Enabling Microglia to Better Clear Amyloid by Interfering in the LILRB4-APOE Interaction
Researchers here describe a mechanism that reduces the ability of microglia to ingest and clear misfolded amyloid-β, the protein aggregates associated with Alzheimer's disease. Interestingly, this involves APOE, and thus might be affected by the different APOE variants connected to Alzheimer's disease risk. The researchers demonstrate that interfering in the interaction between APOE and the LILRB4 receptor present on microglia can restore microglia-mediated clearance of amyloid-β.
Toxic clumps of brain proteins are features of many neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's dis...
Source: Fight Aging! - April 11, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
SENS Research Foundation and Lifespan.io to Merge
Merging the non-profits SENS Research Foundation and Lifespan.io is one of those ideas that makes a lot of sense in hindsight. SENS Research Foundation is research focused and very much interested in expanding into patient advocacy, as it depends on philanthropic funding. Lifespan.io is a patient advocacy organization that is very much interested into expanding into helping to advance the science of aging and clinical trials for therapies of aging. They complement one another, and may well produce greater gains as one organization than as two.
Lifespan.io, renowned for its unwavering advocacy for longevity and res...
Source: Fight Aging! - April 11, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Intermittent Methionione Restriction may be an Improvement on Continuous Methionine Restriction
Regulatory systems that detect low levels of the essential amino acid methionine are one of the more important triggers for the metabolic response to fasting and calorie restriction. Methionine is not manufactured in mammalian cells, can only be obtained from the diet, but is nonetheless essential for protein synthesis. Thus reducing only methionine levels in the diet can capture a sizable fraction of the benefits of calorie restriction.
While it is possible for a self-experimenter armed with time, a suitable database of methionine content by food type, and considerable willpower to practice significant levels of me...
Source: Fight Aging! - April 10, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
A Look at the Research Yet to be Accomplished for Cellular Senescence
In conclusion, although several clinical trials targeting SnCs are ongoing, various questions about the biology of SnCs remain open, resulting in a gap between molecular and cellular data. Concerning the need, initiatives such as SenNet aiming to create openly accessible atlases of SnCs should contribute enormously to the area. Advances in understanding the subcellular structure, the heterogeneity, and the dynamics of SnCs require the integration of molecular and cellular techniques with data analysis packages to evaluate high throughput evidence from microscopy and flow cytometry. It is also necessary to develop new equip...
Source: Fight Aging! - April 10, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Age-Related Changes in the Immune Response to Bone Injury
The aged immune system becomes consistently biased towards inflammation, existing in a state of constant low-grade unresolved inflammatory signaling. This changes cell behavior for the worse, and is disruptive to processes that require transient inflammation and participation of immune cells, such as regeneration following injury, or clearance of infectious pathogens. Here researchers discuss some of the details relating to the participation of the immune system in regeneration following bone injury. It is interesting to note the sizable differences between sexes, in addition to those introduced by aging.
Inflamma...
Source: Fight Aging! - April 10, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
LyGenesis Commences Phase II Trial for Growth of Liver Organoids in Patient Lymph Nodes
LyGenesis has been working towards liver organoid transplantation as a treatment for liver failure for some years now. Organs such as the liver, thymus, and a few others do not need to be in any specific place in the body to carry out many of their varied functions. Some of the vital work of the liver, for example, can be conducted in small organoids grown from liver cells transplanted into lymph nodes or other parts of the body that can act as stable bioreactors.
Even setting aside the possibility of growing functional liver organoids from patient cells or universal cell lines, it is worth noting that the old appro...
Source: Fight Aging! - April 9, 2024 Category: Research Authors: Reason Tags: Longevity Industry Source Type: blogs
Mitochondrial Hydrogen Peroxide Does Not Damage Nuclear DNA
In this study, we investigated the effects of H2O2 released by mitochondria or produced at the nucleosomes using a titratable chemogenetic approach. This enabled us to precisely investigate to what extent DNA damage occurs downstream of near- and supraphysiological amounts of localized H2O2.
Nuclear H2O2 gives rise to DNA damage and mutations and a subsequent p53 dependent cell cycle arrest. Mitochondrial H2O2 release shows none of these effects, even at levels that are orders of magnitude higher than what mitochondria normally produce. We conclude that H2O2 released from mitochondria is unlikely to directly damage ...
Source: Fight Aging! - April 9, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Cholesterol-Consuming Gut Microbes Lower Heart Disease Risk
Variations in the relative proportions of microbial species making up the gut microbiome apparently contribute to variations in LDL-cholesterol in the bloodstream. Lower LDL-cholesterol sustained over a lifetime produces a slower development of atherosclerotic plaque, and lower risk of consequent cardiovascular disease. While it seems likely there is no one optimal gut microbiome, there are certainly specific improvements that can be achieved for most older individuals. Fortunately, producing lasting changes in the balance of microbial populations making up the gut microbiome is an achievable goal. Fecal microbiota transpl...
Source: Fight Aging! - April 9, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Novel mTOR Inhibitors Viewed as a Safer Option by Conservative Investors
The safest sort of investment into therapeutic development is one made in a part of a field that is well established, producing a small variant of an existing drug, using the well beaten path of small molecule development, targeting a mechanism that is very well understood, and that has extensive safety data associated with it. One could argue that mTOR inhibition is the canonical example of a low risk investment in the longevity field. Like most lower-risk exercises in medical development, the potential gain for patients is modest. mTOR inhibition can produce larger gains in mouse life span than exercise, but doesn't beat...
Source: Fight Aging! - April 8, 2024 Category: Research Authors: Reason Tags: Longevity Industry Source Type: blogs
BHLHE40 and BHLHE41 Deletion May Make Macrophages and Microglia More Efficient
Macrophages in the body and microglia in the brain are similar forms of innate immune cell, responsible for clearing metabolic waste, among other duties. A number of age-related conditions involve the growing incapacity of macrophages or microglia, their transition to inflammatory states, and inability to clear debris and waste as they should. Atherosclerosis, for example, is arguably a condition caused by macrophage dysfunction, in which macrophages fail to clear excess cholesterol from blood vessel walls. Neurodegenerative conditions such as Alzheimer's disease, on the other hand, are characterized by the presence of act...
Source: Fight Aging! - April 8, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Dysfunction of the Glymphatic System Correlates with Faster Progression of Alzheimer's Disease
The glymphatic system is one of the pathways for drainage of cerebrospinal fluid from the brain to the body. This drainage is necessary to remove metabolic waste from the brain, and there is good evidence for reduced outflow of cerebrospinal fluid to lead to the development of neurodegenerative conditions. The work here adds to this body of evidence, showing that impaired flow of cerebrospinal fluid through the glymphatic system correlates with later severity of Alzheimer's disease.
The glymphatic system is an essential fluid-clearance system in the brain. The highly organized cerebrospinal fluid (CSF) transport s...
Source: Fight Aging! - April 8, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Fight Aging! Newsletter, April 8th 2024
In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth factors, cytoskeletal remodeling factors, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22-24 months) compared to saline-injected aged-matched controls.
Secretome delivery substantially increased whole-body lean mass and decreased fat mass, corresponding to higher myofiber cross-sectional area and smaller adipocyte size, respectively. Secretome-treated mice also had greater whole-bod...
Source: Fight Aging! - April 7, 2024 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs
Naked Mole Rats are Resistant to Ischemia, Such as Occurs Following a Heart Attack
On the one hand, naked mole-rats are most likely long-lived because they live underground, and thus suffer much lower rates of predation than other similarly sized mammals. Lower rates of extrinsic mortality appear to be a necessary prerequisite for the evolution of a longer species life span. On the other hand, living in a low-oxygen environment appears to have spurred the evolution of broad range of adaptations to that environment that incidentally happen to extend species longevity. Today's open access paper covers one aspect of those adaptations, a resistance to ischemia that reduces the harms resulting from the loss o...
Source: Fight Aging! - April 5, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Skin Biopsy as an Approach to Diagnose Parkinson's Disease
Researchers here demonstrate that the presence of phosphorylated α-synuclein in a skin biopsy is a good indicator of the presence of Parkinson's disease and other synucleinopathies. A skin biopsy is a more invasive procedure than most people want to undergo, but a greater ability to diagnose progressive diseases in their early stages will nonetheless tend to encourage the development of a greater ability to manage, treat, and avoid the later stages.
Affecting an estimated 2.5 million people in the United States, the synucleinopathies include Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple syst...
Source: Fight Aging! - April 5, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Transient Pockets of Hypoxia in the Mammalian Brain
Evidence suggests that the mammalian brain is operating at the very edge of its capacity, supplied with just enough oxygen and nutrients to barely get by. That exercise produces measurable short-term gains in cognitive function, while blood flow is increased, is one point in favor of this view. Another is provided here, in which researchers note that it is entirely normal to observe transient areas of hypoxia in the brain at rest, and that the occurrence of these regions is diminished by the increased blood flow of exercise. It is an open question as to what to do with this finding: we can imagine future technologies that ...
Source: Fight Aging! - April 5, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
