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home:diseases:aging [01.26.2019] – [Aging (senescence)] sallieqhome:diseases:aging [09.14.2022] (current) – external edit 127.0.0.1
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-The biological basis of aging (also known as senescence) is the subject of debate. A number of theories suggest aging is inevitable, the product of "wear and tear" or a result of some evolutionary necessity. For example, Skulachev argues that aging performs a specific biological function, with the turnover in new members of a species promoting greater evolutionary fitness.(({{pubmed>long:9467841}})) One of the longstanding problems of such theories is that they fail to account for dramatically different lifespans, or for the fact that chronic diseases are identical in presentation to diseases of the aging. We have a lot to learn about 'diseases of the aging'.+The biological basis of aging (also known as senescence) is the subject of debate. A number of theories suggest aging is inevitable, the product of "wear and tear" or a result of some evolutionary necessity. For example, Skulachev argues that aging performs a specific biological function, with the turnover in new members of a species promoting greater evolutionary fitness.(({{pmid>long:9467841}})) One of the longstanding problems of such theories is that they fail to account for dramatically different lifespans, or for the fact that chronic diseases are identical in presentation to diseases of the aging. We have a lot to learn about 'diseases of the aging'.
  
  [[https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-3-12/comments|Recovery from some of the diseases of aging]]  [[https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-3-12/comments|Recovery from some of the diseases of aging]]
  
-Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians.    (({{pubmed>long:26629551}})) +Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians.    (({{pmid>long:26629551}})) 
  
-Health of the hypothalamus may be a controlling factor as demonstrated in a mouse study by Yalin Zhang et al <blockquote> Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing.  [[http://www.nature.com/nature/journal/vaop/ncurrent/full/nature23282.html|Hypothalamic stem cells control ageing speed partly through exosomal miRNAs]]+Health of the hypothalamus may be a controlling factor as demonstrated in a mouse study by Yalin Zhang et al <blockquote> Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing.  [[https://www.nature.com/nature/journal/vaop/ncurrent/full/nature23282.html|Hypothalamic stem cells control ageing speed partly through exosomal miRNAs]]
 </blockquote>  </blockquote> 
  
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  Selectively ablating senescent cells using dasatinib plus quercetin (DQ) alleviates IPF-related dysfunction in bleomycin-administered mice.  Selectively ablating senescent cells using dasatinib plus quercetin (DQ) alleviates IPF-related dysfunction in bleomycin-administered mice.
  
-Our first-in-humans open-label pilot supports study feasibility and provides initial evidence that senolytics may alleviate physical dysfunction in IPF  (({{pubmed>long:30616998}})).</blockquote>+Our first-in-humans open-label pilot supports study feasibility and provides initial evidence that senolytics may alleviate physical dysfunction in IPF  (({{pmid>long:30616998}})).</blockquote>
 ===== Diseases of the aging are chronic diseases ===== ===== Diseases of the aging are chronic diseases =====
  
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 <blockquote>Aging is a super-category. We’ve gradually lumped together more and more symptoms under the category of natural aging. Many of these symptoms are the same as those caused by diseases that surely have an infectious cause. In that sense, you could view much of what we now call aging as an incapacitating illness that leads to a decrease in function. We know that inflammation and the interaction of the immune system with pathogens can destroy tissue. So it’s not surprising that the tissues of a person who harbors a lot of pathogens would age earlier and alter their biological structure earlier in life. I do believe it is inevitable that people will eventually die of old age, but I suspect that this should generally happen when they are 80-100 years old. But we are increasingly seeing signs of aging-related diseases in people who are much younger. <blockquote>Aging is a super-category. We’ve gradually lumped together more and more symptoms under the category of natural aging. Many of these symptoms are the same as those caused by diseases that surely have an infectious cause. In that sense, you could view much of what we now call aging as an incapacitating illness that leads to a decrease in function. We know that inflammation and the interaction of the immune system with pathogens can destroy tissue. So it’s not surprising that the tissues of a person who harbors a lot of pathogens would age earlier and alter their biological structure earlier in life. I do believe it is inevitable that people will eventually die of old age, but I suspect that this should generally happen when they are 80-100 years old. But we are increasingly seeing signs of aging-related diseases in people who are much younger.
  
-//**Paul Ewald**, [[http://bacteriality.com/2008/02/11/ewald/|Bacteriality interview]]//</blockquote>+//**Paul Ewald**, [[https://bacteriality.com/2008/02/11/ewald/|Bacteriality interview]]//</blockquote>
  
  
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 ===== Infection and decline in immune function ===== ===== Infection and decline in immune function =====
  
-A typical feature of aging is a chronic, low-grade inflammation characterized by a general increase in the production of pro-inflammatory cytokines and inflammatory markers.(({{pubmed>long:20388071}})) There is even a term for it: inflammaging. According to Franchesci: "A large part of the aging phenotype, including immunosenescence, is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status we proposed to call inflammaging."(({{pubmed>long:17116321}})) +A typical feature of aging is a chronic, low-grade inflammation characterized by a general increase in the production of pro-inflammatory cytokines and inflammatory markers.(({{pmid>long:20388071}})) There is even a term for it: inflammaging. According to Franchesci: "A large part of the aging phenotype, including immunosenescence, is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status we proposed to call inflammaging."(({{pmid>long:17116321}})) 
  
-Aging deeply affects (or is affected by!) the human microbiota's homeostasis with the host's immune system:(({{pubmed>long: 20498852}})) (({{pubmed>long:22283774}}))+Aging deeply affects (or is affected by!) the human microbiota's homeostasis with the host's immune system:(({{pmid>long: 20498852}})) (({{pmid>long:22283774}}))
  
-  * **autoimmune** – As people age, their risk for developing an "autoimmune" condition also increases.(({{pubmed>long:1822969}})) The article on [[home:alternate:autoimmunity|autoimmune conditions]] discusses why so-called “autoantibodies” are merely antibodies generated in response to pathogenic bacterial cells that have been destroyed as a result of an active immune response. +  * **autoimmune** – As people age, their risk for developing an "autoimmune" condition also increases.(({{pmid>long:1822969}})) The article on [[home:alternate:autoimmunity|autoimmune conditions]] discusses why so-called “autoantibodies” are merely antibodies generated in response to pathogenic bacterial cells that have been destroyed as a result of an active immune response. 
-  * **macrophage function** – Macrophages, which act as "pathogen sensors", lose the ability to initiate an inflammatory response as people age.(({{pubmed>long:15268749}})) Microbes use a variety of methods to infect macrophages. For example, //Neisseria meningitidis// prevents macrophage apoptosis via genes encoding nitric oxide detoxification and a porin, PorB.(({{pubmed>long:16369030}}))+  * **macrophage function** – Macrophages, which act as "pathogen sensors", lose the ability to initiate an inflammatory response as people age.(({{pmid>long:15268749}})) Microbes use a variety of methods to infect macrophages. For example, //Neisseria meningitidis// prevents macrophage apoptosis via genes encoding nitric oxide detoxification and a porin, PorB.(({{pmid>long:16369030}}))
  
  
-<blockquote>This theory is based on the fact that genes affecting host organism longevity are represented by subpopulations: genes of host eukaryotic cells, commensal microbiota, and non-living genetic elements. ........... we propose that lifespan and aging are defined by the accumulation of alterations over all genes of macroorganism and microbiome and the non-living genetic elements associated with them. (({{pubmed>long:29978435}}))  </blockquote>+<blockquote>This theory is based on the fact that genes affecting host organism longevity are represented by subpopulations: genes of host eukaryotic cells, commensal microbiota, and non-living genetic elements. ........... we propose that lifespan and aging are defined by the accumulation of alterations over all genes of macroorganism and microbiome and the non-living genetic elements associated with them. (({{pmid>long:29978435}}))  </blockquote>
  
  
 Could the chronic inflammation associated with aging be caused by pathogens? Given the crudeness of tools now used to measure microbes and the ubiquity of the human microbiota, this seems like a reasonable if not inevitable conclusion as the early studies have begun to suggest.  Could the chronic inflammation associated with aging be caused by pathogens? Given the crudeness of tools now used to measure microbes and the ubiquity of the human microbiota, this seems like a reasonable if not inevitable conclusion as the early studies have begun to suggest. 
  
-<blockquote>At present, a study on gut microbiota composition shows that three main modifications occur in faecal microbiota from old frail subjects: a 26-fold reduction in the number of lactobacilli (which stimulate immune functions and help the nutrient absorption), a 3-fold reduction in the number of bacteriodes (which digest polysaccarides, some species are opportunist pathogens) and a 7-fold increase in the number of enterobacteriacee (potentially pathogens)(({{pubmed>long:16204576}})). Differences in faecal microbiota were also found in a study on people of different countries and ages, including aged and long-lived people(({{pubmed>long:16461645}})).+<blockquote>At present, a study on gut microbiota composition shows that three main modifications occur in faecal microbiota from old frail subjects: a 26-fold reduction in the number of lactobacilli (which stimulate immune functions and help the nutrient absorption), a 3-fold reduction in the number of bacteriodes (which digest polysaccarides, some species are opportunist pathogens) and a 7-fold increase in the number of enterobacteriacee (potentially pathogens)(({{pmid>long:16204576}})). Differences in faecal microbiota were also found in a study on people of different countries and ages, including aged and long-lived people(({{pmid>long:16461645}})).
  
-//**E. Cevenini**//(({{pubmed>long:20388071}}))</blockquote>+//**E. Cevenini**//(({{pmid>long:20388071}}))</blockquote>
  
  
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 +===== Research into effects of Olmesartan =====
  
 +
 +[[home:food:aim_health:aging|Protective effects of Olmesartan]]
 ===== Role of vitamin D metabolism ===== ===== Role of vitamin D metabolism =====
  
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 <blockquote>Overall, VDR KO mice showed several aging related phenotypes, including poorer survival, early alopecia, thickened skin, enlarged sebaceous glands and development of epidermal cysts.... Unlike the wildtype controls, VDR KO mice lose their ability to swim after 6 months of age. Expression of all the genes was lower in old VDR KO mice, but only NF-kappaB, Fgf-23, p53 and IGF1R were significantly lower. Since the phenotype of aged VDR knockout mice is similar to mouse models with hypervitaminosis D(3), our study suggests that VDR genetic ablation promotes premature aging in mice, and that vitamin D(3) homeostasis regulates physiological aging. <blockquote>Overall, VDR KO mice showed several aging related phenotypes, including poorer survival, early alopecia, thickened skin, enlarged sebaceous glands and development of epidermal cysts.... Unlike the wildtype controls, VDR KO mice lose their ability to swim after 6 months of age. Expression of all the genes was lower in old VDR KO mice, but only NF-kappaB, Fgf-23, p53 and IGF1R were significantly lower. Since the phenotype of aged VDR knockout mice is similar to mouse models with hypervitaminosis D(3), our study suggests that VDR genetic ablation promotes premature aging in mice, and that vitamin D(3) homeostasis regulates physiological aging.
  
-//**T. Keisala** et al.//(({{pubmed>long:19500727}}))</blockquote>+//**T. Keisala** et al.//(({{pmid>long:19500727}}))</blockquote>
  
-  * **Vitamin D restriction reduces signs of aging in certain mice** – The Klotho-insufficient (klotho) mouse exhibits a syndrome that resembles human aging including retarded growth, osteoporosis, atherosclerosis, ectopic calcification, immunological deficiency, skin and general organ atrophy, hypogonadism and short lifespan.(({{pubmed>long:19444937}})) This syndrome is mitigated – in one researcher's words, "rescued" – when mice have their vitamin D restricted.(({{pubmed>long:21276773}})) Interestingly, while murine research is a mainstay of the community of researchers and patients interested in longevity, this line of research has not led for calls to restrict vitamin D in the name of health.+  * **Vitamin D restriction reduces signs of aging in certain mice** – The Klotho-insufficient (klotho) mouse exhibits a syndrome that resembles human aging including retarded growth, osteoporosis, atherosclerosis, ectopic calcification, immunological deficiency, skin and general organ atrophy, hypogonadism and short lifespan.(({{pmid>long:19444937}})) This syndrome is mitigated – in one researcher's words, "rescued" – when mice have their vitamin D restricted.(({{pmid>long:21276773}})) Interestingly, while murine research is a mainstay of the community of researchers and patients interested in longevity, this line of research has not led for calls to restrict vitamin D in the name of health.
  
 ===== Falls and Fractures ===== ===== Falls and Fractures =====
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 On their way to the cell’s surface, phospholipids more easily attach themselves to CD1d molecules, making it more difficult for glycolipids to attach to CD1d. Because of this, it is harder for glycolipids to make it to the surface of the cell. This means that iNKTs cannot be as easily stimulated by glycolipids. On their way to the cell’s surface, phospholipids more easily attach themselves to CD1d molecules, making it more difficult for glycolipids to attach to CD1d. Because of this, it is harder for glycolipids to make it to the surface of the cell. This means that iNKTs cannot be as easily stimulated by glycolipids.
  
-Scientists believe iNKT cells are necessary because they appear to protect cells against the progression of certain cancers and autoimmune diseases. However, iNKT cells are extremely active and can cause alcoholic hepatitis or other types of liver diseases if they are overstimulated. The phospholipid’s ability to more easily bind to CD1d molecules than glycolipids keeps a balance between the two cell types and maintains homeostasis in the immune system.   (({{pubmed>long:30508304}})) +Scientists believe iNKT cells are necessary because they appear to protect cells against the progression of certain cancers and autoimmune diseases. However, iNKT cells are extremely active and can cause alcoholic hepatitis or other types of liver diseases if they are overstimulated. The phospholipid’s ability to more easily bind to CD1d molecules than glycolipids keeps a balance between the two cell types and maintains homeostasis in the immune system.   (({{pmid>long:30508304}})) 
 ===== Read more ===== ===== Read more =====
  
-  * **Declining testosterone levels in men not part of normal aging, study finds** – A [[http://www.eurekalert.org/pub_releases/2012-06/tes-dtl062212.php|2012 study]] found that declining testosterone levels are not an inevitable part of the aging process, as many people think. Men who had declines in testosterone were more likely to be those who became obese, had stopped smoking or were depressed at either clinic visit.+  * **Declining testosterone levels in men not part of normal aging, study finds** – A [[https://www.eurekalert.org/pub_releases/2012-06/tes-dtl062212.php|2012 study]] found that declining testosterone levels are not an inevitable part of the aging process, as many people think. Men who had declines in testosterone were more likely to be those who became obese, had stopped smoking or were depressed at either clinic visit.
   * [[https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-3-12/comments|We have a lot to learn about 'diseases of the aging']]   * [[https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-3-12/comments|We have a lot to learn about 'diseases of the aging']]
  
- 
-==== summary of research into effects of Olmesartan ==== 
- 
- 
-[[home:food:aim_health:aging|Protective effects of Olmesartan]] 
- 
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 {{tag>diseases}} {{tag>diseases}}
 +<nodisp>
 ===== Notes and comments ===== ===== Notes and comments =====
    
 //Lee// " I am 70 now (not 65) when we started this conversation ...lolDr's were amazed that I was in such good shape and all fractures were closed and healed well. I would like to say I may not bicycle ride now ..but it's a family thing and I probably will " //Lee// " I am 70 now (not 65) when we started this conversation ...lolDr's were amazed that I was in such good shape and all fractures were closed and healed well. I would like to say I may not bicycle ride now ..but it's a family thing and I probably will "
  
-  (({{pubmed>long:000}})) +  (({{pmid>long:000}})) 
      
 <DiseaseHierarchy> <DiseaseHierarchy>
  
-  * [[http://www.marshallprotocol.com/forum37/10103.html]] s259 +  * [[https://www.marshallprotocol.com/forum37/10103.html]] s259 
-  * [[http://www.marshallprotocol.com/view_topic.php?id=9759&forum_id=37&jump_to=126260#p126260]] s263+  * [[https://www.marshallprotocol.com/view_topic.php?id=9759&forum_id=37&jump_to=126260#p126260]] s263
  
  
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 <blockquote> As far as I can see, Th1 pathogens start to dictate the 'health' of just about everyone as they age. If you draw a graph of 25-D levels vs age, they drop steadily after age 40. Something is happening, even during 'healthy aging', that we really ought to understand a little more :) <blockquote> As far as I can see, Th1 pathogens start to dictate the 'health' of just about everyone as they age. If you draw a graph of 25-D levels vs age, they drop steadily after age 40. Something is happening, even during 'healthy aging', that we really ought to understand a little more :)
  
-There is a branch of medicine which is starting to look at Immunity and Aging. Here is a short letter I recently wrote to the editor of one of the journals: [[http://www.immunityageing.com/content/3/1/12/comments]]+There is a branch of medicine which is starting to look at Immunity and Aging. Here is a short letter I recently wrote to the editor of one of the journals: [[https://www.immunityageing.com/content/3/1/12/comments]]
  
 //**Trevor Marshall, PhD**// </blockquote> //**Trevor Marshall, PhD**// </blockquote>
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 {{ :home:pathogenesis:cawthon3.gif|Association of telomere length with mortality}} {{ :home:pathogenesis:cawthon3.gif|Association of telomere length with mortality}}
  
-Cawthorn et al examined the [[http://en.wikipedia.org/wiki/Telomere|telomeres]] of 143 people over the age of 60.(({{pubmed>long:12573379}})) Telomeres are DNA sequences on the ends of chromosomes that are gradually lost as cells replicate. The team found that those with shorter telomeres in blood DNA had significantly poorer survival, attributable in part to a 3.18-fold higher mortality rate from heart disease and, tellingly, a 8.54-fold higher mortality rate from infectious disease. +Cawthorn et al examined the [[https://en.wikipedia.org/wiki/Telomere|telomeres]] of 143 people over the age of 60.(({{pmid>long:12573379}})) Telomeres are DNA sequences on the ends of chromosomes that are gradually lost as cells replicate. The team found that those with shorter telomeres in blood DNA had significantly poorer survival, attributable in part to a 3.18-fold higher mortality rate from heart disease and, tellingly, a 8.54-fold higher mortality rate from infectious disease. 
  
 A number of the sickest patients on the Marshall Protocol, who are killing intracellular bacteria at the fastest rate possible, take over three years to completely recover their health. This hints at the large amount of pathogen-altered DNA that many people, even those who are not yet displaying the hallmarks of Th1 disease, are carrying. A number of the sickest patients on the Marshall Protocol, who are killing intracellular bacteria at the fastest rate possible, take over three years to completely recover their health. This hints at the large amount of pathogen-altered DNA that many people, even those who are not yet displaying the hallmarks of Th1 disease, are carrying.
  
  
-Study shows that most older adults have signs of brain damage [[http://bacteriality.com/2008/01/04/brain/]]+Study shows that most older adults have signs of brain damage [[https://bacteriality.com/2008/01/04/brain/]]
  
  
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 People who haven’t completed the MP consider it inevitable that as they age, they will need to stock up on any number of medications including thyroid medications, cardiac meds, statins, NSAIDS, B/P meds, etc. But people who have reached the later stages of the MP see no reason why they cannot take their level of healing to a maximum – to a point where they will never need these medications and may experience great health during their elder years. People who haven’t completed the MP consider it inevitable that as they age, they will need to stock up on any number of medications including thyroid medications, cardiac meds, statins, NSAIDS, B/P meds, etc. But people who have reached the later stages of the MP see no reason why they cannot take their level of healing to a maximum – to a point where they will never need these medications and may experience great health during their elder years.
  
-//**Amy Proal**, [[http://bacteriality.com/2008/02/23/misconceptions/#13|Top 14 misconceptions about the MP: addressed and explained]]//</blockquote>+//**Amy Proal**, [[https://bacteriality.com/2008/02/23/misconceptions/#13|Top 14 misconceptions about the MP: addressed and explained]]//</blockquote>
  
  
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-<blockquote>Hypothesis: The Aging Paradox and Autoimmune Disease(({{pubmed>long:1822969}}))+<blockquote>Hypothesis: The Aging Paradox and Autoimmune Disease(({{pmid>long:1822969}}))
 Authors: Eyal Talora; Noel R. Rosea Authors: Eyal Talora; Noel R. Rosea
  
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 the cells is good, bad or indifferent. the cells is good, bad or indifferent.
  
-http://www.nytimes.com/2011/11/03/science/senescent-cells-hasten-aging-but-can-be-purged-mouse-study-suggests.html+https://www.nytimes.com/2011/11/03/science/senescent-cells-hasten-aging-but-can-be-purged-mouse-study-suggests.html
 </blockquote> </blockquote>
-===== References =====+===== References =====</nodisp> 
home/diseases/aging.1548468332.txt.gz · Last modified: 01.26.2019 by sallieq
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