May 2020 Longevity Review

May 2020 Longevity Review

The big news from me is that the program for Ending Age Related Disease 2020 has been released, and what a stellar lineup it is! It is a veritable who’s who of the longevity research community. If you’ve never attended a longevity conference before, this is the perfect opportunity to break your duck, as not only can you do so from the comfort of your home, but it is also eminently affordable. In fact, there is even a free option, which gives you access to the keynote speeches as well as a biotech startup seminar hosted by Ichor’s Kelsey Moody. I will once again be volunteering at this conference.
Follow me on Twitter @ChrisPollyanna1 for the latest news.
It would also be great if you joined my longevity Facebook group.
Finally – please share your thoughts and feedback in the comments section at the bottom.
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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.
May Round-Up:

• I’m usually reticent in publishing details of studies which have not been peer reviewed; however, sometimes the results are so potentially groundbreaking that I can’t hold back. This study falls into that category. Here, an undisclosed plasma fraction was used to reverse the age of rats back to a youthful level. I initially disclosed parts of this study in my February 2019 Review, where various biomarkers, such as those for inflammation, returned to the levels of younger rats. This new extension took things a step further by checking the epigenetic age of the rats in various tissues after treatment, which resulted in an average age reduction of 54%. Extraordinary.

And especially due to the extraordinary nature of these results, I need to add a few caveats. Firstly, as mentioned before, it has now yet been peer reviewed. Secondly, it used an extremely small cohort of rats (6). Thirdly, a lifespan study has not yet been completed. However, the fact that Steve Horvath, who is the leader in epigenetic age testing, is a co-author lends a considerable amount of credence to the results. My fingers are definitely crossed on this one!

Blood Factors Reverse Epigenetic Age by Half in Rats Full Text

Very positive interpretation from Josh Mittledorf: Age Reduction Breakthrough

LEAF Journal Club video on the study

• Almost the reverse of the above study is the one below from the Conboys, who believe that factors in old blood can overpower any benefits from youthful factors. Here they simply diluted old blood by replacing 50% of it with saline and albumin (5%) which resulted in some rejuvenation. If this holds water, it would be easily translatable to humans as plasma exchange is an established medical procedure.

Rejuvenation of Three Germ Layers Tissues by Exchanging Old Blood Plasma With Saline-Albumin Full Text

Josh Mittledorf’s take: Out With the Old Blood

• It is my opinion that a combination of the two approaches is most likely to work best, but of course that experiment still needs to be done before reaching any conclusions. For more studies of this ilk, check out the Young Blood Factors section in the Supplemental Information below.

• Here is yet another strategy for clearing senescent cells, this time using our own immune system via a vaccine. Although this was only used to clear senescent T-cells, since our bodies naturally clear some senescent cells, a therapy harnessing this nascent power would be most beneficial.
• The CD153 Vaccine Is a Senotherapeutic Option for Preventing the Accumulation of Senescent T Cells in Mice Full Text

• In this study gene editing was used to improve muscle wasting, a serious problem for the elderly, in mice by targeting myostatin.

Improvement of Muscular Atrophy by AAV-SaCas9-mediated Myostatin Gene Editing in Aged Mice Full Text

• Finally, stem cells were used to repair ageing bone marrow and thereby aslo increase its antioxidant capacity and improve immune function.

Mesenchymal Stem Cells Repair Bone Marrow Damage of Aging Rats and Regulate Autophagy and Aging Genes

Covid-19 Longevity Related Papers:

Why Does COVID-19 Disproportionately Affect Older People? Full Text
An Update on Current Therapeutic Drugs Treating COVID-19 Full Text
*COVID-19: Patients improve after heart cell therapy Full Text
Potential Effects of Curcumin in the Treatment of COVID-19 Infection Full Text
The Role of Vitamin D in the Prevention of Coronavirus Disease 2019 Infection and Mortality Full Text
Indomethacin and Resveratrol as Potential Treatment Adjuncts for SARS-CoV-2/COVID-19 Full Text
Targeting T-cell Senescence and Cytokine Storm With Rapamycin to Prevent Severe Progression in COVID-19 Full Text
Immunoregulation With mTOR Inhibitors to Prevent COVID-19 Severity: A Novel Intervention Strategy Beyond Vaccines and Specific Antiviral Medicines Full Text

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Video to watch:
A couple of interviews here brought to you by LEAF taking a look at the latest in longevity research. The first interview is with Aubrey de Grey, head of the SENS Research Foundation and leading longevity advocate for almost 20 years. The second is with Alex Zhavoronkov, CEO of Insilico Medicine, who are looking at machine learning and AI to speed up drug discovery.
Interview with Aubrey de Grey: Updates on Aging Research in the Age of COVID-19
Interview with Alex Zhavoronkov: A.I. Drug Discovery to Fight Aging and COVID-19
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2020 Supplemental Information

Diet – let food be thy medicine…
*Effects of Vegetarian Diets on Blood Pressure Lowering: A Systematic Review With Meta-Analysis and Trial Sequential Analysis Full Text
*Effects of Polyphenol-Rich Interventions on Cognition and Brain Health in Healthy Young and Middle-Aged Adults: Systematic Review and Meta-Analysis Full Text
*Targeted Nutritional Intervention for Patients With Mild Cognitive Impairment: The Cognitive impAiRmEnt Study (CARES) Trial 1 Full Text
*Adding a blend of spices to a meal may help lower inflammation Full Text
*Nutrition and the ageing brain: Moving towards clinical applications Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Resistance Training in Middle Age Doubles Muscle NAD+ Levels Full Text
*Different Exercise Training Modalities Produce Similar Endothelial Function Improvements in Individuals With Prehypertension or Hypertension: A Randomized Clinical Trial Exercise, Endothelium and Blood Pressure Full Text
*Effects of Combined Resistance and Power Training on Cognitive Function in Older Women: A Randomized Controlled Trial Full Text
*Moderate- To High Intensity Aerobic and Resistance Exercise Reduces Peripheral Blood Regulatory Cell Populations in Older Adults With Rheumatoid Arthritis Full Text
*Multicomponent Exercise Program Reduces Frailty and Inflammatory Biomarkers and Improves Physical Performance in Community-Dwelling Older Adults: A Randomized Controlled Trial Full Text
*Walking or cycling to work associated with reduced risk of early death and illness Full Text
*Rejuvenation of Neutrophil Functions in Association With Reduced Diabetes Risk Following Ten Weeks of Low-Volume High Intensity Interval Walking in Older Adults With Prediabetes - A Pilot Study 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.
Clinical Applications of Astaxanthin in the Treatment of Ocular Diseases: Emerging Insights Full Text
Antiplatelet Activity of Astaxanthin in Control- And High Cholesterol-Fed Rats Mediated by Down-Regulation of P2Y 12, Inhibition of NF-κB, and Increasing Intracellular Levels of cAMP
Astaxanthin Improves Osteopenia Caused by Aldehyde-Stress Resulting From Aldh2 Mutation Due to Impaired Osteoblastogenesis
Astaxanthin Attenuates Hepatic Damages and Mitochondrial Dysfunction in Nonalcoholic Fatty Liver Disease by Up-Regulating the FGF21/PGC-1α Pathway

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.
*EValuation of Curcumin (Turmeric Extract) Effect on Prevention of CIN in Patient Under Elective Coronary Angiography, a Randomized Double Blind Placebocontrolled Clinical Trial Full Text
*Highly Bioavailable Curcumin Derivative Ameliorates Crohn's Disease Symptoms: A Randomized, Double-Blind, Multicenter Study
*Effect of Curcumin on Serum Urate in Asymptomatic Hyperuricemia: A Randomized Placebo-Controlled Trial
Exercise and Curcumin in Combination Improves Cognitive Function and Attenuates ER Stress in Diabetic Rats Full Text
Premature Synaptic Mitochondrial Dysfunction in the Hippocampus During Aging Contributes to Memory Loss Full Text

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.
Cardioprotective Effects of Melatonin: Focusing on Its Roles Against Diabetic Cardiomyopathy Full Text

Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250 – 500mg on days I exercise.
Nicotinamide Mononucleotide Attenuates Glucocorticoid‑induced Osteogenic Inhibition by Regulating the SIRT1/PGC‑1α Signaling Pathway Full Text
Nicotinamide Mononucleotide Administration After Sever Hypoglycemia Improves Neuronal Survival and Cognitive Function in Rats
Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons Full Text
Improving Retinal Mitochondrial Function as a Treatment for Age-Related Macular Degeneration Full Text
Reversal of Endothelial Dysfunction by Nicotinamide Mononucleotide via Extracellular Conversion to Nicotinamide Riboside Full Text

Nicotinamide Riboside (NR) – NAD+ precursor.
Increasing Ovarian NAD + Levels Improve Mitochondrial Functions and Reverse Ovarian Aging Abstract
Nicotinamide Riboside Relieves Paclitaxel-Induced Peripheral Neuropathy and Enhances Suppression of Tumor Growth in Tumor-Bearing Rats
Nicotinamide riboside-A Missing Piece in the Puzzle of Exercise Therapy for Older Adults?
Impact of Nicotinamide Riboside Supplementation on Skeletal Muscle Mitochondria and Whole-Body Glucose Homeostasis: Challenging the Current Hypothesis

Pterostilbene – found in blueberries. Anti-oxidant, anti-inflamatory and Sir1 activator. Similar to, but with greater bioavailability t han resveratrol. Taking 50mg intermittently in the same pill as resveratrol. Works better in conjunction with NAD+ precursors.
Pterostilbene Prevents LPS-induced Early Pulmonary Fibrosis by Suppressing Oxidative Stress, Inflammation and Apoptosis in Vivo

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 Promotes Osteogenesis and Alleviates Osteoporosis by Inhibiting p53 Full Text
Long-term Resveratrol Treatment Improves the Capillarization in the Skeletal Muscles of Ageing C57BL/6J Mice
Resveratrol Inhibits Particulate Matter-Induced Inflammatory Responses in Human Keratinocytes Full Text
SIRT1-dependent Mechanisms and Effects of Resveratrol for Amelioration of Muscle Wasting in NASH Mice Full Text
Resveratrol: Multi-Targets Mechanism on Neurodegenerative Diseases Based on Network Pharmacology Full Text

Other available supplements & combinations
Berberine Attenuates Cardiac Hypertrophy Through Inhibition of mTOR Signaling Pathway
Honokiol Inhibits Carotid Artery Atherosclerotic Plaque Formation by Suppressing Inflammation and Oxidative Stress Full Text
Ellagic Acid Protects Mice Against Sleep Deprivation-Induced Memory Impairment and Anxiety by Inhibiting TLR4 and Activating Nrf2 Full Text
Amelioration of Age-Related Alterations in Rat Liver: Effects of Curcumin C3 Complex, Astragalus Membranaceus and Blueberry
Protective Effect of Quercetin in Combination With Caloric Restriction Against Oxidative Stress Induced Cell Death of Saccharomyces Cerevisiae Cells
Niacin Cures Systemic NAD + Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy
Lycopene Prevents Carcinogen-Induced Cutaneous Tumor by Enhancing Activation of the Nrf2 Pathway Through p62-triggered Autophagic Keap1 Degradation Full Text
Astragaloside IV Ameliorates Radiation-Induced Senescence via Antioxidative Mechanism
Longevity-promoting Efficacies of Rutin in High Fat Diet Fed Drosophila Melanogaster
Vitamin K Status, Cardiovascular Disease, and All-Cause Mortality: A Participant-Level Meta-Analysis of 3 US Cohorts
Improving Retinal Mitochondrial Function as a Treatment for Age-Related Macular Degeneration Full Text NAC, NMN, PQQ & Rapamycin

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.
Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation Full Text
Dysregulated Expression of Monoacylglycerol Lipase Is a Marker for Anti-Diabetic Drug Metformin-Targeted Therapy to Correct Impaired Neurogenesis and Spatial Memory in Alzheimer's Disease Full Text
Metformin: Sentinel of the Epigenetic Landscapes That Underlie Cell Fate and Identity Full Text
Metformin: The Updated Protective Property in Kidney Disease Full Text
Effects of Metformin on Lifespan, Cognitive Ability and Inflammatory Response in a Short-Lived Fish

Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer.
Therapeutic Effect of Rapamycin on Aortic Dissection in Mice Full Text
Enhanced Skeletal Muscle Insulin Sensitivity After Acute Resistance-Type Exercise Is Upregulated by Rapamycin-Sensitive mTOR Complex 1 Inhibition Full Text
Longevity Genes, Cardiac Ageing, and the Pathogenesis of Cardiomyopathy: Implications for Understanding the Effects of Current and Future Treatments for Heart Failure Full Text
Prophylactic Treatment of Rapamycin Ameliorates Naturally Developing and Episode -Induced Heterotopic Ossification in Mice Expressing Human Mutant ACVR1 Full Text
Inhibition of mTOR Delayed but Could Not Prevent Experimental Collapsing Focal Segmental Glomerulosclerosis Full Text
Keap1 Governs Ageing-Induced Protein Aggregation in Endothelial Cells Full Text

Other Areas of Interest
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:
*A DNA Methylation Clock Associated With Age-Related Illnesses and Mortality Is Accelerated in Men With Combat PTSD
*Quantification of the Pace of Biological Aging in Humans Through a Blood Test, The DunedinPoAm DNA Methylation Algorithm Full Text
*Determinants of Accelerated Metabolomic and Epigenetic Aging in a UK Cohort Full Text
*Prediction of Chronological and Biological Age From Laboratory Data Full Text

Microbiome – all the little critters living in and on us have a major influence on our health and potentially our longevity.
Age-related Shifts in Gut Microbiota Contribute to Cognitive Decline in Aged Rats Full Text
Dietary Emulsifier Sodium Stearoyl Lactylate Alters Gut Microbiota in vitro and Inhibits Bacterial Butyrate Producers Full Text
Early Signs of Gut Microbiome Aging: Biomarkers of Inflammation, Metabolism, and Macromolecular Damage in Young Adulthood
*Effects of Exercise Frequency on the Gut Microbiota in Elderly Individuals Full Text
Age-related Compositional Changes and Correlations of Gut Microbiome, Serum Metabolome, and Immune Factor in Rats
*Microbiome Succession With Increasing Age in Three Oral Sites Full Text
*Faecal Microbiota Transplantation as a Home Therapy to Frail Older People Full Text
Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells

Senolytics/Senescent Cells – 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:
Identification of SYK Inhibitor, R406 as a Novel Senolytic Agent Full Text
Eliminating Senescent Chondrogenic Progenitor Cells Enhances Chondrogenesis Under Intermittent Hydrostatic Pressure for the Treatment of OA Full Text
Platelet Activation Is Triggered by Factors Secreted by Senescent Endothelial HMEC-1 Cells In Vitro Full Text
Defined p16 High Senescent Cell Types Are Indispensable for Mouse Healthspan Abstract
Senescent Cells in Cancer Therapy: Friends or Foes? Full Text

Stem Cells & Exosomes (small packets of information released by cells)
*Cell Therapy Promising Against Angina From Microvascular Dysfunction
*Cell Therapy Shows Promise in Parkinson’s
Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration Full Text
Identifying the Therapeutic Significance of Mesenchymal Stem Cells Full Text
Extracellular Vesicles From Human Urine-Derived Stem Cells Inhibit Glucocorticoid-Induced Osteonecrosis of the Femoral Head by Transporting and Releasing Pro-Angiogenic DMBT1 and Anti-Apoptotic TIMP1

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:
Growth Differentiation factor-11 Supplementation Improves Survival and Promotes Recovery After Ischemic Stroke in Aged Mice Full Text
Plasma Proteomic Profiling of Young and Old Mice Reveals cadherin-13 Prevents Age-Related Bone Loss Full Text
[size=4][font=arial][url="https://pubmed.ncbi.nlm.nih.gov/32384696/"][color=rgb(17,85,204)][background=transparent]Infusion of P