Reviewing Blood-Brain Barrier Dysfunction in the Context of Alzheimer's Disease
The biochemistry of the central nervous system is separated from the biochemistry of the rest of the body by the blood-brain barrier, a specialized lining of cells that wrap blood vessels that pass through the brain. Only some molecules and cells are permitted to pass into and out of the brain. Like all bodily systems, the blood-brain barrier breaks down with age, leading to leakage of unwanted molecules and cells into the brain, where they can provoke inflammation and dysfunction. This is thought to provide a significant contribution to the onset and further progression of age-related neurodegenerative conditions, given t...
Source: Fight Aging! - March 23, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Chromatin Regulation in the Mechanisms that Lead to Age-Related Inflammation
Chronic, unresolved, unprovoked inflammation is a feature of aging, a contributing cause of loss of tissue function and all of the common fatal age-related conditions. The biochemistry involved in the regulation of harmful age-related inflammatory signaling is complex, to say the least. There are many contributing causes, such as the signaling of senescent cells, the mislocalization of mitochondrial DNA resulting from mitochondrial dysfunction, and rising levels of other molecular debris from stressed and dying cells. How cells react in detail to inflammatory stimulation is far from fully understood. Researchers are intere...
Source: Fight Aging! - March 23, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

NT-3 Gene Therapy Improves Muscle Function in Old Mice
In this study, we used a triple muscle-specific creatine kinase (tMCK) promoter to restrict NT-3 expression to the skeletal muscle and self-complimentary adeno-associated virus serotype 1 (scAAV1) as vector. The treatment efficacy was assessed at 6 months post-injection using run to exhaustion and rotarod tests, in vivo muscle contractility assay, and histopathological studies of the peripheral nervous system, including NMJ connectivity and muscle. NT-3 gene therapy in WT-aged C57BL/6 mice resulted in functional and in vivo muscle physiology improvements, supported by quantitative histology from muscle, peripheral n...
Source: Fight Aging! - March 23, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, March 20th 2023
This study also provides the potential for de novo generation of complex organs in vivo. T Cells May Play a Role in the Brain Inflammation Characteristic of Neurodegenerative Conditions https://www.fightaging.org/archives/2023/03/t-cells-may-play-a-role-in-the-brain-inflammation-characteristic-of-neurodegenerative-conditions/ Alzheimer's disease, and other forms of neurodegenerative condition, are characterized by chronic inflammation in brain tissue. Unresolved inflammatory signaling is disruptive of tissue structure and function. Here, researchers provide evidence for T cells to become involved in thi...
Source: Fight Aging! - March 19, 2023 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Insulin Metabolism May Affect Life Span via Effects on Innate Immune Function
Insulin metabolism is one of the better studied areas of biochemistry in connection with aging, and one of the earliest areas of focus for the aging research community. Dysfunction of insulin metabolism, meaning loss of insulin sensitivity, is characteristic of obesity and the slide into type 2 diabetes, and the manifestations of diabetes in some ways resemble accelerated aging. While one should not consider high levels of a single form of dysfunction to be accelerated aging, since normal aging is a specific mix of various forms of damage and dysfunction, it can be worth bearing in mind that there are mechanistic overlaps ...
Source: Fight Aging! - March 17, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

A Tyrosine Kinase Inhibitor Produces Improvement in Early Stage Alzheimer's Patients
Senolytic drugs are those that selectively force senescent cells into programmed cell death. Senescent cells accumulate with age throughout the body, and their pro-inflammatory signaling is disruptive to tissue structure and function when maintained over the long term. Clearance of senescent cells has produced sizable, rapid reversal of age-related disease and improvement in health in mice. There are numerous classes of senolytic small molecule drugs, each class attacking the biochemistry of senescent cells from a different direction in order to force programmed cell death. The well-studied senolytic drug dasatinib is a ty...
Source: Fight Aging! - March 16, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Reprogramming Tumor Cells into Antigen-Presenting Cells
Today's research materials describe a clever approach to cancer immunotherapy, focused on the goal of enabling the immune system to better identify cancerous cells. In the past, researchers have made some inroads in training the immune system to attack specific target molecules characteristic of cancerous cells, but this is a slow and expensive process when progressing from single target to single target. Further, any given cancer might be capable of evolving to function without exhibiting any one specific target molecule, and only some cancers of a particular type will exhibit that specific signature molecule to start wit...
Source: Fight Aging! - March 13, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

More on Transcriptional Noise in Aging
As a companion piece to a recent article questioning whether transcriptional noise actually exists as envisaged, this review paper covers what is known and unknown in this part of the field. Transcriptional noise is random variation in the first stage of gene expression, and it is thought to increase with age. It seems likely to be a consequence of the broad variety of changes and dysfunctions that occur in cellular biochemistry in old tissues, an accompaniment to faltering quality control of protein synthesis and altered epigenetics. While easily defined at the high level, transcriptional noise is challenging to measure i...
Source: Fight Aging! - March 13, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Launching Biomedical Careers for Students Who Are Deaf and Hard of Hearing
Group of RIT U-RISE students, including Bo Allaby (standing second from the right) and Maameyaa Asiamah (kneeling in front) who are interviewed in this post. Credit: Dr. Bonnie Jacob. Scientists who are deaf and hard of hearing (DHH) are underrepresented at all career stages, especially at the Ph.D. level. To address this, the Undergraduate Research Training Initiative for Student Enhancement (U-RISE) training program for undergraduates who are deaf and hard of hearing at the Rochester Institute of Technology (RIT) in Rochester, New York, has committed to lifting barriers and increasing DHH representation in science. ...
Source: Biomedical Beat Blog - National Institute of General Medical Sciences - March 8, 2023 Category: Research Authors: Chrissa Chverchko Tags: Being a Scientist Profiles Training Source Type: blogs

Fight Aging! Newsletter, March 6th 2023
In this study, we develop a rFOXN1 fusion protein that contains the N-terminal of CCR9, FOXN1, and TAT. We show here that, when injected intravenously (i.v.) into aged mice, the rFOXN1 fusion protein can migrate into the thymus and enhance T cell generation in the thymus, resulting in increased number of peripheral T cells. Our results suggest that the rFOXN1 fusion protein has the potential to be used in preventing and treating T cell immunodeficiency in the older adult. Increased miR-181a-5p Expression Improves Neural Stem Cell Activity, Learning, and Memory in Old Mice https://www.fightaging.org/archives/20...
Source: Fight Aging! - March 5, 2023 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Considering Proteostasis and Aging
Proteostasis is the normal maintenance of protein levels and protein structure in a cell. This is disrupted with age, the result of failing quality control, epigenetic change, and other issues. Loss of proteostasis is a hallmark of aging, but has the look of a consequence of aging, not a cause to be addressed. It is also highly complex, and thus progress towards practical therapies is probably better served by a focus on causes of aging rather than the fine details of age-related changes in the cell. Fix the causes, see how well those repair efforts improve long-term health, and then worry about the fine details of the bio...
Source: Fight Aging! - March 3, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Innovating Education, Outreach, and Mentorship With Organic Chemist Neil Garg
Dr. Neil Garg. Credit: Penny Jennings. “An important part of being in science is being in a community,” says Neil Garg, Ph.D., Distinguished Professor and chair of the department of chemistry and biochemistry at the University of California Los Angeles (UCLA). That philosophy has led him to prioritize mentorship, diversity, and inclusion—while maintaining research excellence—as well as re-envisioning what it means to educate students and the public. Falling in Love With Chemistry Science was always a part of Dr. Garg’s childhood. He participated in science fairs as a kid but says he did it for the commun...
Source: Biomedical Beat Blog - National Institute of General Medical Sciences - March 1, 2023 Category: Research Authors: Chrissa Chverchko Tags: Being a Scientist Chemistry, Biochemistry and Pharmacology Profiles Training Source Type: blogs

Biochemical Differences Between the Response to High Intensity versus Moderate Exercise
In this study, we asked the question whether the cellular senescence-lowering effect of exercise in human skeletal muscle can occur only at the intensity sufficient to induce DNA damage and inflammation. Biopsied vastus lateralis of 9 sedentary men (age 26.1 ± 2.5 y) were assessed before and after a single bout of moderate steady state exercise (SSE, 60% maximal aerobic power) and high intensity interval exercise (HIIE, 120% maximal aerobic power). Increases in cell infiltration (+1.2 folds), DNA strand break (+1.3 folds), and γ-H2AX+ myofibers (+1.1 folds) occurred immediately after HIIE and returned to baseline in 24 h...
Source: Fight Aging! - February 27, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, February 27th 2023
This study tested the hypothesis that ischemic vascular repair in aging by Ang-(1-7) involves attenuation of myelopoietic potential in the bone marrow and decreased mobilization of inflammatory cells. Young or Old male mice of age 3-4 and 22-24 months, respectively, received Ang-(1-7) for four weeks. Myelopoiesis was evaluated in the bone marrow (BM) cells by carrying out the colony forming unit (CFU-GM) assay followed by flow cytometry of monocyte-macrophages. Expression of pro-myelopoietic factors and alarmins in the hematopoietic progenitor-enriched BM cells was evaluated. Hindlimb ischemia (HLI) was induced by ...
Source: Fight Aging! - February 26, 2023 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

How Important is the Error Rate in Protein Synthesis to the Pace of Aging?
Cellular biochemistry is a messy process, a soup of colliding molecules moving at high speed and reacting with one another. Within this soup, complex processes of assembly and interaction take place. The blueprints of genes in DNA are converted into RNA via one complicated set of reading and assembly mechanisms in the cell nucleus. That RNA exits the nucleus and is then processed in ribosomes to produce proteins from amino acid fragments. Proteins are then folded in to the correct shape in the endoplasmic reticulum, and then must further be transported to a final destination within the cell. All of this takes place ...
Source: Fight Aging! - February 23, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs