Biology subjects

Parkhitko, A. A.

Publications and source records attributed to Parkhitko, A. A..

3 recordsLinked to original sources

bioRxiv2026

Color-dependent foraging in C. elegans integrates chromoprotein photosensitization with bacterial metabolic cues

Animals rely on color to navigate complex environments, yet how eyeless organisms use chromatic information to guide food choice remains poorly understood. Here, we show that Caenorhabditis elegans exhibits robust color dependent foraging driven by microbial chromophores, preferentially consuming red while avoiding blue chromoprotein expressing bacteria across bacterial backgrounds and wild isolates. This discrimination persists in darkness and independently of photoreceptor, revealing a mechanism beyond canonical photoreception. Purified chromoproteins and bacterial metabolite fractions independently reproduce preference, demonstrating complementary chromatic and post ingestive metabolic cues. Mechanistically, blue chromoproteins generate singlet oxygen, producing oxidative stress and remodeling bacterial tryptophan and pterin metabolism, whereas red food promotes serotonin production and feeding-associated neuropeptide signaling. Disrupting serotonin biosynthesis or neuropeptide processing abolishes color preference. Together, our findings reveal a previously unrecognized, novel sensory strategy in which wavelength-selective pigment photochemistry transforms microbial color into metabolic information that is integrated through gut brain neuroendocrine signaling to guide foraging behavior in an eyeless animal.

molecular biology↗

bioRxiv2025

Cyrene: A Novel Geroprotective Compound that Extends Lifespan and Healthspan in C. elegans and Drosophila

As aging is the primary risk factor for many chronic diseases, geroscience aims to target aging to delay age-related decline. Here, we identify Cyrene (dihydrolevoglucosenone), a sustainable, biocompatible solvent, as a novel geroprotective compound. Cyrene extends lifespan and healthspan in C. elegans, improving locomotor function and resistance to oxidative, thermal, osmotic, genotoxic, and proteotoxic stress. It also confers protection in neurodegenerative models of Alzheimers, Parkinsons, and Huntingtons disease. Cyrene is effective when delivered during development or early adulthood and requires administration before day 8 to extend longevity. Its benefits are independent of bacterial metabolism and partially independent of the FOXO transcription factor DAF-16. Importantly, Cyrene also extends lifespan and enhances oxidative stress resistance in Drosophila melanogaster, demonstrating cross-species efficacy. These findings identify Cyrene as a novel geroprotective compound that promotes longevity, resilience, and neuroprotection. Conservation across species supports future work to dissect molecular mechanisms and test its potential in mammals.

developmental biology↗

bioRxiv2025

Mutation of an insulin-sensitive Drosophila insulin-like receptor mutant requires methionine metabolism reprogramming to extend lifespan

Insulin/insulin growth factor signaling is a conserved pathway that regulates lifespan across many species. Multiple mechanisms are proposed for how this altered signaling slows aging. To elaborate these causes, we recently developed a series of Drosophila insulin-like receptor (dInr) mutants with single amino acid substitutions that extend lifespan but differentially affect insulin sensitivity, growth and reproduction. Transheterozygotes of canonical dInr mutants (Type I) extend longevity and are insulin-resistant, small and weakly fecund. In contrast, a dominant mutation (dInr353, Type II) within the Kinase Insert Domain (KID) robustly extends longevity but is insulin-sensitive, full-sized, and highly fecund. We applied transcriptome and metabolome analyses to explore how dInr353 slows aging without insulin resistance. Type I and II mutants overlap in many pathways but also produce distinct transcriptomic profiles that include differences in innate immune and reproductive functions. In metabolomic analyses, the KID mutant dInr353 reprograms methionine metabolism in a way that phenocopies dietary methionine restriction, in contrast to canonical mutants which are characterized by upregulation of the transsulfuration pathway. Because abrogation of S-adenosylhomocysteine hydrolase blocks the longevity benefit conferred by dInr353, we conclude the methionine cycle reprogramming of Type II is sufficient to slow aging. Metabolomic analysis further revealed the Type II mutant is metabolically flexible: unlike aged wildtype, aged dInr353 adults can reroute methionine toward the transsulfuration pathway, while Type I mutant flies upregulate the trassulfuration pathway continuously from young age. Altered insulin/insulin growth factor signaling has the potential to slow aging without the complications of insulin resistance by modulating methionine cycle dynamics. Author SummaryMutations in the invertebrate insulin/IGF signaling system robustly extend lifespan. Yet these interventions often cause insulin resistance, reduce growth, and impair fertility. In contrast, a dominant gain-of-function mutation in the kinase insert domain of the Drosophila insulin/IGF receptor extends lifespan while maintaining insulin sensitivity, growth, or reproduction. Here, we demonstrate this unique mutation reprograms methionine metabolism pathway in a way that mirrors dietary methionine restriction, which is known to extend lifespan in several animals including Drosophila and mice. Genetic epistasis analysis verifies this methionine cycle inhibition is an underlying cause for how the kinase insert domain mutation slows Drosophila aging while maintaining insulin-sensitivity, growth, and fecundity.

physiology↗