Project description:We performed microarrays to identify change of gene expression under NR, CR, and RM and found differentially expressed genes between each condition.
Project description:We used microarray analysis to further our understanding of the mode of action of the well know caloric restriction mimetic rapamycin and the compound Allantoin first studied in the context of aging in this study. His work helps build on our understanding of potential caloric restriction mimetics predicted from our bioinformatic aproach of quering the Connectivity Map, a database of drug-induced gene expression profiles, using the transcriptional profile of CR to identify drugs that induce a similar or opposite gene expression profile. Wild type worms of eat-2 mutants (a model of caloric restriction) were treated with the compounds of study with 2% DMSO or DMSO alone to serve as controls. All samples were peformed in triplicate.
Project description:Loss of protein homeostasis is one of the hallmarks of aging. As such, interventions that restore proteostasis should slow down the aging process and improve healthspan. Two of the most broadly used anti-aging interventions that are effective in organisms from yeast to mammals are calorie restriction (CR) and rapamycin (RM) treatment. To identify the regulatory mechanisms by which these interventions improve the protein homeostasis in the muscle, we carried out ribosome footprinting in the muscle from mice aged under standard conditions, or under long-term treatment with CR or RM. We found that RM primarily remodels the translation of upstream, and CR the translation of downstream, open reading frames (ORFs). Mass spectrometry analysis reveals the expression of numerous non-canonical ORFs at the protein level. These novel peptides may represent new targets for therapies aiming to maintain muscle function and extend healthspan.
Project description:We used microarray analysis to further our understanding of the mode of action of the well know caloric restriction mimetic rapamycin and the compound Allantoin first studied in the context of aging in this study. His work helps build on our understanding of potential caloric restriction mimetics predicted from our bioinformatic aproach of quering the Connectivity Map, a database of drug-induced gene expression profiles, using the transcriptional profile of CR to identify drugs that induce a similar or opposite gene expression profile.
Project description:As global life expectancy continues to climb, maintaining skeletal muscle function is increasingly essential to ensure a good life quality for aging populations. Calorie restriction (CR) is the most potent and reproducible intervention to extend health and lifespan, but is largely unachievable in humans. Therefore, identification of “CR mimetics” has received much attention. Since CR targets nutrient-sensing pathways centering on mTORC1, rapamycin, the allosteric inhibitor of mTORC1, has been proposed as a potential CR mimetic and counteracts age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Contrary to our prediction, long-term CR and rapamycin-treated geriatric mice display distinct skeletal muscle gene expression profiles despite both conferring benefits to aging skeletal muscle. Furthermore, CR improved muscle integrity in a mouse with nutrient-insensitive sustained muscle mTORC1 activity and rapamycin provided additive benefits to CR in aging mouse muscles. Therefore, RM and CR exert distinct, compounding effects in aging skeletal muscle, opening the possibility of parallel interventions to counteract muscle aging.
Project description:A Saccharomyces cerevisiae mutant with extended chronological life span was obtained by using an evolutionary engineering strategy, based on successive batch cultivation under gradually enhanced caloric restriction. The mutant strain SRM11 was selected which had about 50% longer life span than the reference strain. Whole-genome transcriptomic analysis of SRM11 with respect to the reference strain was performed to identify differences in gene expression levels between the two strains.
Project description:16 rats were mated and the dams continued pregnancy (controls) or were subsequently caloric restricted (CR) for 20% during days 1-12. Control female/male offspring continued normal lactation, while offspring of CR-treated dams received either normal lactation (CR group) or received during lactation until PN21 leptin supplementation. Leptin treatment of offspring during lactation after caloric restriction of dams during pregnancy reverts CR-induced dysfunction.
Project description:The effects of caloric restriction (CR) on glucose homeostasis and metabolic function differ between males and females. To investigate if hepatic function contributes to these sex differences, we collected liver samples from male and female C57BL/6NCrl mice that were fed ad libitum (AL) or underwent caloric restriction (CR; receiving 70% of daily AL intake) from 9-13 weeks of age. Livers were then analysed by bulk RNA-seq.
Project description:Comparison of transcriptional profiling in murine hearts obtained from the control mice fed ad libitium (AL) and treated with caloric restriction (CR). Comparison of transcriptional profiling in murine hearts obtained from cardiomyocye-specific Sirt1 knockout mice fed ad libitium and treated with caloric restriction.
