January 2021 Longevity Review

Now that 2020 is firmly in the rearview mirror and the light at the end of the COVID tunnel is becoming brighter, longevity science becomes less of a distraction and more of an enticement towards better times. Examples of this include hope for progeria sufferers using gene therapy, a new method to discover drug combinations and yet more pre-clinical evidence for senolytics.

Closer to home, I want to mention a new supplement I have just ordered for my parents which is one of the first to have been formulated with the Hallmarks of Aging (2013 paper) in mind. Although there are no clinical studies to back it up, I am in agreement with most of the ingredients and I respect the scientists on their advisory board. It’s pricey, but could be cheaper than ordering the 12 ingredients separately. Full disclosure: the charity I volunteer for, LEAF/Lifespan.io, stands to benefit from sales as NOVOS is a public benefit company.

I also want to introduce a relatively new website by a reader of this newsletter. Longevity Marketcap and its attendant newsletter is for those of you interested in investing in this field. (Aubrey de Grey has signed up!) If I had spare money that I could risk losing, then I would certainly support these fledgling companies.

Lastly, I want to point out 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 quite a few gems to be found! You can see a free example on Patreon.
Stay safe!
Follow me on Twitter @ChrisPollyanna1 for the latest updates.
Once again I have run up against the blog length limit on LongeCity - the full newsletter can be found on the Toronto Longevity Association Facebook Group or my Patreon page.
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January Round-Up:
Although it is debatable how relevant progeria is to normal ageing, it is still heartening to see any progress for this terrible affliction. And, it is even better when median lifespan can be more than doubled using genetic base editing in living mice. With luck, these exciting results will quickly move to clinical trials.
Groundbreaking New Therapy for Progeria ‘Incredible’ gene-editing result - Science Review
Nature Review Abstract

I have long gone on about how the only way we are going to achieve longevity is through a combinational approach. In this paper, researchers have used a deep-neural network to find drug pairs with enhanced anti-aging effects.
Identification of drug combinations on the basis of machine learning to maximize anti-aging effects Full Text

Alpha-Ketogluterate has increasingly been on my radar for the past year or so, and this study further demonstrates why. In previous studies it increased the healthspan of mice, so delaying age-related fertility decline fits in with that narrative.
Alpha-Ketoglutarate Delays Age‐Related Fertility Decline Full Text

Senolytics, the clearance of senescent cells, has long featured in this round-up section, and here is the latest indication of its potential. Still in mice, but using a drug combination already used by self-experimenters - cognitive impairment was the target this time.
Senolytics Alleviate Age‐Related Cognitive Decline Full Text

Nature Aging has finally launched, which marks an important milestone in the acceptance of longevity science in the broader scientific community. The first issue contains a thorough review of fasting, which until the advent of effective rejuvenation therapies, remains one of the best longevity treatments available (and certainly the cheapest!).
*Intermittent and periodic fasting, longevity and disease Full Text

Covid-19 Longevity Related Papers:
*Oral nano-curcumin formulation efficacy in management of mild to moderate hospitalized coronavirus disease-19 patients: An open label nonrandomized clinical trial Full Text
Metformin use reduces risk of death for patients with COVID-19 and diabetes Full Text
Investigating the Link Between COVID-19 and Telomeres
Study links severe COVID-19 disease to short telomeres Full text
Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths-Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action Full Text

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Videos to watch:
A couple short positive longevity videos from the BBC & Bloomberg news sites, demonstrating how this field is becoming mainstream, which can only be a good thing.
BBC - Can science reverse the ageing process?
Bloomberg - Meet The Scientists Trying to Reverse Aging
Bonus video - from LEAF’s Journal Club, Irina Conboy talks us through her latest research:
Plasma Dilution Rejuvenates Cognition and Reduces Neuroinflammation
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Supplemental Information

Lifestyle
Fasting/Dietary Restriction
*Association between Time Restricted Feeding and Cognitive Status in Older Italian Adults Full Text
Effects of Late-Life Caloric Restriction on Age-Related Alterations in the Rat Cortex and Hippocampus Full Text

Diet
*Green Mediterranean diet cuts non-alcoholic fatty liver disease by half Full text
*Dietary strawberry improves cognition in a randomized, double-blind, placebo-controlled trial in older adults Full Text
*Astaxanthin-, β-Carotene-, and Resveratrol-Rich Foods Support Resistance Training-Induced Adaptation Full Text

Exercise
*No limit to cardiovascular benefits of exercise, study finds Full Text
*Stretching is Superior to Brisk Walking for Reducing Blood Pressure in People With High–Normal Blood Pressure or Stage I Hypertension Full Text
*High-intensity interval training and essential amino acid supplementation: Effects on muscle characteristics and whole-body protein turnover Full Text

Non-prescription Supplements (in alphabetical order)
Astaxanthin
**The antioxidant and anti-inflammatory effects of astaxanthin supplementation on the expression of miR-146a and miR-126 in patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled clinical trial
Astaxanthin attenuates alcoholic cardiomyopathy via inhibition of endoplasmic reticulum stress-mediated cardiac apoptosis Full Text
Astaxanthin Prevents Atrophy in Slow Muscle Fibers by Inhibiting Mitochondrial Reactive Oxygen Species via a Mitochondria-Mediated Apoptosis Pathway Full Text

Curcumin
*Potential Therapeutic Effects of Curcumin on Glycemic and Lipid Profile in Uncomplicated Type 2 Diabetes-A Meta-Analysis of Randomized Controlled Trial Full Text
*Efficacy of a curcumin extract (Curcugen™) on gastrointestinal symptoms and intestinal microbiota in adults with self-reported digestive complaints: a randomised, double-blind, placebo-controlled study Full Text
*Therapeutic effects of turmeric or curcumin extract on pain and function for individuals with knee osteoarthritis: a systematic review 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 protects against high fat diet-induced nephropathy by inhibiting inflammation and oxidative stress via the blockage of iRhom2/NF-κB signaling

Melatonin
*Melatonin may slow disease progression in amyotrophic lateral sclerosis: Findings from the Pooled Resource Open-Access ALS Clinic Trials database
*Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials
Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases Full Text

Nicotinamide MonoNucleotide (NMN)
Generation and assessment of high-quality mouse oocytes and embryos following nicotinamide mononucleotide administration Full Text

Nicotinamide Riboside (NR)
*Co-therapy with S-adenosylmethionine and nicotinamide riboside improves t-cell survival and function in Arts Syndrome (PRPS1 deficiency) Full Text
*Nicotinamide riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise
NAD+ can restore age-related muscle deterioration, research finds Full Text

Pterostilbene
Analysis of Lipid Peroxidation by UPLC-MS/MS and Retinoprotective Effects of the Natural Polyphenol Pterostilbene Full Text
Pterostilbene influences glycemia and lipidemia and enhances antioxidant status in the liver of rats that consumed sucrose solution

Resveratrol
*Hypoglycemic Effect of Resveratrol: A Systematic Review and Meta-Analysis Full Text
*Resveratrol-induced remodelling of myocellular lipid stores: A study in metabolically compromised humans Full Text
Oral administration of resveratrol or lactic acid bacterium improves lens elasticity Full Text

Spermidine
Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length Full Text
Spermidine and Rapamycin Reveal Distinct Autophagy Flux Response and Cargo Receptor Clearance Profile Full Text
Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca 2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS Full Text

Other available supplements & natural substances (in alphabetical order)
*Does aspirin lower colorectal cancer risk in older adults? It depends on when they start. Abstract
*Increasing skeletal muscle carnitine content in older individuals increases whole-body fat oxidation during moderate-intensity exercise Full Text
Dietary chlorogenic acid ameliorates oxidative stress and improves endothelial function in diabetic mice via Nrf2 activation Full Text
Dietary administration of cumin-derived cuminaldehyde induce neuroprotective and learning and memory enhancement effects to aging mice Full Text
(-)-Gallocatechin gallate from green tea rescues cognitive impairment through restoring hippocampal silent synapses in post-menopausal depression Full Text
The antioxidant activities of Korean Red Ginseng ( Panax ginseng) and ginsenosides: A systemic review through in vivo and clinical trials Full Text
Glucosamine May Be a Caloric Restriction Mimetic Abstract
Lack of Autophagy Induction by Lithium Decreases Neuroprotective Effects in the Striatum of Aged Rats Full Text
Rosmarinic acid suppresses tau phosphorylation and cognitive decline by downregulating the JNK signaling pathway Full Text

Combinations & Reviews
Aging and age-related diseases: from mechanisms to therapeutic strategies Full Text
Effects of melatonin and resveratrol on recognition memory and passive avoidance performance in a mouse model of Alzheimer's disease Full Text
Beneficial Effects of Epigallocatechin-3- O-Gallate, Chlorogenic Acid, Resveratrol, and Curcumin on Neurodegenerative Diseases Full Text
The Beneficial Effects of Principal Polyphenols from Green Tea, Coffee, Wine, and Curry on Obesity Full Text
Modulation of Autophagy in Cancer Cells by Dietary Polyphenols Full Text
A bioavailable form of curcumin, in combination with vitamin-D- and omega-3-enriched diet, modifies disease onset and outcomes in a murine model of collagen-induced arthritis Full Text

Prescription Supplements
Metformin
*Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms Full Text
Effect of Metformin on Cardiac Metabolism and Longevity in Aged Female Mice Full Text
Metformin treatment in late middle age improves cognitive function with alleviation of microglial activation and enhancement of autophagy in the hippocampus Full Text

Rapamycin (sirolimus)
Rapamycin is Not a Caloric Restriction Mimetic Full Text
Rapamycin relieves the cataract caused by ablation of Gja8b through stimulating autophagy in zebrafish Full Text
Adiponectin receptor 1 variants contribute to hypertrophic cardiomyopathy that can be reversed by rapamycin Full Text

Other Areas of Interest (in alphabetical order)
Ageing Clocks & other biomarkers of ageing
*Associations of Age, Sex, Race/Ethnicity and Education with 13 Epigenetic Clocks in a Nationally Representative US Sample: The Health and Retirement Study Full Text
*Characteristics of Epigenetic Clocks Across Blood and Brain Tissue in Older Women and Men Full Text

Epigenetics & Cellular Reprogramming
Epigenetics of Aging and Aging-Associated Diseases Full Text
Paternal age affects offspring via an epigenetic mechanism involving REST/NRSF Full Text
Epigenetic Modifications Induced by Olive Oil and Its Phenolic Compounds: A Systematic Review Full Text

Exosomes (small packets of information released by cells)
Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis Full Text
Human umbilical cord mesenchymal stem cell-derived extracellular vesicles ameliorate airway inflammation in a rat model of chronic obstructive pulmonary disease (COPD) Full Text
Human umbilical cord mesenchymal stem cell-derived exosomal miR-146a-5p reduces microglial-mediated neuroinflammation via suppression of the IRAK1/TRAF6 signaling pathway after ischemic stroke Full Text

Genes & Proteins
*Protein signatures of centenarians and their offspring suggest centenarians age slower than other humans Full Text
*The association of APOE ε4 with cognitive function over the adult life course and incidence of dementia: 20 years follow-up of the Whitehall II study Full Tex
*Exome-wide association study identifies FN3KRP and PGP as new candidate longevity genes Full Text

Lifespan Lengthening Interventions
Age-related Decline in Cellular Stress Response Alleviated Full Text
A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence Abstract
Sulforaphane promotes C. elegans longevity and healthspan via DAF-16/DAF-2 insulin/IGF-1 signaling Full Text
Background radiation impacts human longevity and cancer mortality: reconsidering the linear no-threshold paradigm
Extracts of the Tiger Milk Mushroom ( Lignosus rhinocerus) Enhance Stress Resistance and Extend Lifespan in Caenorhabditis elegans via the DAF-16/FoxO Signaling Pathway Full Text
A dietary sterol trade-off determines lifespan responses to dietary restriction in Drosophila melanogaster females Full Text
Therapeutic potential of bioactive compounds from Punica granatum extracts against aging and complicity of FOXO orthologue DAF-16 in Caenorhabditis elegans Full Text
Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases Full Text
Evaluation of the geroprotective effects of withaferin A in Drosophila melanogaster Full Text

Microbiome
Gerobiotics: probiotics targeting fundamental aging processes Full Text
Improvement of gastrointestinal discomfort and inflammatory status by a synbiotic in middle-aged adults: a double-blind randomized placebo-controlled trial Full Text
Gut microbiota as the key controllers of "healthy" aging of elderly people Full Text

Miscellaneous Molecules
Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice Full Text
Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response Full Text
Intraperitoneal injection of Desferal® alleviated the age-related bone loss and senescence of bone marrow stromal cells in rats Full Text
Fluoxetine Promotes Hippocampal Oligodendrocyte Maturation and Delays Learning and Memory Decline in APP/PS1 Mice Full Text
FTY720 Prevents Spatial Memory Impairment in a Rat Model of Chronic Cerebral Hypoperfusion via a SIRT3-Independent Pathway Full Text
ILB® resolves inflammatory scarring and promotes functional tissue repair full text
Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice Full Text
See how they run: 'Exercise protein' doubles running capacity, restores function and extends healthy lifespans in older mice Full Text
Klotho retards renal fibrosis through targeting mitochondrial dysfunction and cellular senescence in renal tubular cells Full Text
Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease Full Text
*Long-term testosterone therapy improves liver parameters and steatosis in hypogonadal men: a prospective controlled registry study

Observational Studies
*When your brain looks older than expected: combined lifestyle risk and BrainAGE Full Text
*Brain health across the entire glycaemic spectrum: the UK Biobank Full Text
*Long-term exposure to ambient air pollution and risk of dementia: Results of the prospective Three-City Study Full Text

Reviews
Principles of the Molecular and Cellular Mechanisms of Aging Full Text
Mono(ADP-ribosyl)ation Enzymes and NAD + Metabolism: A Focus on Diseases and Therapeutic Perspectives Full Text
DNA damage-how and why we age? Full Text

Senescent Cells & Senolytics
Senolytic combination of Dasatinib and Quercetin alleviates intestinal senescence and inflammation and modulates the gut microbiome in aged mice
Targeting and clearance of senescent foamy macrophages and senescent endothelial cells by antibody-functionalized mesoporous silica nanoparticles for alleviating aorta atherosclerosis Full Text
Anti-senescent drug screening by deep learning-based morphology senescence scoring Full Text

Stem Cells
[size=4][font=arial][url="https://pubmed.ncbi.nlm.nih.gov/33382341/"][color=rgb(17,85,204)][background=transparent]Rejuvenated ageing mesenchymal stem cells by stepwise prec