Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging.

Epigenetic alterations and metabolic dysfunction are two hallmarks of aging. However, the mechanism of how their interaction regulates aging, particularly in mammals, remains largely unknown. Here we show ELOVL fatty acid elongase 2 (Elovl2), a gene whose epigenetic alterations are most highly correlated with age prediction, contributes to aging by regulating lipid metabolism.

Pharmacological Perturbation of Mechanical Contractility Enables Robust Transdifferentiation of Human Fibroblasts into Neurons.

Direct cell reprogramming, also called transdifferentiation, is valuable for cell fate studies and regenerative medicine. Current approaches to transdifferentiation are usually achieved by directly targeting the nuclear functions, such as manipulating the lineage-specific transcriptional factors, microRNAs, and epigenetic modifications. Here, a robust method to convert fibroblasts to neurons through targeting the cytoskeleton followed by exposure to lineage-specification surroundings is reported.

Pharmacological regulation of tissue fibrosis by targeting the mechanical contraction of myofibroblasts.

Fibrosis can occur in almost all tissues and organs and affects normal physiological function, which may have serious consequences, such as organ failure. However, there are currently no effective, broad-spectrum drugs suitable for clinical application. Revealing the process of fibrosis is an important prerequisite for the development of new therapeutic targets and drugs.

Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions.

Unisexual reproduction is widespread among lower vertebrates, but not in mammals. Deletion of the H19 imprinted region in immature oocytes produced bimaternal mice with defective growth; however, bipaternal reproduction has not been previously achieved in mammals. We found that cultured parthenogenetic and androgenetic haploid embryonic stem cells (haESCs) display DNA hypomethylation resembling that of primordial germ cells.

Generation of Mouse Haploid Somatic Cells by Small Molecules for Genome-wide Genetic Screening.

The recent success of derivation of mammalian haploid embryonic stem cells (haESCs) has provided a powerful tool for large-scale functional analysis of the mammalian genome. However, haESCs rapidly become diploidized after differentiation, posing challenges for genetic analysis. Here, we show that the spontaneous diploidization of haESCs happens in metaphase due to mitotic slippage.

Leucine supplementation improves leptin sensitivity in high-fat diet fed rats.

Background: Several studies have reported the favorable effect of leucine supplementation on insulin resistance or insulin sensitivity. However, whether or not leucine supplementation improves leptin sensitivity remains unclear.

Design: Forty-eight male Sprague-Dawley rats were fed with either a high-fat diet (HFD) or HFD supplemented with 1.