Biology subjects

Cobham, A. E.

Publications and source records attributed to Cobham, A. E..

3 recordsLinked to original sources

bioRxiv2024

Cave Adaptation Favors Aging Resilience in the Mexican Tetra

All animals age, but the rate at which some species age varies widely. What environmental pressures and what molecular factors underlie the remarkable diversity in aging and lifespan across species remains largely enigmatic. The Mexican tetra, Astyanax mexicanus, serves as an intriguing new model to study how adaptations to different environments can change aging. This species exists as two morphotypes: the river-dwelling surface fish, which inhabits environments rich in food and light, and the blind cave-adapted cavefish, that thrive in dark, nutrient-limited but predator free environments. Nutrient limitation and lack of predation are known to impact lifespan, however, how adaption to such environments changes the aging trajectory in this species remains unknown. Here, we compared aging markers between surface and cavefish populations, focusing on morphological and behavioral changes, as well as molecular signatures, and found that aging markers are pronounced and evident in surface fish, whereas these signatures are less distinct in aged cavefish. Using zebrafish, we explored the contribution of the cavefish insulin receptor mutation to longevity. Although the insulin receptor mutation is sufficient to increase lifespan in fish, our findings suggest its impact is limited. Instead, our data indicate that metabolic shifts, particularly those related to mitochondrial function, may be key contributors to the extended longevity observed in cavefish.

evolutionary biology↗

bioRxiv2024

Starvation resistant cavefish reveal conserved mechanisms of starvation-induced hepatic lipotoxicity

Starvation causes the accumulation of lipid droplets in the liver, a somewhat counterintuitive phenomenon that is nevertheless conserved from flies to humans. Much like fatty liver resulting from overfeeding, hepatic lipid accumulation (steatosis) during undernourishment can lead to lipotoxicity and atrophy of the liver. Here, we found that while surface populations of Astyanax mexicanus undergo this evolutionarily conserved response to starvation, the starvation-resistant cavefish larvae of the same species do not display an accumulation of lipid droplets upon starvation. Moreover, cavefish are resistant to liver atrophy during starvation, providing a unique system to explore strategies for liver protection. Using comparative transcriptomics between zebrafish, surface fish, and cavefish, we identified the fatty acid transporter slc27a2a/fatp2 to be correlated with the development of fatty liver. Pharmacological inhibition of slc27a2a in zebrafish rescues steatosis and atrophy of the liver upon starvation. Further, down-regulation of FATP2 in drosophila larvae inhibits the development of starvation-induced steatosis, suggesting the evolutionary conserved importance of the gene in regulating fatty liver upon nutrition deprivation. Overall, our study identifies a conserved, druggable target to protect the liver from atrophy during starvation. One-Sentence SummaryCavefish evolved protection from starvation-induced liver damage through reduction of fatty acid uptake regulated by FATP2, a mechanism conserved through 400 million years of animal evolution.

cell biology↗

bioRxiv2020

Maintaining robust size across environmental conditions is achieved through plastic growth dynamics in the central nervous system of Drosophila melanogaster

Organ growth is tightly regulated across environmental conditions to generate appropriate final size. While the size of some organs is free to vary, others need to maintain constant size to function properly. This poses a unique problem: how is robust final size achieved when environmental conditions can alter some major growth processes? While we know that brain growth is "spared" from the effects of the environment from humans to fruit flies, we do not understand how this process alters growth dynamics across brain compartments. Here, we explore how this robustness in brain size is achieved by examining differences in growth patterns between the larval body, the brain, and a brain compartment - the mushroom bodies - in Drosophila melanogaster across both thermal and nutritional conditions. We identify key differences in patterns of growth between the whole brain and mushroom bodies that are likely to underlie robustness of final organ shape. Further, we show that these differences produce distinct brain shapes across environments. Significance of StudyA long-standing question in Biology has been how fully functional multicellular organisms with highly specialized organs are generated, given that organs initiate growth at different times across development. Although the genetic mechanisms that underlie growth has been studied extensively, we are yet to understand how growth pattern of organs produces distinct final shapes across changing environmental conditions. We use the Drosophila brain, to reveal that key differences in growth dynamics are likely to underlie robustness of final organ shape and are tuned by nutrition and temperature. Further deepening our knowledge of how final organ shape is maintained across environmental conditions.

developmental biology↗