The Infection-Senescence Hypothesis of Alzheimer’s Disease

With the continued failure of clinical trials of therapies for Alzheimer’s disease, largely immunotherapies, that aim to clear amyloid-β, a growing faction of researchers are rejecting the amyloid hypothesis. In that mainstream view of the condition, the accumulation of amyloid-β causes the early stages of Alzheimer’s, but in addition to disrupting the function of neurons, it also causes immune cells in the brain to become inflammatory, dysfunctional, and senescent. This in turn sets the stage for the aggregation of tau protein into neurofibrillary tangles, which causes widespread cell death and the much more severe manifestations of later stage Alzheimer’s disease. Why do only some old people exhibit the condition? In the mainstream view, this is equivalent to asking why only some old people have significantly […]

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Fibrates as a Potential Class of Senolytic Therapy to Clear Senescent Cells

Accumulation of senescent cells with age is one of the causes of aging. In recent years, the broader scientific community has become convinced of this point, and thus funding is now directed towards many varied investigations of cellular senescence and what to do about it. A young industry has emerged, made up of biotech companies focused on the selective destruction of senescent cells, mostly using small molecule drugs. Since these drugs operate through different mechanisms, tend to be tissue specific, only clear a fraction of senescent cells that varies by tissue, and will thus probably be more effective when combined together, research continues to find ever more senolytic compounds. Senescent cells are created constantly, either in response to damage or a toxic local environment, or […]

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Gene Therapy in Mice Alters the Balance of Macrophage Phenotypes to Slow Atherosclerosis Progression

Atherosclerosis causes a sizable fraction of all deaths in our species. It is the generation of fatty deposits in blood vessel walls, distorting, narrowing, and weakening the blood vessels. This ultimately leads to the major structural failure of a stroke or heart attack, in which a vital blood vessel ruptures or is blocked. Lipids, such as cholesterols, are carried in the blood stream throughout life, associated with low-density lipoprotein (LDL) particles. The innate immune cells known as macrophages are responsible for removing cholesterol from blood vessel walls via the processes of reverse cholesterol transport: macrophages ingest the cholesterol and pass it on to high-density lipoprotein (HDL) particles, which carry it back to the liver for excretion. In youth, reverse cholesterol transport keeps blood vessels in […]

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MitoCeption as a Method of Artificial Mitochondrial Transfer

Mitochondria are the power plants of the cell, hundreds of bacteria-like organelles that divide like bacteria and are selectively destroyed when damaged by cellular quality control mechanisms. They carry out the energetic chemical reactions needed to package the chemical energy store molecule ATP that is used to power cellular processes. Some of the protein machinery vital to this function is encoded in mitochondrial DNA, a circular genome that resides in mitochondria themselves rather than in the cell nucleus with the majority of a cell’s DNA. It is this DNA that is the Achilles’ heel of mitochondria, as it is less well protected and repaired than is the case for nuclear DNA. It becomes damaged over time, and this damage leads to dysfunction in mitochondria and […]

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The Question of a Limit to Human Life Span

There has been much discussion in the aging research community these past few years on the topic of whether or not there is a limit to human life span, and how one might even go about defining such a thing. While life spans are in a slow upward trend due to general improvements in medical technology, can this trend continue without end, or will it run into a roadblock? In essence this is a debate over what can be extracted from poor data, and which data is in fact poor. Since there are few extremely old people, and since verifying age becomes ever harder the further back one has to go to search for records, the data for human mortality at advanced ages is very […]

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Telomere Dynamics with Age are Very Different Between Mammalian Species

Telomeres are caps of repeated DNA sequences at the ends of chromosomes. They shorten with each cell division, a part of the mechanism that ensures somatic cells can only replicate a limited number of times. Telomerase acts to lengthen telomeres, and in humans telomerase is only active in stem cells. Thus our cells exist in a two-tier system, in which only tiny populations of privileged stem cells are permitted unrestricted replication, while the vast majority of somatic cells are limited. Matters are similar across all higher animals, and this state of affairs likely evolved because it keeps cancer to a low enough level, and pushed off far enough into late life, for allow for evolutionary success. A lot of ink has been spilled on the […]

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Both Extracellular Vesicles and Secreted Proteins can Spread Cellular Senescence

The accumulation of senescent cells with age is one of the root causes of aging. Senescent cells never amount to more than a few percent of all cells, even in late life, but they secrete a mix of extracellular vesicles and various proteins that is inflammatory and disruptive to tissue function. This is known as the senescence-associated secretory phenotype, or SASP. Since senescent cells inflect harm through signaling, it doesn’t take many such cells to act as a contributing cause of age-related disease and organ dysfunction. The research community is nowadays fully invested in the concept that senescent cells are a meaningful cause of aging. This is a comparatively recent development, despite the fact that the evidence was sizable and evident for several decades. It […]

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More Supporting Evidence for Pancreatic Fat to be the Cause of Type 2 Diabetes

Type 2 diabetes is, for the vast majority of patients, a condition caused by being significantly overweight. Age does has an influence on the risk of being overweight leading to metabolic syndrome and then type 2 diabetes; it is reasonable to say that type 2 diabetes is an age-related condition. In essence, the younger you are, the more fat tissue it requires to push your metabolism over the red line. A few years back, researchers demonstrated that it is specifically fat in the pancreas that causes type 2 diabetes. Of course the only way to put that fat into the pancreas in the normal course of affairs is to become very overweight, creating fat tissue around all of the organs important to metabolism, and negatively […]

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Rate of Telomere Shortening Correlates with Species Average Life Span

Researchers here report on data showing a correlation between species life span and pace of telomere shortening. Telomeres are the repeated DNA sequences at the ends of chromosomes. A little is lost with each cell division, during replication of DNA, and cells with very short telomeres become senescent or self-destruct. This is how the vast majority of cells in the body are limited in their replicative capacity, in order to lower the risk of damaged cells becoming cancerous to an evolutionarily acceptable level. Not a personally acceptable level, of course. With age, average telomere length tends to shorten in most species, and this is most likely a reflection of loss of stem cell function. Stem cells maintain long telomeres via use of telomerase, and thus […]

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LANDO Found to be Key to Microglial Clearance of Amyloid-β and Neuroinflammation

The consensus view on the progression of Alzheimer’s disease is that it begins with rising levels of amyloid-β aggregates, misfolded proteins forming solid deposits to disrupt cellular behavior. This increase in amyloid-β might be due to persistent infection, as amyloid-β is an antimicrobial peptide, a part of the innate immune system. It might be due to failing drainage of cerebrospinal fluid, causing all molecular wastes to build up in the brain. There are other possibilities as well, such as progressive failure of the ability of immune cells to clear out amyloid-β. In and of itself this rising level of amyloid-β seems to, at worst, cause mild cognitive impairment via dysfunction of neurons. Unfortunately it also causes microglia and other support cells to become dysfunctional and […]

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