Search bioRxiv⌕ Search

Biology subjects

Parish, A.

Publications and source records attributed to Parish, A..

2 recordsLinked to original sources
bioRxiv2025

Adaptive thermogenesis reprograms the behavioural and metabolic responses to protein restriction for successful amino acid homeostasis

Reduced protein intake is proposed to contribute to the obesity epidemic, but existing murine models of protein restriction do not promote obesity, limiting insight into underlying mechanisms. Here we show that mice self-select a consistent daily protein intake, independent of energy needs. Under mild protein restriction (7-10% protein), mice exhibit hyperphagia and increased adiposity. This hyperphagic response is blunted at thermoneutrality, leading to loss of lean mass and body weight. Protein-restricted mice also fail to exhibit protein preference at thermoneutrality, despite elevated circulating FGF21 levels. Circulating levels of essential amino acids (AAs) are tightly regulated during protein restriction at 22{degrees}C, but this regulation is lost at 28{degrees}C. Metabolomic and transcriptional analyses revealed a role for hepatic and brown fat AA-derived acylcarnitines and N-acetyl AAs in buffering free AA levels for the maintenance of AA homeostasis at 22{degrees}C, but these pathways are blunted at thermoneutrality. Thus, the behavioural and metabolic adaptations to protein restriction rely on coordinated peripheral and central mechanisms, modulated by ambient temperature. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=63 SRC="FIGDIR/small/667623v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1d1a9e1org.highwire.dtl.DTLVardef@1e7f3b5org.highwire.dtl.DTLVardef@131276borg.highwire.dtl.DTLVardef@130757_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗
bioRxiv2025

Reporting quality, effect sizes, and biases for aging interventions: a methodological appraisal of the DrugAge database

Though interest has grown significantly over the past decades in interventions that may slow the aging process, most evidence for these interventions still comes from experiments in non-human animals. These studies may suffer from design, quality and reporting issues. The quality and reporting of preclinical studies have not yet been studied systematically in anti-aging research. Here we analyzed the DrugAge database, assessing reporting study quality, bias and effect sizes across 667 anti-aging preclinical studies. We found significant shortcomings in reporting of crucial design features such as randomization and blinding, as well as large variation in reporting quality and effects across species. Non-mammal findings typically did not translate to mammals. Although anti-aging interventions may have different effects depending on when they are started, most studies began giving the intervention under investigation very early in the organisms lifespan. Our findings suggest there is substantial room for improvement in preclinical anti-aging research.

physiology↗