Fight Aging! Newsletter, April 1st 2024
This study supports the proposed model that aging-related loss of colonic crypt epithelial cell AMP gene expression can promote increased relative abundances of Gn inflammaging-associated bacteria and gene expression markers of colonic inflammaging. These data may support new targets for aging-related therapies based on intestinal genes and microbiomes.
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A Skeptical View of the Role of Nuclear DNA Damage in Aging
https://www.fightaging.org/archives/2024/03/a-skeptical-view-of-the-role-of-nuclear-dna-damage-in-aging/
It is evident and settled that stochastic nuclear DNA damag...
Source: Fight Aging! - March 31, 2024 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs
Problematic B Cells Accumulate in Visceral Fat and Indirectly Provoke Inflammation
The authors of today's open access paper present an interesting and novel way in which visceral fat tissue provokes chronic inflammation. It has been noted that dysfunctional B cells accumulate with age. Here, dysfunctional B cells of a specific subtype are shown to accumulate in aged visceral fat tissue, acting to provoke other immune cells in visceral fat tissue, such as macrophages, into a more pro-inflammatory state. The researchers demonstrate that removing the B cell population helps to reduce the age-related inflammation generated by visceral fat by removing the contribution to inflammatory macrophage behavior.
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Source: Fight Aging! - March 29, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Tristetraprolin Upregulation Reduces Frailty and Increases Bone Density in Old Mice
Researchers here report that life-long tristetraprolin (TTP) upregulation leads to reduced frailty and improved bone mineral density in aged mice. One of the functions of TTP is that it suppresses expression of the pro-inflammatory TNF-α cytokine, so a reduced degree of age-related inflammation would be the first place to look for an explanation of the outcome noted here. It is an open question as to whether TTP upregulation produces a more nuanced and reactive reduction of TNF-α signaling than is the case for the blunt, across the board inhibition achieved by present anti-TNF-α therapies, and is thus a mechanism that i...
Source: Fight Aging! - March 29, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Regulatory T Cells Contribute to Reduced Myelination in the Aging Brain
Myelin surrounds the axons that connect neurons to one another, and is required for the transmission of electrical impulses. This myelin sheath is maintained by oligodendrocytes. These cells do not carry out their work in isolation; a great many factors are involved in determining the size and capabilities of the oligodendrocyte population. Aging is disruptive to the myelination carried out by oligodendrocytes. The consequences are not as bad as the profound loss of myelin that takes place in demyelinating diseases such as multiple sclerosis, but age-related loss of myelination does appear to degrade cognitive function. Re...
Source: Fight Aging! - March 29, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
A Skeptical View of the Role of Nuclear DNA Damage in Aging
It is evident and settled that stochastic nuclear DNA damage contributes to cancer. The more of it that you have, the worse your risk. What is still very much debated is whether nuclear DNA damage contributes meaningfully to degenerative aging, and how it does so. Most mutational damage to DNA occurs in regions that are inactive, in cells that have comparatively few divisions remaining before reaching the Hayflick limit. Even if damage alters the function of such a cell, in some non-cancerous way, it is unclear as to how this could amount to a meaningful contribution to loss of tissue function.
The one school of tho...
Source: Fight Aging! - March 28, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Further Considering the Altered Transcription of Longer Genes with Age
The machinery of gene expression changes with age. In recent years, it has been noted that the length of gene sequences correlates with the degree to which transcription of gene sequences into RNA molecules changes over the course of aging. Later work has started to examine the proximate causes of these changes, various fine detail mechanisms buried in the depths of transcription. The research community is not yet at the point of being able to conclusively demonstrate that altered transcription of longer genes produces meaningful downstream consequences in degenerative aging, as interventions specifically targeting just th...
Source: Fight Aging! - March 28, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Inhibiting P16 in Microglia Reduces Amyloid Plaques in Mice
Researchers here show that targeting microglia in a mouse model of Alzheimer's disease to suppress p16 expression can reduce amyloid-β plaques. This appears to be a way to interfere in a maladaptive reaction to amyloid-β on the part of microglia, innate immune cells responsible for clearing molecular debris from brain tissue. P16 is a marker of cellular senescence, though may also be characteristic of non-senescent but still problematic, pro-inflammatory microglia. There is a good amount of evidence to suggest that both senescent and overly active microglia are important to the progression of neurodegenerative conditions...
Source: Fight Aging! - March 28, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Loss of Anti-Microbial Peptides as a Mechanism for Age-Related Changes in Gut Microbiome Composition
This study supports the proposed model that aging-related loss of colonic crypt epithelial cell AMP gene expression promotes increased relative abundances of Gn inflammaging-associated bacteria and gene expression markers of colonic inflammaging. These data may support new targets for aging-related therapies based on intestinal genes and microbiomes. (Source: Fight Aging!)
Source: Fight Aging! - March 27, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Lipid Droplets in Microglia Involved in Alzheimer's Pathology
Microglia are innate immune cells resident in the central nervous system. Microglial dysfunction is clearly a contributing factor in the onset and progression of age-related neurodegenerative conditions, including Alzheimer's disease, as well as the accompanying chronic inflammation of brain tissue. As to why microglia become problematic and inflammatory, there are any number of possible contributing mechanisms to consider. Cellular senescence, mitochondrial dysfunction, reactions to cell debris or the presence of persistent viral infections, and more. In this vein, researchers here discuss excessive lipid accumulation in ...
Source: Fight Aging! - March 27, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
More Commentary on the Role of PF4 in Reducing Brain Inflammation
Platelets in the blood are not just involved in clotting. Near every aspect of our biology has evolved many different functions, and the complexity of our biochemistry is still far from fully explored. Increased platelet factor 4 (PF4) shows up as a feature in a number of different interventions known to reduce inflammation in the aging brain. Researchers are now moving in the direction of developing therapies for neurodegenerative conditions based on the upregulation of PF4 or the delivery of recombinant PF4.
Platelets are a component of blood best known for their role in clotting, but research in recent years ha...
Source: Fight Aging! - March 27, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Interesting Epidemiological Results for Time Restricted Feeding
In this study, researchers investigated the potential long-term health impact of following an 8-hour time-restricted eating plan. They reviewed information about dietary patterns for participants in the annual 2003-2018 National Health and Nutrition Examination Surveys (NHANES) in comparison to data about people who died in the U.S., from 2003 through December 2019, from the Centers for Disease Control and Prevention's National Death Index database.
The analysis found: (a) people who followed a pattern of eating all of their food across less than 8 hours per day had a 91% higher risk of death due to cardiovascular d...
Source: Fight Aging! - March 26, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Apigenin, Sleep, and Aging
For those following research into efforts to upregulate NAD+ levels to improve mitochondrial function, this paper is an interesting sidebar. Some degree of loss of NAD+ emerges from increased activity of CD38. Apigenin is a dietary supplement that can modestly influence both sleep and pace of aging, the latter in short-lived laboratory species at least. Apigenin can increase NAD+ levels by inhibiting CD38 activity. Like much of metabolism, this is all very interesting, but the effect sizes are nothing to write home about. If upregulating NAD+ levels is the goal, you'll do better by exercising. The fundamental flaw in so mu...
Source: Fight Aging! - March 26, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
MKK4 Inhibition Provokes Greater Liver Regeneration
Researchers here report on an approach to meaningfully stimulate the regenerative capacity of the liver. The liver is one of the few organs capable of significant regrowth in mammals, and the way in which it does so is quite different from the regenerative response found in other tissues. Thus while the results here are quite impressive, they don't apply to other organs. This is purely a way to manipulate the regulation of liver regeneration.
One key feature of acute and chronic liver diseases, and after extended liver resections, is the inability of hepatocytes to sufficiently regenerate and restore or maintain a...
Source: Fight Aging! - March 26, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Predicting the Order of Arrival of the First Rejuvenation Therapies
It has been going on eight years since I last speculated on the order of arrival of the first rejuvenation therapies. Tempus fugit, and time for an updated version! Eight years is a long enough span of time for the first of those rejuvenation therapies to now exist, albeit in a prototypical form, arguably proven in principle but not concretely. The world progresses but my biases remain much the same: the first rejuvenation therapies to work well enough to merit the name will be based on the SENS vision, that aging is at root caused by a few classes of accumulated cell and tissue damage, and biotechnologies that either repa...
Source: Fight Aging! - March 25, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Thoughts on Micronutrient Intake During Calorie Restriction
Despite the considerable attention given to calorie restriction and intermittent fasting in the research community, there is very little formalism applied to the practice in humans. The few clinical trials conducted to date have had to pick their own protocols, and it is only comparatively recently that the fasting mimicking diet was developed to plant a flag on one specific implementation. The challenge here is that it is difficult to monetize calorie restriction and fasting, and thus there is no push towards standardization or more detailed assessment of variant protocols from any of the usual parties who might otherwise...
Source: Fight Aging! - March 25, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
