Heterochronic Plasma Transfer: Experimental Design, Considerations, and Technical Challenges.

Experimental approaches such as Heterochronic Plasma Transfer (HPT) provide insights into the aging process and help identify the factors that impact aging, with the aim of developing anti-aging therapies. HPT involves the transfer of plasma from an animal of one age to an animal of a different age and highlights the effects of the systemic environment on aging. Despite its importance as an aging research tool, HPT is not without limitations and HPT experiments across various studies differ in key experimental designs considerations, presenting a challenge in obtaining comparable outcomes.

Role of Estrogen Receptor α in Aging and Chronic Disease.

Estrogen receptor alpha (ERα) plays a crucial role in reproductive function in both sexes. It also mediates cellular responses to estrogens in multiple nonreproductive organ systems, many of which regulate systemic metabolic homeostasis and inflammatory processes in mammals. The loss of estrogens and/or ERα agonism during aging is associated with the emergence of several comorbid conditions, particularly in females undergoing the menopausal transition.

Microglial MHC-I induction with aging and Alzheimer's is conserved in mouse models and humans.

Major histocompatibility complex I (MHC-I) CNS cellular localization and function is still being determined after previously being thought to be absent from the brain. MHC-I expression has been reported to increase with brain aging in mouse, rat, and human whole tissue analyses, but the cellular localization was undetermined. Neuronal MHC-I is proposed to regulate developmental synapse elimination and tau pathology in Alzheimer's disease (AD).

Differential usage of DNA modifications in neurons, astrocytes, and microglia.

Background: Cellular identity is determined partly by cell type-specific epigenomic profiles that regulate gene expression. In neuroscience, there is a pressing need to isolate and characterize the epigenomes of specific CNS cell types in health and disease. This is especially true as for DNA modifications where most data are derived from bisulfite sequencing that cannot differentiate between DNA methylation and hydroxymethylation.

Metabolic benefits of 17α-estradiol in liver are partially mediated by ERβ in male mice.

Metabolic dysfunction underlies several chronic diseases. Dietary interventions can reverse metabolic declines and slow aging but remaining compliant is difficult. 17α-estradiol (17α-E2) treatment improves metabolic parameters and slows aging in male mice without inducing significant feminization.

A single-cell atlas of the aging murine ovary.

Ovarian aging leads to diminished fertility, dysregulated endocrine signaling, and increased chronic disease burden. These effects begin to emerge long before follicular exhaustion. Around 35 years old, women experience a sharp decline in fertility, corresponding to declines in oocyte quality.

Metabolic benefits of 17α-estradiol in liver are partially mediated by ERβ in male mice.

Metabolic dysfunction underlies several chronic diseases. Dietary interventions can reverse metabolic declines and slow aging but remaining compliant is difficult. 17α-estradiol (17α-E2) treatment improves metabolic parameters and slows aging in male mice without inducing significant feminization.

Microglial senescence contributes to female-biased neuroinflammation in the aging mouse hippocampus: implications for Alzheimer's disease.

Background: Microglia, the brain's principal immune cells, have been implicated in the pathogenesis of Alzheimer's disease (AD), a condition shown to affect more females than males. Although sex differences in microglial function and transcriptomic programming have been described across development and in disease models of AD, no studies have comprehensively identified the sex divergences that emerge in the aging mouse hippocampus. Further, existing models of AD generally develop pathology (amyloid plaques and tau tangles) early in life and fail to recapitulate the aged brain environment associated with late-onset AD.

Microglial MHC-I induction with aging and Alzheimer's is conserved in mouse models and humans.

Major Histocompatibility Complex I (MHC-I) CNS cellular localization and function is still being determined after previously being thought to be absent from the brain. MHC-I expression has been reported to increase with brain aging in mouse, rat, and human whole tissue analyses but the cellular localization was undetermined. Neuronal MHC-I is proposed to regulate developmental synapse elimination and tau pathology in Alzheimer's disease (AD).

Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome.

Assessing cell-type-specific epigenomic and transcriptomic changes are key to understanding ovarian aging. To this end, the optimization of the translating ribosome affinity purification (TRAP) method and the isolation of nuclei tagged in specific cell types (INTACT) method was performed for the subsequent paired interrogation of the cell-specific ovarian transcriptome and epigenome using a novel transgenic NuTRAP mouse model. The expression of the NuTRAP allele is under the control of a floxed STOP cassette and can be targeted to specific ovarian cell types using promoter-specific Cre lines.

Non-Small Cell Lung Cancer Presenting as Anterior Nasal Mass and Epistaxis.

Lung malignancy presentation with an uncommon metastatic site is a diagnostic challenge and often associated with poor prognosis. Nasal cavity is a rare metastatic site for any type of lung cancer. We report an unusual case of poorly differentiated adenosquamous carcinoma of the lung with widespread metastasis presenting as a right vestibular nasal mass with epistaxis.

Assessing tolerability and physiological responses to 17α-estradiol administration in male rhesus macaques.

17α-estradiol has recently been shown to extend healthspan and lifespan in male mice through multiple mechanisms. These benefits occur in the absence of significant feminization or deleterious effects on reproductive function, which makes 17α-estradiol a candidate for translation into humans. However, human dosing paradigms for the treatment of aging and chronic disease are yet to be established.

Chromosomal and gonadal factors regulate microglial sex effects in the aging brain.

Biological sex contributes to phenotypic sex effects through genetic (sex chromosomal) and hormonal (gonadal) mechanisms. There are profound sex differences in the prevalence and progression of age-related brain diseases, including neurodegenerative diseases. Inflammation of neural tissue is one of the most consistent age-related phenotypes seen with healthy aging and disease.

Long-term methamphetamine self-administration increases mesolimbic mitochondrial oxygen consumption and decreases striatal glutathione.

Neurotoxic regimens of methamphetamine (METH) are known to increase reactive oxygen species (ROS), affect redox homeostasis, and lead to damage in dopamine neurons. Functional changes induced by long-term METH self-administration on mitochondrial respiratory metabolism and redox homeostasis are less known. To fill this gap, we implanted a jugular catheter into adult male mice and trained them to nose poke for METH infusions.

17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice.

Estrogen signaling is protective against chronic liver diseases, although men and a subset of women are contraindicated for chronic treatment with 17β-estradiol (17β-E2) or combination hormone replacement therapies. We sought to determine if 17α-estradiol (17α-E2), a naturally occurring diastereomer of 17β-E2, could attenuate liver fibrosis. We evaluated the effects of 17α-E2 treatment on collagen synthesis and degradation rates using tracer-based labeling approaches in male mice subjected to carbon tetrachloride (CCl)-induced liver fibrosis.

Translatomic response of retinal Müller glia to acute and chronic stress.

Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes.

Developmental or adult-onset deletion of neurotensin receptor-1 from dopamine neurons differentially reduces body weight.

Central neurotensin signaling via neurotensin receptor-1 (NtsR1) modulates various aspects of physiology, including suppressing feeding and promoting locomotor activity that can support weight loss. However, it remains unclear when and where NtsR1 expression contributes to control of body weight vs. other effects.

Impact of Adherence with Disease-Modifying Therapies on All-Cause Mortality Rates Among Veterans with Multiple Sclerosis.

BACKGROUND Adherence to disease-modifying therapies (DMTs) is essential for reducing multiple sclerosis (MS)-related relapses and disability. However, no known data exist regarding rates of adherence to DMTs and their impact on mortality. The present study aimed to determine the effect of adherence to DMTs on all-cause mortality in patients with MS in a real-world setting.

Differential Regulation of Mouse Hippocampal Gene Expression Sex Differences by Chromosomal Content and Gonadal Sex.

Common neurological disorders, like Alzheimer's disease (AD), multiple sclerosis (MS), and autism, display profound sex differences in prevalence and clinical presentation. However, sex differences in the brain with health and disease are often overlooked in experimental models. Sex effects originate, directly or indirectly, from hormonal or sex chromosomal mechanisms.

Minimizing the Confounds of Cell-Isolation Techniques on Transcriptomic and Translatomic Profiles of Purified Microglia.

Modern molecular and biochemical neuroscience studies require analysis of specific cellular populations derived from brain tissue samples to disambiguate cell type-specific events. This is particularly true in the analysis of minority glial populations in the brain, such as microglia, which may be obscured in whole tissue analyses. Microglia have central functions in development, aging, and neurodegeneration and are a current focus of neuroscience research.

The Impact of Adherence to Disease-Modifying Therapies on Functional Outcomes in Veterans with Multiple Sclerosis.

Background: Patients who adhere to their DMTs have lower rate of MS-related relapses and disability.

Objective: We sought to determine the adherence rate to disease-modifying therapies (DMTs) and its impact on functional outcome(s) in veterans with multiple sclerosis (MS).

Method: We reviewed the electronic records of 279 veterans with MS who were periodically followed in our MS clinic.

Impact of adherence to disease-modifying therapies on employment among veterans with multiple sclerosis.

Purpose: Patients who adhere to their disease-modifying therapies (DMTs) have a lower rate of MS-related relapses and disability. We sought to determine the adherence rate to DMTs and the association between adherence to DMTs and employment in patients with multiple sclerosis (MS).

Method: One hundred and forty-two patients with MS who were periodically followed in our clinic between January 2000 and January 2020.