling Suggests That Monocyte Activity May Drive Sex Disparities during Influenza Infection

   https://doi.org/10.3390/v16060837  

   Liparulo, Tatum S; Shoemaker, Jason E (May 2024, Viruses)

   In humans, females of reproductive age often experience a more severe disease during influenza A virus infection, which may be due to differences in their innate immune response. Sex-specific outcomes to influenza infection have been recapitulated in mice, enabling researchers to study viral and immune dynamics in vivo in order to identify immune mechanisms that are differently regulated between the sexes. This study is based on the hypothesis that sex-specific outcomes emerge due to differences in the rates/speeds that select immune components respond. Using publicly available sex-specific murine data, we utilized dynamic mathematical models of the innate immune response to identify candidate mechanisms that may lead to increased disease severity in female mice. We implemented a large computational screen using the Bayesian information criterion (BIC), wherein the goodness of fit of the competing model scenarios is balanced against complexity (i.e., the number of parameters). Our results suggest that having sex-specific rates for proinflammatory monocyte induction by interferon and monocyte inhibition of virus replication provides the simplest (lowest BIC) explanation for the difference observed in the male and female immune responses. Markov-chain Monte Carlo (MCMC) analysis and global sensitivity analysis of the top performing scenario were performed to provide rigorous estimates of the sex-specific parameter distributions and to provide insight into which parameters most affect innate immune responses. Simulations using the top-performing model suggest that monocyte activity could be a key target to reduce influenza disease severity in females. Overall, our Bayesian statistical and dynamic modeling approach suggests that monocyte activity and induction parameters are sex-specific and may explain sex-differences in influenza disease immune dynamics. 

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