April 2020 Longevity Review

April 2020 Longevity Review

Hello and welcome again to this month’s longevity review. With the world caught in a virus standstill, thankfully science continues to trundle along in the background and results keep on being published. This month a potentially better senolytic has been invented, a means of lengthening telomeres found and a novel method to produce photoreceptors discovered among many other results.

For the past couple weeks I’ve been hit hard by corona lethargy, but just managed to find enough energy to put this month’s newsletter together. LEAF’s Ending Age Related Diseases 2020 (20-21 August) conference has also now gone online. I had expected to be in attendance as a volunteer, but hopefully I will still be able to contribute somehow.

Stay safe!

Follow me on Twitter @ChrisPollyanna1 for the latest updates.
Also, please join my longevity Facebook group.
Finally – if there are any comments or questions, please post them in the comment section below.
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NOTE: I’ve been having trouble linking to the science journal hacking site www.sci-hub.tw , so am only including Full Text links to articles not behind a paywall. I still have been able to download most of them, so if there are any that you are after, I can send them upon request, or you can simply copy the paper’s URL into the site above to get +95% of papers hidden behind paywalls.

April Round-Up:

I’ve long been hailing the destruction of senescent cells (senolytics) as the big thing in the longevity field, however, side effects can occur if non-senescent cells are also eliminated. Therefore it is paramount to improve the selectivity of senolytics, and this paper is an example of just that. Here, researchers created a new senolytic which is not only much more selective, but also more thoroughly cleared the senescent cells.

Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice. Full Text

Here, scientists have found a method to restore telomere length in stem cells, which can stop them from becoming dysfunctional. Although developed for specific telomere diseases, this method could have broader applicability to ageing, for example by preventing stem cell exhaustion and preserving their regenerative capacity.

Restoring Telomerase Activity in Patient Stem Cells Abstract

In this study, researchers have managed to partially restore vision in mice by turning regular cells into photoreceptors. This could be used to treat age related eye diseases such as AMD and diabetic retinopathy.

Fibroblasts Reprogrammed Into Photoreceptors Restore Vision Abstract

I’ve long gone on about the benefits of reducing calories or practicing intermittent fasting and this study is further evidence in its favour. This time fasting under Ramadan conditions was studied, where the participants went without food for at least 14 hours during the day (dawn until sunset). Following this for 30 days improved various health biomarkers including anti-cancer ones.

Intermittent Fasting Shows Multiple Health Benefits Full Text

To reinforce how lifestyle is still currently the number one means of delaying the onset of ageing related diseases, the following study put a number to it. Compared to those who followed best lifestyle practices, those who didn’t could expect to start suffering more than nine years earlier

Association of Healthy Lifestyle With Years Lived Without Major Chronic Diseases. Full Text

Finally a couple of papers on my favourite longevity hack - wheat germ, or more specifically the spermidine which it contains. Not only does it have a host of health benefits, but in the form of wheat germ is incredibly cheap and tasty to boot!

Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice. Full Text

Long-term treatment with spermidine increases health span of middle-aged Sprague-Dawley male rats.

Covid-19 Longevity Related Papers:
A Novel Combination of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from System Biology Analysis.

2020 Supplemental Information

***Disclaimer 1 – As should be self-evident to anyone receiving these emails, I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if needing medical advice.***

**Disclaimer 2 – In no way should supplements be a replacement for an unhealthy diet or lifestyle. A varied, plant dominant dietary pattern is the cornerstone for health. Try to eat the rainbow – the greater the variety, the greater the benefit. Even though I might take a supplement derived from a plant source, I still eat the plant in question. Also, make sure you move as much as possible – that is what we evolved to do.**

*Also bear in mind that most of the studies mentioned below are in rodents, not humans. Rodents, needless to say, do not always react the same way to drugs as humans do – witness the countless times cancer or another disease has been cured in rodents only to subsequently fail human trials. I have *bolded any human trials.*
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Lifestyle

Fasting/Dietary Restriction – certainly the cheapest & also one of the most effective anti-ageing interventions currently available. It comes in many flavours, but I fast for at least 12 hours every day.
Caloric restriction reverses left ventricular hypertrophy through the regulation of cardiac iron homeostasis in impaired leptin signaling mice. Full Text
Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms. Full Text
*12 days of in vivo caloric reduction can improve important parameters of aging in humans.

Diet – let food be thy medicine…
*Coffee consumption and mortality from cardiovascular diseases and total mortality: Does the brewing method matter? Full Text
*Adherence to the Mediterranean Diet in Spanish Population and Its Relationship with Early Vascular Aging according to Sex and Age: EVA Study. Full Text
*Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort. Full Text
Are ketogenic diets promising for Alzheimer's disease? A translational review. Full Text
Extra-Virgin Olive Oil from Apulian Cultivars and Intestinal Inflammation. Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Effects of High Intensity Resistance Training on Osteopenia and Sarcopenia parameters in Older Men with Osteosarcopenia - One-year results of the randomized controlled Franconian Osteopenia and Sarcopenia Trial (FrOST).
*The influence of prolonged strength training upon muscle and fat in healthy and chronically diseased older adults.
*Combined Black Rice Germ, Bran Supplement and Exercise Intervention Modulate Aging Biomarkers and Improve Physical Performance and Lower-Body Muscle Strength Parameters in Aging Population. Full Text
Swimming exercise stimulates IGF1/ PI3K/Akt and AMPK/SIRT1/PGC1α survival signaling to suppress apoptosis and inflammation in aging hippocampus. Full Text

Non-prescription Supplements (in alphabetical order)
*Due to concerns about engendering homeostasis, I’ve begun varying my intake of supplements so that I’m not taking all of them every day. Haven’t worked out a rota so far.

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotinoid, it has anti-oxidative, anti-inflamatory, anti-cancer, neuro-protective and skin-protective qualities. I take 4 or 8 mg intermittently.
Therapeutic Effect of Seaweed Derived Xanthophyl Carotenoid on Obesity Management; Overview of the Last Decade. Full Text
Astaxanthin alleviates gestational diabetes mellitus in mice through suppression of oxidative stress.
Astaxanthin suppresses endoplasmic reticulum stress and protects against neuron damage in Parkinson's disease by regulating miR-7/SNCA axis.
Astaxanthin attenuates d-galactose-induced brain aging in rats by ameliorating oxidative stress, mitochondrial dysfunction, and regulating metabolic markers.
Astaxanthin Attenuates Hypertensive Vascular Remodeling by Protecting Vascular Smooth Muscle Cells from Oxidative Stress-Induced Mitochondrial Dysfunction. Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. I take 1 gram intermittently. Needs to be taken with black pepper (piperine) to improve bio-availability.
*Dietary Supplementation with Curcumin Reduce Circulating Levels of Glycogen Synthase Kinase-3β and Islet Amyloid Polypeptide in Adults with High Risk of Type 2 Diabetes and Alzheimer's Disease. Full Text
*Influence of curcumin on performance and post-exercise recovery.
*Effects of curcumin supplementation on sport and physical exercise: a systematic review.
*Influence of curcumin on glycemic profile, inflammatory markers, and oxidative stress in HIV-infected individuals: A randomized controlled trial.

Melatonin – a natural hormone produced in the pineal gland, it makes us get to sleep every night, but it has many other functions, including as a mitochondrial anti-oxidant. I’ve been taking 3mg for years before bed time purely as a sleep aid, but I’ve recently noticed it repeatedly cropping up in my longevity searches so decided to include it in its own section.
*The association between melatonin and episodic migraine: a pilot network meta-analysis of randomized controlled trials to compare the prophylactic effects with exogenous melatonin supplementation and pharmacotherapy.
Melatonin inhibits vascular smooth muscle cell proliferation and apoptosis through upregulation of Sestrin2. Full Text
Melatonin: new insights on its therapeutic properties in diabetic complications. Full Text
Melatonin improves mitochondrial biogenesis through the AMPK/PGC1α pathway to attenuate ischemia/reperfusion-induced myocardial damage. Full Text

Nicotinamide Riboside (NR) – NAD+ precursor.
*Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. Full Text
The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alc33oholic fatty liver disease. Full Text
Targeting sirtuin activity with nicotinamide riboside reduces neuroinflammation in a GWI mouse model.
NAD+ Controls Circadian Reprogramming through PER2 Nuclear Translocation to Counter Aging.

Pterostilbene – found in blueberries. Anti-oxidant, anti-inflamatory and Sir1 activator. Similar to, but with greater bioavailability than resveratrol. Taking 50mg intermittently in the same pill as resveratrol. Works better in conjunction with NAD+ precursors.
The Preventive Effects of Pterostilbene on the Exercise Intolerance and Circadian Misalignment of Mice Subjected to Sleep Restriction.

Resveratrol – found in the skin of grapes. Anti-oxidant, anti-inflamatory and Sir1 activator. Taking 250mg intermittently in the same pill as pterstilbene. Works better in conjunction with NAD+ precursors & Spermidine.
Resveratrol restores intracellular transport in cystic fibrosis epithelial cells.
Resveratrol restores intracellular transport in cystic fibrosis epithelial cells. Full Text
Resveratrol reduces obesity in high-fat diet-fed mice via modulating the structure and metabolic function of the gut microbiota.
Neuroprotective Properties of Resveratrol and Its Derivatives-Influence on Potential Mechanisms Leading to the Development of Alzheimer's Disease. Full Text
Effect of resveratrol on intestinal tight junction proteins and the gut microbiome in high-fat diet-fed insulin resistant mice.

Spermidine – found in wheat germ and a potent inducer of autophagy, it works in synergy with Resveratrol. I try to eat a few of teaspoons of wheat germ every day in my berry & nut breakfast.
Spermidine rescues the deregulated autophagic response to oxidative stress of osteoarthritic chondrocytes. Spermidine Suppresses Development of Experimental Abdominal Aortic Aneurysms. Full Text

Other available supplements
Astragaloside IV inhibits astrocyte senescence: implication in Parkinson's disease. Full Text
Coenzyme Q10: Clinical Applications in Cardiovascular Diseases. Full Text
Lower tumorigenesis without life extension in rats receiving lifelong deep ocean minerals. Full Text
Quercetin ameliorates diabetic encephalopathy through SIRT1/ER stress pathway in db/db mice. Full Text
Vitamin C Treatment Rescues Prelamin A-Induced Premature Senescence of Subchondral Bone Mesenchymal Stem Cells. Full Text

Prescription Supplements

Metformin – Anti-diabetic medication, maintained by many scientists to be a safe longevity enhancing medication. I’m still on the fence about this.
Myotonic Dystrophy type 1 cells display impaired metabolism and mitochondrial dysfunction that are reversed by metformin. Full Text
Metformin rescues rapamycin-induced mitochondrial dysfunction and attenuates rheumatoid arthritis with metabolic syndrome. Full Text
The protective role of metformin in autophagic status in peripheral blood mononuclear cells of type 2 diabetic patients.
Metformin Improves Cardiac Metabolism and Function, and Prevents Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats. Full Text
Metformin Prevents H₂O₂-Induced Senescence in Human Lens Epithelial B3 Cells. Full Text

Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer.
Rapamycin rejuvenates oral health in aging mice. Full Text
Rapamycin restrains platelet procoagulant responses via FKBP-mediated protection of mitochondrial integrity.
Accumulation of prelamin A induces premature aging through mTOR overactivation. Full Text
Dietary and Pharmacological Interventions that Inhibit Mammalian Target of Rapamycin (mTOR) Activity Alter the Brain Expression Levels of Neurogenic and Glial Markers in An Age- and Treatment-Dependent Manner.
Blockade of the mTOR signaling pathway with rapamycin ameliorates aristolochic acid nephropathy. Full Text

Other Areas of Interest

Senolytics – not supplements or available now, but the most exciting area of anti-research at the moment. I intend to take the plunge into senolytics within the next year, before giving them to my parents:
An Appraisal on the Value of Using Nutraceutical Based Senolytics and Senostatics in Aging. Full Text
Targeting senescent cells to attenuate cardiovascular disease progression. Full Text
Insights from In Vivo Studies of Cellular Senescence. Full Text
A multidimensional systems biology analysis of cellular senescence in aging and disease. Full Text
Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity. Full Text

Epigenetic Cellular Reprogramming– the next big thing in longevity science as far as I am concerned & the closest thing we might have to a silver bullet against ageing. It involves targeting the epigenome:
Fibroblast rejuvenation by mechanical reprogramming and redifferentiation. Full Text

Ageing Clocks & other biomarkers of ageing – the ability to measure biological ageing is crucial if we don’t want to have to wait 20+ years for the results of an anti-ageing intervention:
Systematic review and analysis of human proteomics aging studies unveils a novel proteomic aging clock and identifies key processes that change with age.
Systematic age-, organ-, and diet-associated ionome remodeling and the development of ionomic aging clocks. Full Text
Biohorology and biomarkers of aging: current state-of-the-art, challenges and opportunities. Full Text
Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield.

Telomeres – the protective caps on the end of our chromosomes. Their shortening over time has been seen by some as either an ageing “clock”, or indeed as a driver of ageing itself, however, this is a controversial viewpoint.
Telomere shortening associates with elevated insulin and nuchal fat accumulation.

Microbiome – all the little critters living in and on us have a major influence on our health and potentially our longevity.
Probiotics Alleviate the Progressive Deterioration of Motor Functions in a Mouse Model of Parkinson's Disease. Full Text
A human-origin probiotic cocktail ameliorates aging-related leaky gut and inflammation via modulating microbiota-taurine-tight junction axis. Full Text

Stem Cells & Exosomes (small packets of information released by cells)
Mechanisms and rejuvenation strategies for aged hematopoietic stem cells. Full Text
Regeneration of pulpo-dentinal-like complex by a group of unique multipotent CD24a+ stem cells. Full Text
Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell-Macrophage Interaction. Full Text
Bone marrow mesenchymal stem cells transplantation alleviates brain injury after intracerebral hemorrhage in mice through the Hippo signaling pathway. Full Text

Young Blood Factors or other heterochronic transplantation – another potential “silver bullet” against ageing based on the discovery that young blood seems to rejuvenate older animals and vice versa. The race is on to discover what components in blood cause these changes and if they can be applied to humans:
Heterochronic parabiosis regulates the extent of cellular senescence in multiple tissues.

Skin & Beauty – not naming any names, but I’m sure that some of you also care about superficial ageing – how our skin looks. ;-) Having said that, it is our largest organ & the treatments which keep on cropping up could be of use to some people.
CO2 lattice laser reverses skin aging caused by UVB.

Odds & Sods
A cellular surveillance and defense system that delays aging phenotypes in C. elegans. Full Text
Shorter life and reduced fecundity can increase colony fitness in virtual Caenorhabditis elegans. Full Text
Klotho antagonizes pulmonary fibrosis through suppressing pulmonary fibroblasts activation, migration, and extracellular matrix production: a therapeutic implication for idiopathic pulmonary fibrosis. Full Text
The neuronal receptor tyrosine kinase Alk is a target for longevity. Full Text
Neurostimulation techniques to enhance sleep and improve cognition in aging. Full Text
A Preliminary Study to Investigate the Genetic Background of Longevity Based on Whole-Genome Sequence Data of Two Methuselah Dogs. Full Text
S-Phase Kinase-associated Protein-2 Rejuvenates Senescent Endothelial Progenitor Cells and Induces Angiogenesis in Vivo. Full Text
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