The Challenges Inherent in Understanding a Fast-Moving, Developing Field
This messy popular science article is an essay length expression of futility on the part of a journalist who accepts that he is not equipped to understand the field of aging research and the longevity industry that has arisen in the past decade. One can talk to the talking heads, but they will all say something different. One can look for proof of efficacy for specific approaches, and find only contradictory data, or only compelling animal data, or only small effect sizes, and a lack of the sort of certainty that arises from large human trials. Those trials are still in the future for near every approach to the treatment o...
Source: Fight Aging! - April 25, 2024 Category: Research Authors: Reason Tags: Healthy Life Extension Community Source Type: blogs

The Rodent Aging Interventions Database
You might compare the LEV Foundation's Rodent Aging Interventions Database with the DrugAge database, both emerging from the efforts of researchers who found themselves frequently reviewing the existing literature on age-slowing interventions in animal models. One of the things to bear in mind about the existing literature is that rodent studies that show an apparent modest slowing of aging frequently fail to replicate when later investors take a more rigorous approach, with larger numbers of mice. The history of the NIA Interventions Testing Program is largely a repeated demonstration of this point. The Rodent Ag...
Source: Fight Aging! - April 25, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

The Role of Immune Aging in Neurodegenerative Conditions
The research community has come to see chronic inflammation and other age-related immune system dysfunctions as an important aspect of neurodegenerative conditions. Inflammation in the short term is necessary for defense against pathogens and regeneration following injury. Unresolved, constant inflammation is harmful to tissue structure and function, however, changing cell behavior for the worse. In brain tissue, the effects of inflammatory signaling on the behavior of innate immune cells called microglia appears particularly important. Neurogenerative conditions are characterized by activated microglia. These microglia ar...
Source: Fight Aging! - April 23, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Investigating the Mechanisms of Very Early Alzheimer's Disease
Researchers here look at cellular dysfunction that may form the earliest stages of Alzheimer's disease, prior to the accumulation of misfolded amyloid-β and cognitive decline. In general, intervening early in the progression of a disease will always be easier, given the right target. The challenge lies in identifying and understanding the causative mechanisms, in an environment in which (a) there is little access to brain tissue in the earliest stages of Alzheimer's disease, and (b) the animal models are highly artificial, as mice do not normally develop anything resembling Alzheimer's disease, and thus may not accurately...
Source: Fight Aging! - April 23, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, April 22nd 2024
This study reveals a potential treatment for human mitochondrial diseases. « Back to Top A Population Study Correlates Air Pollution with Faster Cognitive Aging https://www.fightaging.org/archives/2024/04/a-population-study-correlates-air-pollution-with-faster-cognitive-aging/ A number of large epidemiological studies provide evidence for long-term exposure to greater levels of air pollution to accelerate the onset and progression of age-related disease. A few of these manage to control for the tendency for wealthier people to avoid living in areas with higher particulate air pollution, ...
Source: Fight Aging! - April 21, 2024 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Parkinson's Disease in the SENS View of Damage Repair
The Strategies for Engineered Negligible Senescence (SENS) is a view of aging as accumulated damage. Drawing from the extensive scientific literature on aging, the originators of SENS created an outline of the forms of cell and tissue damage that are fundamental causes of aging, in that they occur as a natural side-effect of the normal operation of our cellular biochemistry. So we might consider the loss of vital cells due to declining stem cell function, mutations to nuclear DNA and mitochondrial DNA, cross-linking of vital molecules in the extracellular matrix, accumulated metabolic waste in long-lived cells, generation ...
Source: Fight Aging! - April 19, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Herpes Simplex Infection Correlates with Amyloid Burden in the Aging Brain
There is a continuing debate over the degree to which Alzheimer's is driven by persistent infection in brain tissue, such as by varieties of herpesvirus. Amyloid-β is an antimicrobial peptide, a part of the innate immune response, and one could argue that persistently raised expression of amyloid-β will increase misfolding and generation of the aggregates that drive pathology in the early stages of Alzheimer's disease, at least under the amyloid cascade hypothesis. The data is not all convincing, however, which suggests that perhaps there are other factors involved - that multiple viruses interact in some people, for exa...
Source: Fight Aging! - April 15, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, April 15th 2024
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 14, 2024 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

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

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

Does Herpes Simplex Virus cause Alzheimer ’ s Disease?
by Gertrud U. Rey Alzheimer’s Disease (AD) is a neurodegenerative disorder and the most common form of dementia. Although its exact cause is unclear, an increasing body of evidence suggests that an infection with herpes simplex virus (HSV) may contribute to onset of AD later in life. Both types of HSV (HSV-1 and HSV-2) infect … Does Herpes Simplex Virus cause Alzheimer’s Disease? Read More » (Source: virology blog)
Source: virology blog - April 4, 2024 Category: Virology Authors: Gertrud U. Rey Tags: Basic virology Gertrud Rey alzheimer's disease amyloid beta amyloid plaque APOE-ɛ4 association causation cognitive defect cognitive function correlation dementia herpes simplex virus herpes simplex virus 1 herpesvirus mechan Source Type: blogs

Using mRNA to Generate Therapeutic Antibodies in the Brain
It may turn out to be cost-effective to replace delivery of therapeutic monoclonal antibodies with delivery of messenger RNA (mRNA), encapsulated in a lipid nanoparticle or linked to a cell penetrating molecule of some sort in order to reach the desired tissues and be taken up into the cytoplasm. Researchers here consider this in the context of treating Alzheimer's disease, where the primary thrust of therapeutic development involves the use of antibodies targeting the various protein aggregates thought to contribute to disease progression. Monoclonal antibodies have emerged as a leading therapeutic agent for the ...
Source: Fight Aging! - April 4, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Dephosphorylation-Targeting Chimeras to Clear Tau Aggregates in Alzheimer's Disease
Researchers here describe an interesting evolution of proteolysis targeting chimera (PROTAC) technology into a form that upregulates the dephosphorylation of tau protein. Tau becomes pathogenic in the aging brain when hyperphosphorylated, and thus reducing it back to its unphosphorylated form should provide benefits to patients in tauopathies such as Alzheimer's disease. The PROTAC style of approach, when applied to this situation, is to produce a molecule capable of binding to phosphorylated tau at one end and a phosphatase at the other. By encouraging phosphatase molecules into close proximity to phosphorylated tau, the ...
Source: Fight Aging! - April 4, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs