Ayy /fit/, here are the latest anti-aging papers that our favorite molecularly-challenged middle-aged hypothermia babby should be reading:>S100A8/A9 as a central hub in inflammaging: Cross-system mechanisms>https://www.sciencedirect.com/science/article/pii/S1568163726001005>The IGF-1 senescence switch: a biphasic model for SASP-driven aging and precision senomodulation>https://www.sciencedirect.com/science/article/abs/pii/S1043466626000384>Dasatinib and quercetin prevent alveolar bone loss in aged mice>https://aap.onlinelibrary.wiley.com/doi/full/10.1002/jper.70115>The chemically defined herbal mixture ADAPT-232 delays mitochondrial dysfunction and promotes healthspan through mitophagy-related pathways mediated by the DAF-16/NHR-49 axis>https://www.sciencedirect.com/science/article/pii/S0944711326003521>Senolytic therapy ameliorates high-fat diet-induced hippocampal senescence and cognitive decline in mice>https://www.sciencedirect.com/science/article/abs/pii/S0014488626001081>Senolytic effects of Moringa oleifera leaf extract in an in vitro model of Alzheimer’s disease>https://www.researchsquare.com/article/rs-9082466/v1>Vascular Calcification Regulated by Klotho During Physiological and Pathophysiological Aging>https://hrcak.srce.hr/file/499227>WCN26-2852 Effects of senolytic drugs on kidney tissue in aged mice>https://www.kireports.org/article/S2468-0249(26)01956-X/fulltext>Shenrong Guben Huanshao Wan extract reduces Aβ-induced toxicity in the Caenorhabditis elegans model of Alzheimer’s disease via SKN-1/NRF2 pathway>https://www.sciencedirect.com/science/article/pii/S2667142526000461>Polysaccharide SP-3 derived from Saposhnikovia divaricata (Turcz.) Schischk. enhances immunity by regulating intestinal targets and gut microbiota>https://www.sciencedirect.com/science/article/pii/S0944711326003600
>>77184002Diflunisal, a salicylic acid derivative, increases NAD+ levels by ACMSD inhibition.>Diflunisal Derivatives as Modulators of ACMS Decarboxylase Targeting the Tryptophan Kynurenine Pathwayhttps://pmc.ncbi.nlm.nih.gov/articles/PMC7856275/In the kynurenine pathway for tryptophan degradation, an unstable metabolic intermediate, α-amino-β-carboxymuconate-ε-semialdehyde (ACMS), can nonenzymatically cyclize to form quinolinic acid, the precursor for de novo biosynthesis of NAD+. In a competing reaction, ACMS is decarboxylated by ACMS decarboxylase (ACMSD) for further metabolism and energy production. Therefore, the inhibition of ACMSD increases NAD+ levels. In this study, an FDA-approved drug, diflunisal, was found to competitively inhibit ACMSD. The complex structure of ACMSD with diflunisal revealed a previously unknown ligand-binding mode and was consistent with results of inhibition assays, as well as a structure-activity relationship (SAR) study. Moreover, two synthesized diflunisal derivatives showed IC50 values one order of magnitude better than diflunisal at 1.32 ± 0.07 μM (22) and 3.10 ± 0.11 μM (20), respectively. The results suggest that diflunisal derivatives have the potential to modulate NAD+ levels. The ligand-binding mode revealed here provides a new direction for developing inhibitors of ACMSD.
>>77184019Another interesting thing about this drug is that it can reduce amyloid plaque formation all around the body, and is currently researched for alzheimers disease.
>>77184002Do you think there's any way of replicating this in humans?>Born to run; the story of the PEPCK-Cmus mousehttps://pmc.ncbi.nlm.nih.gov/articles/PMC2491496/In order to study the role of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-C) in skeletal muscle, PEPCK-Cmus mice were created by introducing the cDNA for the enzyme, linked to the human α-skeletal actin gene promoter, into their germ line. Two founder lines generated by this procedure were bred together, creating a line of mice that have 9.0 units/g skeletal muscle, as compared to 0.080 units/g in muscle from control animals. The mice were more active than controls in their cages and could run for up to 5 km, at a speed of 20 m/min without stopping (control mice run for 0.2 km at the same speed). Male PEPCK-Cmus mice are extremely aggressive, as well as hyperactive. During strenuous exercise, they use fatty acids as a fuel more efficiently than do controls and produce far less lactate than do control animals, perhaps due to the greatly increased number of mitochondria in their skeletal muscle. PEPCK-Cmus mice also store up to five-times more triglyceride in their skeletal muscle, but have only marginal amounts of triglyceride in their adipose tissue depots, despite eating 60% more than controls. The concentration of leptin and insulin the blood of 8 to 12 month of PEPCK-Cmus mice is far lower than noted in the blood of control animals of the same age. These mice live longer than controls and the females remain reproductively active for as long as 35 months. The possible reasons for the profound alteration in activity and longevity caused the introduction of a simple metabolic enzyme into the skeletal muscle of the mice will be discussed.
>>77184024Related papers:>Reciprocal Changes in Phosphoenolpyruvate Carboxykinase and Pyruvate Kinase with Age Are a Determinant of Aging in Caenorhabditis eleganshttps://pubmed.ncbi.nlm.nih.gov/26631730/>Gluconeogenesis and PEPCK are critical components of healthy aging and dietary restriction life extensionhttps://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008982
>>77184002>Protein Overfeeding is Associated with Improved Lipid and Anthropometric Profile thus Lower Malondialdehyde Levels in Resistance-Trained Athleteshttps://www.researchgate.net/publication/317050180_Protein_Overfeeding_is_Associated_with_Improved_Lipid_and_Anthropometric_Profile_thus_Lower_Malondialdehyde_Levels_in_Resistance-Trained_Athletes
>Reduced fertility induced by MASLD in female mice is improved by Senolytic treatment>https://academic.oup.com/biolreprod/advance-article-abstract/doi/10.1093/biolre/ioag060/8534429>SMN-independent amelioration of spinal muscular atrophy by pharmacological inhibition of JNK >https://doi.org/10.1093/braincomms/fcag111>The Conjugated Bile Acids Profile Suggests a Novel Liver-Muscle Axis Associated With Sarcopenia in Chronic Liver Disease>https://onlinelibrary.wiley.com/doi/full/10.1111/liv.70612>Multi-Omics and Machine Learning Reveal a Critical Mediator of PRKCA in Quercetin-Mediated Protection Against Sarcopenia>https://www.sciencedirect.com/science/article/pii/S0944711326003569>Sea Cucumber Collagen Peptides Exert an Anti-Skin Aging Effect by Inhibiting Endoplasmic Reticulum Stress in Fibroblasts>https://www.mdpi.com/2304-8158/15/7/1147>Investigation of Some Anti-Aging Effects of Pterostilbene in Schizosaccharomyces pombe>https://link.springer.com/article/10.1134/S0026261725604221>Valorization of Pistacia lentiscus L. Hydrodistillation By-Products: Phytochemical Profile and Multitarget Anti-Aging Activity of an Aqueous Extract>https://www.mdpi.com/2223-7747/15/7/1013>The Sirt2–Nur77 axis regulates muscle stem cell quiescence and senescence via epigenetic–metabolic synergy>https://www.nature.com/articles/s41419-026-08645-w>Epigenetic aging is a hallmark of HIV pathogenesis and phenotypic outcomes>https://link.springer.com/article/10.1007/s11904-026-00781-4>>77184019>>77184022Damn, the aspirin derivatives keep getting more and more deranged, nice find!>>77184024Here are some small molecules, but the corticosteroids are obviously known gainz goblinz overall:>https://www.scbt.com/browse/pepck-c-activators>>77184041I wouldn't get too carried away with the protein overfeeding though; can get into foamy piss territory and eventually kidney damage unless your nephroprotective skills are S-tier.
Call us when all that suit has been tested on human and there are ręplicated studies with the same result.Almost anything increases lifespan in rats. A control group is kept in such conditions, that any change in diet will result in an extenfed lifestyle.
>>77185112>A control group is kept in such conditions, that any change in diet will result in an extenfed lifestyle.What do you mean?
>>77184002>>77184019>>77184024>>77184051Post physique
>>77185191>Post physique195cm/100kg
>>77185196The medicine is shrinking your penis and giving you tits. Out of good will and intentions, cut that crap and go lift weight and eat meat. That's all you need, there's no shortcut.
>>77184002>Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.https://europepmc.org/article/MED/26936358
>Mice study>in Vitro>Mice study>in Vitro>Mice study>in VitroFucking garbage. Come back when you have actual human studies.
>>77185196Nyle red?
>>77185196Holy shit dude your dick is enormous. Mirin hard
>>77185288Yeah it goes up to his belly button damn impressive
>>77184002Biojew-kun, have you researched anti-aging properties of carbonic anhydrase inhibitors, such as acetazolamide?>Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegenerationhttps://www.aging-us.com/article/101064/text
>>77185314
>>77184002>>77185314>>77185318>Aspirin: A Suicide Inhibitor of Carbonic Anhydrase IIhttps://pmc.ncbi.nlm.nih.gov/articles/PMC7226357/>This data may also explain the short half-life of Aspirin, with CAII so abundant in blood, and that Aspirin could act as a suicide inhibitor of CAII.Carbonic anhydrase II inhibitors + Aspirin... Looks like a very powerful synergy to me.
>>77185405>we provide kinetic data to support the observation that CAII converts Aspirin to its deacetylated form, SA.
>>77185405Amino Acids. 2026 Feb 6;58(1):11. doi: 10.1007/s00726-026-03501-9>Unveiling the anti-glycation properties of acetylsalicylic acid: targeted inhibition of albumin glycationhttps://pmc.ncbi.nlm.nih.gov/articles/PMC12904887/
>>77184002supplement autists in this thread:Peatards on twitter suggest that Aspirin can be a powerful pro-lean mass chemical, something to do with pain mediation without reducing muscle inflammation and somehow acts to boost DHT, is this true?If I take it the day before a workout I feel like a lose strength but otherwise I tolerate it well.
>>77186796Aspirin will enhance muscle recovery by enhanced inflammation resolution due to generation of aspirin-triggered lipoxins in damaged tissue that prevent further inflammatory damage and clear cellular debris, but it should be taken only after workout and not before, otherwise if will cause inflammation inhibition and not resolution. At higher doses it acts as mild mitochondrial uncoupler (like DNP), but it can cause gastric and cochlear damage, so if you take it in high doses you shall drink it with ginger (to protect your gut) and glycine/collagen (to get rid of salicylic acid that damages hearing nerves). Recent research suggests It's effects will be greatly amplified by Carbonic Anhydrase II inhibiting diuretics such as acetazolamide by prolonging it's half-life and reducing toxicity by reducing it's conversion to salicylic acid.
>>77184002Niacinamide serves as a methyl sink and consumes methionine, thus mimicking methionine restriction/deficiency. >Steroid-dependent metabolic rewiring reveals novel therapeutic and imaging approaches for glioblastomahttps://pmc.ncbi.nlm.nih.gov/articles/PMC12829581/Steroid anti-inflammatory drugs, such as dexamethasone, are routinely used to manage brain tumor–associated edema, yet their impact on brain tumor metabolism remains understudied. Here, a metabolomic screen in naïve glioblastoma cells treated with dexamethasone revealed the accumulation of N1-methylnicotinamide, a nicotinamide N-methyltransferase (NNMT) product, through glucocorticoid receptor activation. Using stable isotope-assisted metabolomics in patients with glioblastoma, we showed that nicotinamide conversion into N1-methylnicotinamide exceeds that into NAD+, leading to a ~7-fold accumulation of N1-methylnicotinamide in tumor compared to surrounding brain tissue. In orthotopic models, NNMT activity was enhanced by dexamethasone selectively in glioblastoma tumors but not in contralateral brain. Leveraging the tumor-specific activity of NNMT, we developed a novel 11C-nicotinamide–based positron emission tomography (PET) approach to visualizing glioblastoma tumors. Furthermore, our findings demonstrate that the dexamethasone-induced methionine-dependent nicotinamide methylation becomes detrimental for glioblastoma when combined with a methionine-restricted diet. These results show that steroids rewire methionine and nicotinamide metabolism, enabling the development of innovative PET imaging and metabolic therapies for glioblastoma.
>>77184002Genes Passed Down from Fallen AngelsThe serotonin transporter long-allele.The "Warrior-Gene".DAT1 Mutation.DRD2 TAq1A Mutation.***Origins***The long-allele of the serotonin transporter originates in Denmark- and was passed down by the Vikings.The Warrior Gene originates among the Maori people - who privately reproduced with fallen angels.The DAT1 mutation comes from Denmark - most likelyAzazelbeing the bearer of the geneThe DRD2 TAq1A mutation comes from Denmark as well.***EFFECTS***Thelong alleleneurotransmitter gene makes one "stress-resistant" in the face of negative stimuli - sometimes also referred to as stress immunity - and is a characteristic of Psychopaths. It also makes the person have lower Serotonin levels.The Warrior-Gene makes you have higher brain concentrations of Dopamine, Norepinephrine & Serotonin.The DAT1 mutation leaves more Dopamine in the Brain rather than being removed from use.The DRD2 TAq1A mutation leaves less Dopamine D2-receptors (autoreceptors) in the Brainleading to obsessive sexual desire& higher fertility rates, resistance to antipsychotic medication induced infertilityas well as less Depression.
>>77189030>The "Warrior-Gene".You can basically get the upsides with a little bit of MAO-A inhibition, but not too much. Bryan Johnson overdoses on methylene blue to where he might die from ripe fruits.
What can I take to stop being an alcoholic? Any magical cure to make me want to stop drinking?
>>77189597There's many things. One of the healthiest is dutasteride.
>>77189620I will look into it but it seems to need several months to start working. I did naltrexone, acamprosate, antabuse too and they didn't work on me. What else is there?
>>77189629Everything is going to take several months as you need to clear ΔFosB which has a long as fuck half life to cure addictive behavior.You could try to increase AMPK and shut off mtor to speed it up a bit
>>77189675What do you think about OCD? I've heard NAC has an impact but I've been taking it for a year without any clear benefit
