DeSousa, C. | Search bioRxiv

bioRxiv2025

SRS microscopy identifies inhibition of vitellogenesis as a mediator of lifespan extension by caloric restriction in C. elegans

The molecular mechanisms of aging are not fully understood. Here, we used label-free Stimulated Raman scattering (SRS) microscopy to investigate changes in proteins and lipids throughout the lifespan of C. elegans. We observed a dramatic buildup of proteins within the body cavity or pseudocoelom of aged adults that was blunted by interventions that extend lifespan: caloric restriction (CR) and the reduced insulin/insulin-like growth factor signaling (IIS) pathway. Using a combination of microscopy, proteomic analysis, and validation with mutant strains, we identified vitellogenins as the key molecular components of the protein buildup in the pseudocoelom. Vitellogenins shuttle nutrients from intestine to embryos and are homologous to human apolipoprotein B, the causal driver of cardiovascular disease. We then showed that CR and knockdown of vitellogenins both extend lifespan by >60%, but their combination has no additional effect on lifespan, suggesting that CR extends the lifespan of C. elegans in part by inhibiting vitellogenesis. The extensive dataset of more than 12,000 images stitched into over 350 whole-animal SRS images of C. elegans at different ages and subjected to different longevity intervention will be a valuable resource for researchers interested in aging.

cell biology↗

bioRxiv2023

Microbiome remodeling through bacterial competition and host behavior enables rapid adaptation to environmental toxins.

Human activity is altering the environment in a rapid pace, challenging the adaptive capacities of genetic variation within animal populations. Animals also harbor extensive gut microbiomes, which play diverse roles in host health and fitness and may help expanding host capabilities. The unprecedented scale of human usage of xenobiotics and contamination with environmental toxins describes one challenge against which bacteria with their immense biochemical diversity would be useful, by increasing detoxification capacities. To explore the potential of bacteria-assisted rapid adaptation, we used Caenorhabditis elegans worms harboring a defined microbiome, and neomycin as a model toxin, harmful for the worm host and neutralized to different extents by some microbiome members. Worms raised in the presence of neomycin showed delayed development and decreased survival but were protected when colonized by neomycin-resistant members of the microbiome. Two distinct mechanisms facilitated this protection: gut enrichment driven by altered bacterial competition for the strain best capable of modifying neomycin; and host avoidance behavior, which depended on the conserved JNK homolog KGB-1, enabling preference and acquisition of neomycin-protective bacteria. We further tested the consequences of adaptation, considering that enrichment for protective strains may represent dysbiosis. We found that neomycin-adapted gut microbiomes caused increased susceptibility to infection as well as an increase in gut lipid storage, suggesting metabolic remodeling. Our proof-of-concept experiments support the feasibility of bacteria-assisted host adaptation and suggest that it may be prevalent. The results also highlight trade-offs between toxin adaptation and other traits of fitness.

evolutionary biology↗