Biology subjects

Bahr, L.

Publications and source records attributed to Bahr, L..

3 recordsLinked to original sources

bioRxiv2026

Caffeine extends lifespan by enhancing lysosomal lipolysis in Caenorhabditis elegans

Caffeine is a globally consumed stimulant that has beneficial effects on biological processes including metabolism and aging, but its causal role in physiology remains incompletely understood. By using the roundworm Caenorhabditis elegans, here we show that caffeine extends lifespan by eliciting transcriptional remodeling that enhances lysosomal lipolysis. We found that transcriptomes of aged, caffeine-fed animals shifted toward youthful states. By comparing with three longevity-promoting regimens, including reduced insulin/insulin-like growth factor 1 (IGF-1) signaling, mild reductions in mitochondrial function, and dietary restriction (DR), we showed that caffeine induced a DR-like transcriptional program. Comparison with eat-2 mutants (a genetic DR model) identified lysosomal lipases lipl-1 and lipl-2 as commonly upregulated genes. The induction of lipl-1 and lipl-2 was required for increased lifespan and reduced neutral lipid accumulation by caffeine intake. Together, these findings indicate that caffeine promotes longevity in a DR-like metabolic reprogramming by enhancing lysosome-driven lipolysis.

genetics↗

bioRxiv2025

LIPL-1 and LIPL-2 are TCER-1-regulated Lysosomal Lipases with Distinct Roles in Immunity and Fertility

Reproduction and immunity are fundamental, energy intensive processes that often compete for resources, leading to trade-offs observed across diverse species. Lipid metabolism plays a crucial role in integrating these processes, particularly during stressful conditions such as pathogenic infections. Yet the molecular mechanisms governing this integration remain poorly understood. TCER-1, the C. elegans homolog of mammalian TCERG1, suppresses immunity and promotes fertility, especially upon maternal infection. Here, we show that TCER-1 regulates two conserved lysosomal lipases, lipl-1 and lipl-2, to balance reproduction, immunity and lifespan. Using transcriptomic, lipidomic, and molecular-genetic analyses, we demonstrate that while both lipl-1 and lipl-2 mediate infection-induced lipid remodeling, lipl-1 enhances immunity and catalyzes the accumulation of ceramide species linked to stress response and longevity, whereas, lipl-2 unexpectedly does not. Both lipases contribute towards fertility outcomes, but lipl-2 is especially critical for maintaining embryonic-eggshell integrity during maternal infection and aging. Strikingly, expression of human lysosomal acid lipase (LAL), the ortholog of lipl genes, rescues the immune defects triggered by lipl-l loss and enhances immune resilience. Together, these findings uncover functionally distinct roles for lipl-1 and lipl-2 in modulating lipid species that shape immune fitness, healthspan and reproductive health, and suggest a potentially conserved mechanism by which lipid metabolism links fertility and immunity.

genetics↗

bioRxiv2025

Antibody response to Aedes aegypti D7L1+2 salivary proteins as marker of aggregate vector exposure and correlate of dengue virus susceptibility

Aedes aegypti mosquitoes transmit several arboviruses of public health importance. Among these is dengue virus (DENV), a flavivirus whose global infection rates continue to rise each year. With limited options available for preventing or treating DENV infections, mosquito control remains the most widely implemented strategy to combat DENV transmission. Due to the global distribution of DENV, which infects an estimated 400 million people per year, vector suppression practices vary drastically by country and/or region and even small differences in microenvironment can significantly impact vector abundance. There remains a significant need to better understand vector exposure rates at an individual level to disentangle vector exposure and arboviral infection rates. To this end, we have optimized a serologic assay to assess the abundance of antibodies directed against the mosquito salivary proteins AeD7L1+2 as a surrogate metric of vector exposure. Utilizing this assay, we found that anti-D7L1+2 IgG levels were unable to identify low levels of Aedes exposure in individuals with limited prior Aedes exposure, indicating they are unreliable markers of an individuals recent exposure to low levels of these vectors. However, antibody levels against D7L1+2 were robust in plasma samples from individuals living in Aedes endemic regions. These antibody levels reflected seasonal changes in Aedes abundance and exposure, indicating their potential for use as an aggregate marker of vector exposure. Additionally, we found that there were slight negative associations with anti-D7L1+2 IgG levels and age in our cohort. Interestingly, we also found that lower titers of anti-AeD7L1+2 IgG correlated with higher infection burden in households. This finding has implications for the potential interaction between AeD7 proteins and DENV during infection events that will require further study.

immunology↗