Biology subjects

Lu, Y.-X.

Publications and source records attributed to Lu, Y.-X..

4 recordsLinked to original sources

bioRxiv2022

Full geroprotection from brief rapamycin treatment by persistently increased intestinal autophagy

The licensed drug rapamycin has potential to be repurposed for geroprotection. A key challenge is to avoid adverse side-effects from continuous dosing regimes. Here we show a profound memory effect of brief, early rapamycin treatment of adults, which extended lifespan in Drosophila to the same degree as lifelong dosing. Lasting memory of earlier rapamycin treatment was mediated by elevated autophagy in enterocytes of the gut, accompanied by increased levels of intestinal lysosomal alpha-mannosidase V (LManV), proteins involved in branched-chain amino acid metabolism and lysozyme levels, and by maintained structure and function of the ageing intestine. Brief elevation of autophagy in early adulthood itself induced a long-term increase in autophagy. In mice, a short-term, 3-month treatment in early adulthood also induced a memory effect, with maintenance similar to that seen with chronic treatment, of lysozyme distribution, Man2B1 level in intestinal crypts, Paneth cell architecture and gut barrier function, even 6 months after rapamycin was withdrawn. The geroprotective effects of chronic rapamycin treatment can thus be obtained with a brief pulse of the drug in early adulthood.

physiology↗

bioRxiv2021

Sexual identity of enterocytes regulates rapamycin-mediated intestinal homeostasis and lifespan extension

Pharmacological attenuation of mTOR by rapamycin and other compounds presents a promising route for delay of ageing-related pathologies, including intestinal cancers. Here, we show that rapamycin treatment in Drosophila extends lifespan in females but not in males. Female-specific, age-related gut pathology and impaired intestinal barrier function are both markedly slowed by rapamycin treatment, mediated by increased autophagy. Upon rapamycin treatment, female intestinal enterocytes increase autophagy, via the H3/H4 histone-Bchs axis, while male enterocytes show high basal levels of autophagy that do not increase further upon rapamycin treatment. Sexual identity of enterocytes alone, determined by the expression of transformerFemale, dictates sexually dimorphic cell size, H3/H4-Bchs expression, basal rates of autophagy, fecundity, intestinal homeostasis and extension of lifespan in response to rapamycin. This study highlights that tissue sex determines regulation of metabolic processes by mTOR and the efficacy of mTOR-targeted, anti-ageing drug treatments.

physiology↗

bioRxiv2020

Demographics and Employment of Max-Planck Society's Postdocs

The recently founded Max Planck PostdocNet brings together postdoctoral researchers (or postdocs) from the Max Planck Society (MPS), provides representation for the postdoctoral community across all Max Planck Institutes (MPI) and associated institutes, and advocates for their interests on their behalf. At the 2019 founding meeting, MPS postdocs quickly raised their concerns about their employment situation and their associated social and working conditions. Subsequently, the PostdocNet conducted the first survey targeting exclusively postdoctoral researchers to gather information on their demographics, employment situations and social conditions. This report presents the results of this survey, providing a thorough characterization of the postdoc demographics as well as the working conditions experienced by the postdoctoral community of the MPS. Remarkably, the survey analysis revealed a number of disparities in the access to employment type, wage level and social benefits. These results will guide future and present MPS postdoctoral researchers and their employers at the MPS to thrive for equality and fairness. Moreover, these results should be of help to the MPS to establish, improve and maintain optimal working conditions for MPS postdocs.

scientific communication and education↗

bioRxiv2018

Ras inhibition by trametinib treatment in Drosophila attenuates gut pathology in females and extends lifespan in both sexes

Females of most species live longer than do males. Furthermore, lifespan-extending interventions in laboratory model organisms are often more effective in females (Regan and Partridge 2013). For instance, genetic and pharmacological suppression of activity of the insulin/insulin-like signalling - target of rapamycin (IIS-TOR) network generally extends female lifespan more than that of males in both Drosophila and mice (Clancy et al. 2001; Selman et al. 2009). We previously showed that attenuation of Ras-dependent IIS signalling by treatment with the FDA-approved MEK inhibitor, trametinib extends lifespan in females (Slack et al. 2015). Here, we demonstrate that trametinib treatment has beneficial effects on female-specific, age-related gut pathologies, similar to those obtained through dietary restriction (Regan et al. 2016). Importantly, we identify Ras inhibition as an effective lifespan-extending manipulation in males as well as females, pointing to parallel mechanisms of lifespan extension by trametinib in both sexes.

physiology↗