The Rhyothemis princeps Brain Externalization Project

 There are a number of research programs that study interventions for increasing lifespan and healthspan in animals (dogs, mice, flies, nematode worms) with the aim of finding successful interventions that could be translated to humans. The Dog Aging Project enrolls companion dogs in observational and interventional studies on aging; it seems a worthwhile endeavor even if treatments are not applicable to humans as improving the lifespan and healthspan of dogs is worthwhile for its own sake. To date, however, there has not been a similar project for cats - or has there?  I watch a lot of cat videos and came upon one that reported ultra-longevity in a number of cats apparently achieved through diet and lifestyle interventions implemented by their human companion, Jake Perry. It seems strange that I learned about this from a cat video rather than through all the longevity-related media I consume. https://youtu.be/CXGCJeH4e-w?t=32   An article by Christina Couch published in Atlas Obscura

Yesterday I watched two introductory videos on the ubiquitin-proteasome system - very important in autoimmunity, aging, cancer and neurodegeneration. Alfred Goldberg, Functions of the proteasome, R&D Systems,  recorded February 4, 2016:  Index: 9:30 start of presentation 13:20 ubiquitin-proteasome pathway summary slide - ATP required 15:22 antigen presentation - 1% of product peptides are taken up by ER and displayed in cell surface by MHC class I molecules - proteasome allows immune system to screen intracellular space for abnormal proteins (pathogen or cancer) 23:16 multiple ATP dependent steps in proteasome function 38:00 Bortezmib - proteasome inhibitor, inhibits NF-kB, does not cross BBB, induces apoptosis 40:33 Endoplasmic-reticulum-associated protein degradation (ERAD) pathway is unusually activated in multiple myeloma cells ; proteasome inhibition results in increased ER stress and triggers UPR, further UPR activation triggers apoptosis 42:30 proteasome inhib

The eat 'five a day' (referring to servings of fruits and vegetables) recommendation of the World Health Organization and many national health agencies has new support based on findings by Wang et al. (2021) from the Nurses' Health Study and the Health Professionals Follow-up Study.   - link to open access article: https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.048996 The study found a reduction in all-cause mortality as well as reductions in mortality due to respiratory diseases, cardiovascular disease and cancer. The thresholds for reductions in mortality were achieved at two servings of fruit and three servings of vegetables per day. No additional benefit was seen for over five servings. Sadly, there was no significant reduction found for neurodegenerative diseases (but see the Michley et al. (2017, open access) study on Parkinson disease re: fresh vs. canned/frozen). Wang et al. (2021) Above is Figure 1 from Wang et al. (2021); it is quite small and th

A clinical trial [ Veterans Affairs Topical Tretinoin Chemoprevention Trial (VATTC)] of topical all-trans retinoic acid (tretinoin, Retin-A) had to be halted because the intervention arm experienced higher mortality. The authors indicate that a causal relationship is unlikely, but the finding is a bit troubling nonetheless. The increase in mortality was not attributable to any one specific cause of death. https://jamanetwork.com/journals/jamadermatology/fullarticle/711869 "We considered the possibility that topical tretinoin applied to the face and ears might be a cause of death. One study that was published during our trial involved systemic administration of isotretinoin, a closely related compound. That trial found a significant interaction between the medication and smoking in their effect on mortality, with isotretinoin therapy associated with increased mortality among smokers. 4 Studies involving a less closely related compound, beta carotene, have also suggested an

Glucosamine (credit: AndresJS )   Sometimes I lurk on various life extension message boards and am perplexed that many (most?) people do not list glucosamine in their pro-longevity 'stack' even though its use is associated with reduction in all-cause mortality. Glucosamine is cheap and relatively well-tolerated. While association does not mean causation, the relationship has been found in several large epidemiological studies and holds up when controlling for various demographic factors; similar associations have not been found for other supplements - not even fish oil or vitamin D. There are some plausible mechanisms, which I don't have time to really get into, unfortunately. In brief, glucosamine inhibits glucose metabolism (see Ristow interview linked below) - which could have direct effects and also effects via the gut microbiome, increases hyaluronic acid production, and may have other effects relating to O-GlcNAcylation (that's what I'm most interested i

Dr Ruslan Medzhitov presented 'What is a disease' at the inaugural meeting of the International Society for Evolution, Medicine and Public Health held March 19-21, 2015. Interesting perspective on the causes of type 2 diabetes and diseases of aging. 9:13 Robustness, resilience and vulnerability   15:45 Anna Karenina Principle in Life History Theory - only one way an environment can be perfect and many ways it can be hostile   16:00 Homeostasis - Maintenance - Defense 17:58 taking out the garbage is not part of homeostasis, it's a function of maintenance   20:24 Extrinsic and Intrinsic Mortality - investment in maintenance programs is dictated by extrinsic mortality rates   32:00 systems that have adjustable set points are vulnerable to dysregulation example: insulin signalling pathway - change in glucose allocation to fetus in pregnancy or to immune system in infection "That built-in property to change the set point of the insulin system also makes it vulnerab

"Aquaporin water channels - from transfusion medicine to malaria" by Dr. Peter Agre Sept. 9, 2015 22:22 Rarity of AQP1 null mutants despite apparently limited effect on phenotype - at birth lung goes from being secretory organ to being absorptive, may be a critical point 25:46 AQP4 and blood brain barrier { not mentioned in lecture: Evidence that pericytes regulate aquaporin-4 polarization in mouse cortical astrocytes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223569/ }   26:54 AQP4 - accelerated brain damage   27:49 in many cases or stroke the individual succumbs not to the infarct, but to brain edema 30:04 Aquaporins, stress response , decline in function with aging   41:34 AQP7 and AQP9 - Glycerol Metabolism AQP7 - present in fat; water & glycerol permeation; suppressed by insulin; releases glycerol from fat catabolism during starvation AQP9 - present in liver; water, glycerol & urea permeation; facilitates hepatic glycerol uptake for gluconeogen

[2020-7-13] Someone posted about nocturia on HealthUnlocked's Parkinson's Movement forum and I replied with the  following (I don't think I can keep up with doing the reference properly, perhaps if it starts to really bother me I will edit): Apart from prostate and autonomic nervous system problems, one issue in aging related to nocturia might be loss of function of aquaporins. Aquaporins are membrane channels for water; though water can diffuse across cell membranes AQPs move water faster and are particularly important under stress conditions. AQP function declines with age and could contribute to many age-related health issues including reduction in blood brain barrier function. hindawi.com/journals/omcl/2... ncbi.nlm.nih.gov/pmc/articl... Oxytocin has some vassopressin-like activity and helps move AQP from inside the cell to the membrane surface when needed. jasn.asnjournals.org/conten... Oxytocin levels decline with age: ncbi.nlm.nih.gov/pmc/articl... The probiot

In the post on osteocalcin that I can never quite finish I paraphrased a review on the topic that suggested that undercarboxylated osteocalcin may be one of the anti-aging factors present in 'young blood'.  Heterochronic parabioss experiments - wherein the circulatory systems of an old and a young mouse are joined - have shown rejuvenating effects for the old mouse and some age-promotion in the young. This has lead to speculation that there are youth-promoting factors in the blood of the younger mouse that provide benefit to the older mouse.  However the Conboys and their research team, who pioneered heterochronic parabiosis experiments, have proposed that it is actually dilution of pro-aging factors that provides the age-reversing effects. They recently published an article [Mehdipour et al. 2020] showing dilution of the blood of an old mouse is sufficient for rejuvenation.  From the article: "The above concept fits well with the age-imposed increase in systemic TGF-beta

[2020-06-13] Talk by Kelvin J.A. Davies on Lon protease from 2013(?) 12:56 Degradation of oxidized proteins by proteasome is mostly ATP independent; degradation by Lon is ATP dependent   20:08 the most decreased mRNA in skeletal muscle in mice in aging is Lon 20:36 the main one that comes up is aconitase, but there are many, many others   20:17 Lon inducibility is diminished in senescent cells & they have more carbonylated proteins   22:20 slide - Aging Decreases Lon Induction and Stress Protection 26:28 Lon attaches to mtDNA and allows for biogenesis; under stress it detaches and degrades oxidized proteins and at that point proliferation stops   28:59 Lon is inducible by H2O2, heat stress, starvation, cold stress, mechanical shear stress, peroxynitrite Also, loss of frataxin upregulates Lon and ClpP proteases and results in too much degradation of Fe-S proteins [1]. 1 - Guillon, Blanche, Anne-Laure Bulteau, Marie Wattenhofer-Donzé, Stéphane Schmucker, Bertrand Friguet,

From a  discussion with OS on MedCram (which had gone way OT from sex differences relating to covid-19 pathology - link to discussion thread ): re: AMPK bat genetics - not much yet, but there's this one Positive Selection of Cereblon Modified Function Including Its E3 Ubiquitin Ligase Activity and Binding Efficiency With AMPK - https://pubmed.ncbi.nlm.nih.gov/30836149/ Note the same modification is present in both bats and rodents. Hamsters do seem to have some protection from oxidative stress, but they are not particularly long-lived as are bats. They are what's termed 'r selected' - with a life history characterized by high reproductive rate and short life-span. Here's an article that points out that oxidative stress defenses may be tissue specific and that hamsters may not have as much protection in the brain: Oxidative Damage Does Not Occur in Striped Hamsters Raising Natural and Experimentally Increased Litter Size - https://www.ncbi.

Aconitase (aconitate hydratase) is a tricarboxylic acid cycle (TCA) enzyme that converts citrate to iso-citrate via cis-aconitate. It has an iron sulfur cluster that interacts directly with substrate and is prone to oxidation by superoxide. Inactivation of aconitase has been  implicated in neurodegenerative diseases [1]. A mutation in ACO2 is associated with Infantile Cerebellar-Retinal Degeneration [2]. from [2] : "The active (4Fe-4S) cluster was shown to be extremely sensitive to superoxide-mediated inactivation 10 and a decrease in AH activity was observed in several neurodegenerative diseases associated with the development of oxidative stress, in particular Friedreich ataxia [MIM 229300 ], Parkinson [MIM 168600 ], and Alzheimer disease [MIM 104300 ], 11 as well as in mice lacking mitochondrial superoxide dismutase. 12 The reduced AH activity in endomyocardial biopsies of individuals with Friedreich ataxia was attributed not only to oxidative stress but also to the im