Isomerization of Tau May be Involved in Alzheimer's Disease

Why do only some people develop Alzheimer's disease? Why do only some people with evidence of amyloid and tau protein aggregation in brain tissue also exhibit dementia? These are important questions. Researchers here provide evidence to suggest that whether or not tau protein is isomerized is relevant to the onset and progression of Alzheimer's disease. Isomers of the same molecule have the same molecular weight but a different structure and chemistry. Whether or not isomers of important proteins are present in significant numbers is not well studied in the context of neurodegenerative conditions; perhaps it should be. The researchers here suggest that reduced protein quality control due to faltering autophagy may be to blame for increased isomerization; where this fits into the bigger picture of Alzheimer's pathology is an open question. Recent work has posited a connection between Alzheimer's disease (AD) and isomerization of amino acids in long-lived proteins, which may interfere with lysosomal digestion. Herein, we reanalyzed data originally recorded for global proteomic analysis to look for isomerized peptides, which occur as a result of spontaneous chemical modifications to long-lived proteins. Examination of a large set of human brain samples revealed a striking relationship between Alzheimer's disease (AD) status and isomerization of aspartic acid in a peptide from tau. Relative to controls, a surprising increase in isomer abundance was found in both AD sampl...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs

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In this study, we showed that the iPaD (inducing Plagl2 and anti-Dyrk1a) lentivirus substantially rejuvenated the proliferative and neurogenic potential of NSCs in the aged brain. Clonal analysis by a sparse labeling approach as well as transcriptome analysis indicated that iPaD can rejuvenate aged NSCs (19-21 mo of age) to a level comparable with those at 1 or 2 months of age and successfully improved cognition of aged mice. Once rejuvenated and activated by iPaD, aged dormant NSCs can generate, on average, 4.9 neurons but very few astrocytes in 3-week tracing. Furthermore, these activated NSCs were maintained for ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Well, here we are again, at the end of another pandemic year, a year older and - hopefully - a year wiser and more knowledgeable. I said all that really needs to be said on the topic of COVID-19 as an age-related condition at the end of last year. We might hope that, given widespread vaccination, the pandemic will become a topic of diminishing importance as the year ahead progresses, even given the present round of variants, fears, and reintroduction of restrictions. Advocacy for Aging Research Have we finally made significant progress in convincing the world that aging is the cause of age-related disease, th...
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In conclusion, the low dose, prolonged angiotensin II exposure is associated with the induction of senescence in kidneys and the promotion of an inflammatory microenvironment through both secreted factors and immune cells. Endothelial cells appear to be a major cell type impacted. The elimination of senescent cells in the INK-ATTAC transgenic model prevents these effects of angiotensin II and reveals a novel pathophysiologic mechanism amenable to targeting by senolytic drugs in development. CYTOR Upregulation as a Path to Improved Muscle Function in Later Life https://www.fightaging.org/archives/2021/12/cytor-u...
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In conclusion, there is a good amount of pre-clinical and clinical data showing a strong positive correlation between reduction of senescent cells frequencies and functional improvement of skin. Whether senescence of skin cells makes a significant causal contribution to skin ageing can still not be conclusively decided, however. Nonetheless, there is strong evidence existing today to assume that better understanding of cell senescence in skin may lead to a breakthrough in interventions into skin ageing. Isomerization of Tau May be Involved in Alzheimer's Disease https://www.fightaging.org/archives/2021/12/isome...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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 m...
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This study nicely illustrates the importance of the cellular metabolic state of myeloid cells: it highlights that not only the availability of glucose, but also its channeling into different pathways (glycolysis versus glycogen synthesis) contributes to maintaining proper myeloid function. On the Ability of Redundant Blood Vessels to Lower Cardiovascular Mortality https://www.fightaging.org/archives/2021/11/on-the-ability-of-redundant-blood-vessels-to-lower-cardiovascular-mortality/ A few strategies offer the possibility of growing additional redundant blood vessels, though this is far from rigorously pr...
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This article will review the relationship between diabetes mellitus and AD as it relates to tau pathology. More understanding of the link between diabetes mellitus and AD could change the approach researchers and clinicians take toward both diseases, potentially leading to new treatments and preventative strategies in the future. Signaling from White Fat Tissue Contributes to Age-Related Hair Follicle Dysfunction https://www.fightaging.org/archives/2021/11/signaling-from-white-fat-tissue-contributes-to-age-related-hair-follicle-dysfunction/ Changes in fat tissue behavior in the skin take place with age, ...
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Mol Biol Rep. 2021 Nov 3. doi: 10.1007/s11033-021-06890-0. Online ahead of print.ABSTRACTAlzheimer's disease (AD), acknowledged as the most common progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. The characteristic pathologic hallmarks of AD-including the deposition of extracellular senile plaques (SP) formation, intracellular neurofibrillary tangles, and synaptic loss, along with prominent vascular dysfunction and cognitive impairment-have been observed in patients. Fibroblast growth factors (FGFs), originally characterized as angiogenic factors, are a large family of signaling mole...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Source Type: research
This study confirmed that the PSI could be a quantitative index of vascular aging and has potential for use in inferring arterial stiffness with an advantage over the rAIx. A Profile of Michael Greve and the Segment of the Longevity Industry that He Supports https://www.fightaging.org/archives/2021/10/a-profile-of-michael-greve-and-the-segment-of-the-longevity-industry-that-he-supports/ Would that the popular media produced more popular science articles about the longevity industry like this one. It is not just a profile of someone trying to make a difference in the world by advancing the state of medici...
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In this study, we performed RNA sequencing of microglia isolated from three representative neurodegenerative mouse models, AppNL-G-F/NL-G-F with amyloid pathology, rTg4510 with tauopathy, and SOD1G93A with motor neuron disease. In parallel, gene expression patterns of the human precuneus with early Alzheimer's change (n = 11) and control brain (n = 14) were also analyzed by RNA sequencing. We found that a substantial reduction of homeostatic microglial genes in rTg4510 and SOD1G93A microglia, whereas DAM genes were uniformly upregulated in all mouse models. The reduction of homeostatic mi...
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