Biomedical subjects

Alexander A Soukas

Publications and source records attributed to Alexander A Soukas.

3 recordsLinked to original sources

PubMed2026

A lipid-sensitive food choice behavior influences aging outcomes from a longevity-promoting diet.

Organisms utilize sophisticated neurocircuitry to select optimal food sources. Methylobacterium is a lifespan-promoting diet for C. elegans that drives faster development and longevity; however, after ingestion, C. elegans consistently choose any other food option available. A screen for genetic regulators of this avoidance behavior toward Methylobacterium identified the AWB/AWC sensory neurons and the odr-1 guanylate cyclase expressed in those four ciliated neurons as mediators of the aversive response. Metabolic profiling of the Methylobacterium diet reveals enrichment for saturated fats, and here, we show that C. elegans sense and integrate signals related to these ingested lipids that subsequently cue food-related behaviors. Moreover, disruption of endogenous lipid metabolism modifies the intensity of the avoidance from Methylobacterium, suggesting the current state of lipid homeostasis influences food preference. Taken together, our work reveals that C. elegans modify food choice contemporaneously based in part on the chemosensory capacity to detect and utilize dietary lipids, which has longevity-promoting consequences.

AWB↗

PubMed2025

A consensus guide to preclinical indirect calorimetry experiments.

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data repository built on shared standards. This overdue initiative stands to markedly improve the accuracy and depth of efforts to interrogate mammalian metabolism. Data sharing according to established best practices will also accelerate the translation of basic findings into clinical applications for metabolic diseases afflicting global populations.

Calorimetry, Indirect↗

PubMed2025

Hormetic nutrient stress promotes longevity by orchestrating histone acetylation on key lipid catabolism and antioxidant defense genes.

Exposure to low levels of environmental challenges, known as hormetic stress, such as nutrient deprivation and heat shock, fosters subsequent stress resistance and promotes healthy aging in later life. However, specific mechanisms governing transcriptional reprogramming upon hormetic nutrient stress remain elusive. In this study, we identified histone H3 lysine 27 acetylation (H3K27ac) as a crucial driver of transcriptomic adaptation to hormetic fasting. Beyond its immediate function of enhancing lipid catabolism for alternative energy sources, stress-induced H3K27ac activates lifelong antioxidant defenses, thereby reducing reactive oxygen species (ROS) produced by stress-induced fatty acid oxidation and their accumulation during aging. The increase in H3K27ac, mediated by pioneer factor PHA-4/FOXA and cooperating transcription factor NHR-49/HNF4, is crucial for lifespan extension under hermetic nutrient stress in Caenorhabditis elegans. Our findings establish H3K27ac as a key transcriptional switch that bridges nutrient status with transcriptomic reprogramming, underpinning the pro-longevity effects of hormetic fasting through orchestrating lipid catabolism and antioxidative defenses.

Journal Article↗