A View of Recent Thought on the Amyloid Cascade Hypothesis of Alzheimer's Disease
Biochemistry is complex, and particularly so in the brain. The amyloid cascade hypothesis of Alzheimer's disease essentially states that slow aggregation of amyloid-β over years causes the onset of later and much more severe stages of Alzheimer's disease, meaning the chronic inflammation in brain tissue and tau aggregation that kills neurons. The hypothesis has so far survived the failure of amyloid-β clearance via immunotherapy to produce patient benefits, as well as the evidence for a subset of older individuals to exhibit high levels of amyloid-β without progressing to Alzheimer's disease. Researchers continue to exp...
Source: Fight Aging! - September 13, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Fight Aging! Newsletter, September 13th 2021
In this study, mature DCs (mDCs), generated from the GM-CSF and IL-4 induced bone marrow cells, were intravenously injected into wild-type mice. Three days later, assays showed that the mDCs were indeed able to return to the thymus. Homing DCs have been mainly reported to deplete thymocytes and induce tolerance. However, medullary TECs (mTECs) play a crucial role in inducing immune tolerance. Thus, we evaluated whether the mDCs homing into the thymus led to TECs depletion. We cocultured mDCs with mTEC1 cells and found that the mDCs induced the apoptosis and inhibited the proliferation of mTEC1 cells. These effects were onl...
Source: Fight Aging! - September 12, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

The Evolutionary Layering of the Mechanisms of Aging
Aging is the accumulation of molecular damage and the consequences of that damage. This molecular damage and its immediate consequences are comparatively simple to describe, but the damage takes place in a fantastically complex system of cells, cellular interactions, tissues, organs, organ interactions, and more. Every problem causes cascading, interacting chains of cause and effect, hard to pick apart via inspection and hard to reason about. Cellular metabolism and tissue structure and function are far from fully mapped, and aging involves sweeping changes throughout the organism and its countless subsystems. Today...
Source: Fight Aging! - September 9, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

A Study of Nattokinase Supplementation Shows No Effect on Progression of Atherosclerosis
You might recall a Chinese study from a few years back claiming a sizable effect on atherosclerotic plaque for supplementation with nattokinase. The result was a 36% reversal in plaque size, which is several times larger than can be reliably achieved with approaches such as statins and their successors, drugs that lower blood cholesterol. The dose was 6000FU/day for 6 months. My attention was recently drawn to the publication of results for a US study using dose of 2000FU/day for several years. In that study, there was no effect on the progression of atherosclerosis, and certainly no marked reversal. Medicine in gen...
Source: Fight Aging! - September 8, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Fight Aging! Newsletter, August 30th 2021
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out mo...
Source: Fight Aging! - August 29, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Osteopontin in Blood Samples as a Biomarker of Aging
Much of this paper is taken up with a consideration of osteopontin in macular degeneration, but the authors also note that ostopontin levels in blood plasma are higher in older individuals. This may be connected to increased production in the vasculature, associated with rising levels of chronic inflammation in later life. Past work has also shown that osteopontin levels decline in bone marrow tissue with age, and that this is connected to the dysfunction of the hematopoietic system responsible for generating immune cells. Nothing is simple in the biochemistry of aging. A common clinical phenotype of several neuro...
Source: Fight Aging! - August 26, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, August 23rd 2021
In this study, we used the UK Biobank (n = 440,185) to resolve previous ambiguities in the relationship between serum IGF-1 levels and clinical disease. We examined prospective associations of serum IGF-1 with mortality, dementia, vascular disease, diabetes, osteoporosis, and cancer, finding two generalized patterns. First, IGF-1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy; younger individuals with high IGF-1 are protected from disease, while older individuals with high IGF-1 are at increased risk for incident disease or death. Second, the association between IGF-1 and risk ...
Source: Fight Aging! - August 22, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

The Antagonistic Pleiotropy of IGF-1 Signaling in Aging
In this study, we used the UK Biobank (n = 440,185) to resolve previous ambiguities in the relationship between serum IGF-1 levels and clinical disease. We examined prospective associations of serum IGF-1 with mortality, dementia, vascular disease, diabetes, osteoporosis, and cancer, finding two generalized patterns. First, IGF-1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy; younger individuals with high IGF-1 are protected from disease, while older individuals with high IGF-1 are at increased risk for incident disease or death. Second, the association between IGF-1 and risk ...
Source: Fight Aging! - August 18, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Continued Discussion of the Ability of Immunotherapies to Remove Amyloid- β from the Brain
Is amyloid-β aggregation an important cause of Alzheimer's disease, or is it a side-effect of other, more important mechanisms? Near all age-related conditions are complex, with multiple interacting mechanisms involved. Absent a way to remove just one of those mechanisms, it is quite hard to say which are more or less important. In Alzheimer's disease this is made worse by the fact that the animal models are very artificial: few shorter lived mammals naturally develop anything even remotely resembling the biochemistry of Alzheimer's disease. Thus whether or not a treatment produces benefits in animal models is a poor indi...
Source: Fight Aging! - August 16, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Fight Aging! Newsletter, August 16th 2021
In conclusion, cancer survivors, especially older individuals, demonstrate greater odds of and accelerated functional decline, suggesting that cancer and/or its treatment may alter aging trajectories. Linking Particulate Air Pollution and Dementia in a Small Region of the US https://www.fightaging.org/archives/2021/08/linking-particulate-air-pollution-and-dementia-in-a-small-region-of-the-us/ It is fairly settled that evident particulate air pollution, such as daily exposure to smoke from wood-fueled cooking fires, has a strongly detrimental effect on long-term health. The mechanisms involved are inflam...
Source: Fight Aging! - August 15, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Biology Beyond the Lab: Using Computers to Study Life
Learn more about Dr. Melissa Wilson’s computational biology research in another Biomedical Beat blog post. Credit: Jacob Sahertian, ASU. “You’re not going to be able to do biology without understanding programming in the future,” Melissa Wilson, Ph.D., an associate professor of genomics, evolution, and bioinformatics at Arizona State University, said in her 2019 NIGMS Early Career Investigator Lecture. “You don’t have to be an expert programmer. But without understanding programming, I can assert you won’t be able to do biology in the next 20 years.” A growing number of researchers, like Dr. Wils...
Source: Biomedical Beat Blog - National Institute of General Medical Sciences - August 11, 2021 Category: Research Authors: Chrissa Chverchko Tags: Being a Scientist Tools and Techniques Bioinformatics Computational Biology Cool Tools/Techniques Profiles Source Type: blogs

Linking TDP-43 Dysfunction, Cholesterol, and Maintenance of Myelin in Neurodegeneration
TDP-43 is one of the few proteins in the body that can misfold in ways that lead to solid aggregates that disrupt cell and tissue function. The biochemistry and relevance of TDP-43 is a more recent area of research in comparison to the study of, say, amyloid-β in Alzheimer's disease and α-synuclein in Parkinson's disease, but it appears important to the progression of a number of neurodegenerative conditions. Researchers here elaborate on the relationship between TDP-43 and age-related demyelination, the corrosion of myelin sheathing around axons that is necessary for nervous system function, normally maintained by a pop...
Source: Fight Aging! - August 11, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

VEGF Upregulation Slows Age-Related Capillary Density Loss, Extending Health and Life Span in Mice
The aging of the vasculature has detrimental effects on organs throughout the body. The most structurally apparent issue is that of atherosclerosis, the buildup of fatty deposits that narrow and weaken blood vessels. This ultimately leads to heart failure, stroke, heart attack, and death. A close second is the stiffening of blood vessels, due to a variety of processes such as cross-linking to reduce elasticity in blood vessel walls, and inflammation-linked disruption of the vascular smooth muscle tissue responsible for contraction and dilation of blood vessels. This stiffening causes raised blood pressure, which in turn pr...
Source: Fight Aging! - August 10, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Fight Aging! Newsletter, August 9th 2021
In conclusion, the present study supports that some age-related diseases as well as education are causally related to longevity and highlights several new targets for achieving longevity, including management of venous thromboembolism, appropriate intake of sugar, and control of body fat. Our results warrant further studies to elucidate the underlying mechanisms of these reported causal associations. Pol III Inhibition Extends Longevity in Short-Lived Species https://www.fightaging.org/archives/2021/08/pol-iii-inhibition-extends-longevity-in-short-lived-species/ As this paper notes, Pol III is downstrea...
Source: Fight Aging! - August 8, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

On the Mechanisms of Late-Life Depression
Major depressive disorder, more commonly known as depression, is all too prevalent a part of the human condition. Like many aspects of brain function, a great many layered mechanisms are investigated and debated by the research community, while still being poorly understood as a whole. Pharmaceutical treatments for depression are actually quite good for those people that they work for, but finding the right treatment can be a haphazard, experimental journey of years and different approaches for those who suffer. We might suspect that these treatments are essentially compensatory in nature, touching on mechanisms (such as s...
Source: Fight Aging! - August 5, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs