March 2021 Longevity Review

Hello and welcome again to this month’s longevity review. There was plenty of good news this month with a new compound showing efficacy in humans and the first inklings as to the best time of day to take your supplements, but also a disappointing result with regards to Nicotinamide Riboside. However, even disappointing results increase our understanding so shouldn’t be seen in a negative light.

The big news from me is that I have finished my teaching contract and because of COVID I don’t have another one for the time being. This is great news as I will finally be able to devote most of my time towards longevity advocacy and in particular the launching of a federally incorporated non-profit: The Canadian Longevity Association. Unlike other countries, Canada does not have an organisation dedicated to advancing our longevity agenda and this needs to change!

The association will focus on four areas:

• Public: Increase public awareness and support for longevity research & treatments.
• Scientific: Encourage and support Canadian researchers, improve their funding and foster connections & collaborations, as well as publicising their results.
• Commercial: Support Canadian biotech, increase private investment in this area and facilitate the commercialisation of longevity research.
• Governmental: Influence and help shape government policy and increase government funding for longevity research.

This is something I cannot do on my own and I've started assembling a group of volunteers - however, we need more. If you have an interest in making a difference and helping the defeat of ageing, then you have found the right place. No matter what your skill set is or how much time you have to spare, we can use your help.

I understand that not everyone has the time, energy or inclination to volunteer, but please get in touch to receive updates and at least join the association once we launch.

We can be reached at:

canadianlongevity@gmail.com or contact@canadianlongevity.ca

A reminder that I have set up a Patreon account at the behest of a reader. Anyone wishing to buy me a cup of coffee is greatly appreciated! As an extra bonus, every month I’ll send you a PDF of all the studies which didn’t quite make the cut for this newsletter. There are still a lot of gems to be found! You can see a free example on Patreon.
Stay safe!

Follow me on Twitter @ChrisPollyanna1 for the latest updates, and also please join my longevity Facebook group.

*Once again this newsletter has been cut short due to size restrictions - to see news on stem cells & others, see the full PDF version at Patreon or Here.*
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Round-Up:

This compound (Glycine & N-acetylcysteine), was new to me, however, this study showed some impressive results in improving cognitive & physical health as well as targeting 4 of the 9 Hallmarks of Aging. Even more impressively, this was a study in humans, albeit only 8 subjects. Definitely keeping my eyes peeled for the follow up studies with more participants.
*GlyNAC improves multiple defects in aging to boost strength and cognition in older humans Full Text

In more disappointing news, the latest results from the Interventions Testing Program showed that the popular NAD+ boosting supplement Nicotinamide Riboside (NR) failed to extend mouse lifespan. However, if you’re male, there was further encouraging news about 17-a-estradiol, which in this follow-up study, also increased male lifespan when started late in life - joining Rapamycin with that distinction.
17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex Full Text

This interesting study, although only a simulation, looked at the timing of supplement intake with their effectiveness. This is something I’ve long wondered about - at what time should I take my numerous supplements and does it matter? Here, Nicotinamide Mononucleotide (NMN) & Resveratrol were looked at.
Time of day boosts effectiveness of anti-aging supplements
Aging affects circadian clock and metabolism and modulates timing of medication Full Text

This study showed the power of exosomes/extracellular vesicles (packets of chemical information) released by young stem cells. Instead of transplanting stem cells, the beneficial products secreted by them could be administered instead, which could make treatment easier. This is an exciting area of research.
MSC Extracellular Vesicles Reduce Mouse Senescence Full Text

Finishing with a couple of papers which used different gene editing/therapy methods to counteract hearing loss. Hear! Hear! I say!
VEGF-A165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss Full Text
Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing Full Text

Covid-19 Longevity Related Papers:
*The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with COVID-19: a randomized clinical trial Full Text
*Severe vitamin D deficiency is not related to SARS-CoV-2 infection but may increase mortality risk in hospitalized adults: a retrospective case-control study in an Arab Gulf country Full Text
*Effects of metformin, insulin on COVID-19 patients with pre-existed type 2 diabetes: A multicentral retrospective study Full Text
Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections Full Text
SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: beneficial effects of melatonin Full Text

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Videos to watch:

I want to point out a couple of YouTube channels which are worth checking out. I’ve only watched a few of the videos, but they have been good, with lots of interviews with leading longevity researchers.

Modern Healthspan

Healthy Longevity Webinar Series

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2021 Supplemental Information

**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
*Fasting can be an effective way to start a diet Full text
Calorie restriction prevents age-related changes in the intestinal microbiota Full Text
Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner Full Text

Diet
*Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview Full Text
*Consumption of chilies and sweet peppers is associated with lower risk of sarcopenia in older adults Full Text
*Dietary patterns and associations with biomarkers of inflammation in adults: a systematic review of observational studies Full Text

Exercise
*Association between physical activity and cardiovascular risk factors: Dose and sex matter Full Text
*Fitness, Fatness, and Mortality in Men and Women From the UK Biobank: Prospective Cohort Study Full Text
*The association between activity levels and skin moisturising function in adults 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
Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1 Full Text
Effect of dietary astaxanthin administration on the growth performance and innate immunity of juvenile crucian carp ( Carassius auratus)
Z-Isomers of Astaxanthin Exhibit Greater Bioavailability and Tissue Accumulation Efficiency than the All- E-Isomer

Curcumin
*The effects of nano-curcumin supplementation on Th2/tregulatory axis in migraine patients: a randomized, double-blind, placebo-controlled trial
Protective effects of curcumin against rat intestinal inflammation‑related motility disorders Full Text
Therapeutic effects of EGF-modified curcumin/chitosan nano-spray on wound healing Full Text

Fisetin
Neuroprotective potential of fisetin in an experimental model of spinal cord injury: via modulation of NF-κB/IκBα pathway Full Text
Fisetin Attenuates Myocardial Ischemia-Reperfusion Injury by Activating the Reperfusion Injury Salvage Kinase (RISK) Signaling Pathway Full Text
Fisetin attenuates periodontitis through FGFR1/TLR4/NLRP3 inflammasome pathway

Melatonin
*Consumption of melatonin supplement improves cardiovascular disease risk factors and anthropometric indices in type 2 diabetes mellitus patients: a double-blind, randomized, placebo-controlled trial Full Text
*Effects of melatonin supplementation on disease activity, oxidative stress, inflammatory, and metabolic parameters in patients with rheumatoid arthritis: a randomized double-blind placebo-controlled trial
*Melatonin mitigates disrupted circadian rhythms, lowers intraocular pressure and improves retinal ganglion cells function in glaucoma

Nicotinamide MonoNucleotide (NMN)
Reduced Nicotinamide Mononucleotide Is a New NAD+ Precursor Full Text
Nicotinamide mononucleotide attenuates isoproterenol-induced cardiac fibrosis by regulating oxidative stress and Smad3 acetylation
Nicotinamide mononucleotide prevents cisplatin-induced cognitive impairments

Nicotinamide Riboside (NR)
SIRT3 is required for liver regeneration but not for the beneficial effect of nicotinamide riboside Full Text
NAD+ Eases Symptoms of a Premature Aging Disease in Mice Full Text
Of mice and men: opposing effects of nicotinamide riboside on skeletal muscle physiology at rest and during exercise Full Text

Pterostilbene
Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells Full Text
Pterostilbene Improves Stress-Related Behaviors and Partially Reverses Underlying Neuroinflammatory and Hormonal Changes in Stress-Challenged Mice
Pterostilbene Ameliorates DSS-Induced Intestinal Epithelial Barrier Loss in Mice via Suppression of the NF-κB-Mediated MLCK-MLC Signaling Pathway

Resveratrol
*Distribution and metabolism of [14C]-resveratrol in human prostate tissue after oral administration of a "dietary-achievable" or "pharmacological" dose: what are the implications for anticancer activity? Full Text
Anti-inflammatory effect of resveratrol attenuates the severity of diabetic neuropathy by activating the Nrf2 pathway Full Text
Preconceptional Resveratrol Supplementation Partially Counteracts Age-Related Reproductive Complications in C57BL/6J Female Mice Full Text

Spermidine
Spermidine supplementation in rare translation-associated disorders Full Text

Other available supplements (in alphabetical order) & combinations
NMR-Based Metabolomic Analysis for the Effects of α-Ketoglutarate Supplementation on C2C12 Myoblasts in Different Energy States Full Text
*Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Elderly Body Composition and Muscle Strength: A Review of Clinical Trials Full Text
*Effect of six weeks 1000 mg/day vitamin C supplementation and healthy training in elderly women on genes expression associated with the immune response - a randomized controlled trial Full Text
*The Therapeutic Potential of Carnosine/Anserine Supplementation against Cognitive Decline: A Systematic Review with Meta-Analysis Full Text
*Beneficial effect of Chlorella pyrenoidosa drink on healthy subjects: A randomized, placebo-controlled, double-blind, cross-over clinical trial
*Creatine Supplementation in Women's Health: A Lifespan Perspective Full Text
*Vitamin D Supplementation and Impact on Skeletal Muscle Function in Cell and Animal Models and an Aging Population: What Do We Know So Far? Full Text
*Randomized, crossover clinical efficacy trial in humans and mice on tear secretion promotion and lacrimal gland protection by molecular hydrogen Full Text
*L-Glutamine Supplementation Enhances Strength and Power of Knee Muscles and Improves Glycemia Control and Plasma Redox Balance in Exercising Elderly Women Full Text
*Effects of n-3 EPA and DHA supplementation on fat free mass and physical performance in elderly. A systematic review and meta-analysis of randomized clinical trial Full Text
Selenium Supplements Protect Against Obesity in Mice Full Text

Prescription Supplements
Metformin
*Metformin and health outcomes: An umbrella review of systematic reviews with meta-analyses Full Text
*Metformin use in cancer survivors with diabetes reduces all-cause mortality, based on the Korean National Health Insurance Service between 2002 and 2015 Full Text
*The Association Between Metformin Treatment and Outcomes in Type 2 Diabetes Mellitus Patients With Heart Failure With Preserved Ejection Fraction: A Retrospective Study Full Text

Rapamycin (sirolimus)
*A positive feedback loop between mTORC1 and cathelicidin promotes skin inflammation in rosacea Full Text
Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension Full Text
Reducing lipofuscin accumulation and cardiomyocytic senescence of aging heart by enhancing autophagy

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Binary Clock Predicts Biological Age Full Text
*Male-specific age estimation based on Y-chromosomal DNA methylation Full Text
*Comparison of DNA methylation clocks in black South African men Full Text

Bonus Aging Clock Weight Loss Studies
*Weight management intervention identifies association of decreased DNA methylation age with improved functional age measures in older adults with obesity Full Text
*Lifestyle weight-loss intervention may attenuate methylation aging: the CENTRAL MRI randomized controlled trial Full Text

Blood Factors
*Experimental treatment offers hope of fertility for early menopausal women Abstract
*Healthy dietary patterns are associated with lower concentrations of growth differentiation factor 15 in older adults Full Text
Plasma from healthy donors protects blood-brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia Full Text

Epigenetics & Cellular Reprogramming
Epigenetic alterations in stem cell ageing-a promising target for age-reversing interventions? Full Text
*A Meta-Analysis of Brain DNA Methylation Across Sex, Age, and Alzheimer's Disease Points for Accelerated Epigenetic Aging in Neurodegeneration Full Text
*Sperm DNA Methylation at Metabolism-Related Genes in Vegan Subjects Full Text

Exosomes (small packets of information released by cells)
Exosomes derived from human placental mesenchymal stem cells enhanced the recovery of spinal cord injury by activating endogenous neurogenesis Full Text
Extracellular Vesicles for the Treatment of Radiation-Induced Normal Tissue Toxicity in the Lung Full Text
Human placenta mesenchymal stem cell-derived exosomes delay H 2 O 2-induced aging in mouse cholangioids Full Text

Genetics including CRISPR
*Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals Full Text
*Lifespan extension conferred by mitogen-activated protein kinase kinase kinase 5 ( MAP3K5) longevity-associated gene variation is confined to at-risk men with a cardiometabolic disease Full Text
Characterization of an active LINE-1 in the naked mole-rat genome Full Text

Lifespan Lengthening Interventions
Cap-independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17α-estradiol Full Text
Hydrogen sulfide treatment at the late growth stage of Saccharomyces cerevisiae extends
chronological lifespan Full Text
Host-commensal interaction promotes health and lifespan in Caenorhabditis elegans through the activation of HLH-30/TFEB-mediated autophagy Full Text
Kaempferia parviflora Rhizome Extract Inhibits Glutamate-Induced Toxicity in HT-22 Mouse Hippocampal Neuronal Cells and Extends Longevity in Caenorhabditis elegans Full Text
Increased Stress Resistance and Lifespan in Chaenorhabditis elegans Wildtype and Knockout Mutants-Implications for Depression Treatment by Medicinal Herbs Full Text

Microbiome
Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites Full Text
Young at Gut-Turning Back the Clock with the Gut Microbiome Full Text
Longitudinal Multi-omics and Microbiome Meta-analysis Identify an Asymptomatic Gingival State That Links Gingivitis, Periodontitis, and Aging Full Text

Miscellaneous Molecules
17β-Estradiol alleviates cardiac aging induced by D-galactose by downregulating the methylation of autophagy-related genes
*Long Term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality Full Text
Elamipretide (SS-31) Improves Functional Connectivity in Hippocampus and Other Related Regions Following Prolonged Neuroinflammation Induced by Lipopolysaccharide in Aged Rats Full Text
Hydrogen Sulfide Restored the Diurnal Variation in Cardiac Function of Aging Mice Full Text
Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice Full Text

Opinion/Editorials/Theory
*Demographic perspectives on the rise of longevity Full Text
Fetal origins-A life cycle model of health and aging from conception to death Full Text
Divergent Aging of Isogenic Yeast Cells Revealed through Single-Cell Phenotypic Dynamics Full Text

Reviews
Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging Full Text
Cancer and Aging: Two Tightly Interconnected Biological Processes Full Text
Viruses and Endogenous Retroviruses as Roots for Neuroinflammation and Neurodegenerative Diseases Full Text

Senolytics/Senescent Cells
[size=4][font=arial][url="https://pubmed.ncbi.nlm.nih.gov/33649045/"][color=rgb(17,85,204)]Senolytic elimination of Cox2-expressing senescent cells inhibits the growth of premalignant pancreatic lesions[/color