Effects of high fat diet on metabolic health vary by age of menopause onset.

Menopause accelerates metabolic dysfunction, including (pre-)diabetes, obesity and visceral adiposity. However, the effects of endocrine vs. chronological aging in this progression are poorly understood.

Treatment with brain specific estrogen prodrug ameliorates cognitive effects of surgical menopause in mice.

Menopause is an endocrine shift leading to increased vulnerability for cognitive impairment and dementia risk factors, in part due to loss of neuroprotective circulating estrogens. Systemic replacement of estrogen post-menopause has limitations, including risk for estrogen-sensitive cancers. A promising therapeutic approach therefore might be to deliver estrogen only to the brain.

Effects of High Fat Diet on Metabolic Health Vary by Age of Menopause Onset.

Menopause accelerates metabolic dysfunction, including (pre-)diabetes, obesity and visceral adiposity. However, the effects of endocrine vs. chronological aging in this progression are poorly understood.

Brain Specific Estrogen Ameliorates Cognitive Effects of Surgical Menopause in Mice.

Menopause is a major endocrinological shift that leads to an increased vulnerability to the risk factors for cognitive impairment and dementia. This is thought to be due to the loss of circulating estrogens, which exert many potent neuroprotective effects in the brain. Systemic replacement of estrogen post-menopause has many limitations, including increased risk for estrogen-sensitive cancers.

Sex differences in the effects of high fat diet on underlying neuropathology in a mouse model of VCID.

Background: Damage to the cerebral vasculature can lead to vascular contributions to cognitive impairment and dementia (VCID). A reduction in blood flow to the brain leads to neuropathology, including neuroinflammation and white matter lesions that are a hallmark of VCID. Mid-life metabolic disease (obesity, prediabetes, or diabetes) is a risk factor for VCID which may be sex-dependent (female bias).

Epigenetic regulation of T cell development.

Epigenetic regulators are pivotal factors that influence and control T cell development. Recent findings continue to reveal additional elements of epigenetic modifications that play significant and crucial roles at different stages of T cell development. Through gaining a better understanding of the various epigenetic factors that influence the formation and survival of maturing T cells, new therapies can potentially be developed to combat diseases caused by dysregulated epigenetic chromatin modifications.

New Insights into Epigenetic Regulation of T Cell Differentiation.

Immature CD4 CD8 thymocytes progress through several developmental steps in the thymus, ultimately emerging as mature CD4 (helper) or CD8 (cytotoxic) T cells. Activation of naïve CD4 and CD8 T cells in the presence of specific cytokines results in the induction of transcriptional programs that result in their differentiation into effector or memory cells and in the case of CD4 T cells, the adoption of distinct T-helper fates. Previous studies have shown that histone modification and DNA methylation play important roles in each of these events.

The histone demethylase Lsd1 regulates multiple repressive gene programs during T cell development.

Analysis of the transcriptional profiles of developing thymocytes has shown that T lineage commitment is associated with loss of stem cell and early progenitor gene signatures and the acquisition of T cell gene signatures. Less well understood are the epigenetic alterations that accompany or enable these transcriptional changes. Here, we show that the histone demethylase Lsd1 (Kdm1a) performs a key role in extinguishing stem/progenitor transcriptional programs in addition to key repressive gene programs during thymocyte maturation.