July 2022 Longevity Review

As the dog days of summer are upon us, and productivity takes a nosedive in the sweltering heat (OK, maybe that’s just me!), it appears that there has been a spillover effect in the longevity field with not many exciting breakthroughs to choose from for the Round Up. However, having said that, there were of course still plenty of interesting results. Apart from the usual senolytic papers once again showing the potential of our old friends D & Q, there are a trio of supplements which help with ovarian ageing in the reproductive health section, and in the expanded review section there are a couple extra general reviews on whether the ageing process can be slowed down (spoiler alert - it can!) - plus much more!

CLA News

Between catching and recovering from covid and not having a/c in the summer heat, July was not my most productive month, unless researching this newsletter & starting to learn how to use Wordpress counts? Hopefully, we will now be making progress on the new Wordpress site.

Canadian Longevity Association

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Canadian Longevity Spotlight

Rapamycin News

If you are at all interested in taking Rapamycin, the longevity drug closest to prime time and which I will start taking later this month, another Canadian living down south in California has set up a website dedicated to it. Rapamycin News provides not only news and info about Rapamycin, but also information on how to get hold of it and forums for users to share their experiences and ask questions.

July 2022 Round-Up:

Mitochondria are the power sources for all of our cells, and also one of the main causes of ageing once they start to become dysfunctional. Here, mitochondria from young mice were transfused into older mice which improved their hippocampal and cortical tissue mitochondrial function. According to a press release from the company behind the research, this was just the first in a series of papers looking at different parts of the body - it will be interesting to see what these future papers hold.
Bioreactor-Grown Mitochondria for Potential Anti-Aging Press Release Full Text

Although stem cells have been in use for some time now, the results have been inconsistent and any beneficial effects mainly due to the signalling molecules they release. They will reach their true potential once we can engineer them to release the specific molecules we desire. This example piqued my interest because the researchers did just that for at least one of the signalling molecules to improve cognition in mice.
MicroRNA-206 down-regulated human umbilical cord mesenchymal stem cells alleviate cognitive decline in D-galactose-induced aging mice Full Text

It has taken a long time for gene therapy to hit the mainstream, but it finally is beginning to. Here’s a report of a new therapy for an age-related condition which highlights its potential.
*Gene Therapy Shows Promise for Age-Related Macular Degeneration

Ending on something a little bit different, researchers have developed a wearable ultrasound patch that can deliver continuous monitoring of the internal organs and tissues for up to 48 hours. Although not a direct longevity intervention, anything that can improve the monitoring of our health has to be beneficial.
*Engineers develop stickers that can see inside the body Abstract

Supplemental Section

Lifestyle
*Exercise and Healthy Diet Cannot Replace Each Other Abstract
*Analyzing Successful Aging and Longevity: Risk Factors and Health Promoters in 2020 Older Adults Full Text

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.
*Study finds people who practice intermittent fasting experience less severe complications from COVID-19 Full Text
*Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis Full Text
Life-long dietary restrictions have negligible or damaging effects on late-life cognitive performance: A key role for genetics in outcomes Full Text

Diet – let food be thy medicine…
*Dietary regulation in health and disease Full Text
*Eating more ultra-processed foods associated with increased risk of dementia Abstract
Effects of Ketogenic Diet on Neuroinflammation in Neurodegenerative Diseases Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Resistance Circuit Training or Walking Training: Which Program Improves Muscle Strength and Functional Autonomy More in Older Women? Full Text
*Using wearables to promote physical activity in old age Full Text
*Potential harms of supplementation with high doses of antioxidants in athletes Full Text (June 2022)

Non-prescription Supplements (in alphabetical order)

NOTE - the supplements selected below are not exhaustive. They reflect what I thought were the most interesting ones back in 2019, with only a few updates since. I do individual searches for each and simply do not have time to do all others. Additionally, I’ve noticed how a lot of natural supplements affect the same genetic pathways, so I think that there is a lot of overlap and redundancy.

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotenoid, it has anti-oxidative, anti-inflammatory, anti-cancer, neuro-protective and skin-protective qualities.
Pharmaceutical and nutraceutical potential of natural bioactive pigment: astaxanthin Full Text
Mechanism of Hyperbaric Oxygen Combined with Astaxanthin Mediating Keap1/Nrf2/HO-1 Pathway to Improve Exercise Fatigue in Mice Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
*Effect of curcumin supplementation on exercise-induced muscle damage: a narrative review Full Text
*Reconnoitering the Therapeutic Role of Curcumin in Disease Prevention and Treatment: Lessons Learnt and Future Directions Full Text
*A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health Full Text

Melatonin – a natural hormone produced in the pineal gland, it helps us fall asleep every night, but it has many other functions, including as a mitochondrial antioxidant.
Melatonin treatment improves cognitive deficits by altering inflammatory and neurotrophic factors in the hippocampus of obese mice
Prolonged administration of melatonin ameliorates liver phenotypes in cholestatic murine model Full Text
Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα‐dependent pathway Full Text

Nicotinamide MonoNucleotide (NMN)
NAD+ Helps Natural Killer Cells to Fight Cancer Abstract
Nicotinamide Mononucleotide Ameliorates Cellular Senescence and Inflammation Caused by Sodium Iodate in RPE Full Text
Nicotinamide Mononucleotide and Coenzyme Q10 Protects Fibroblast Senescence Induced by Particulate Matter Preconditioned Mast Cells Full Text

Nicotinamide Riboside (NR)
Nicotinamide Riboside and Dihydronicotinic Acid Riboside Synergistically Increase Intracellular NAD+ by Generating Dihydronicotinamide Riboside Full Text
NAD+ Precursors: A Questionable Redundancy Full Text & NMN

Pterostilbene
JAK2/STAT3 pathway mediates beneficial effects of pterostilbene on cardiac contractile and electrical function in the setting of myocardial reperfusion injury

Resveratrol
*Anti-inflammatory effects of resveratrol in patients with cardiovascular disease: A systematic review and meta-analysis of randomized controlled trials Full Text
*Resveratrol supplementation efficiently improves endothelial health: A systematic review and meta-analysis of randomized controlled trials
Disease-Associated Regulation of Non-Coding RNAs by Resveratrol: Molecular Insights and Therapeutic Applications Full Text

Spermidine
Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model Full Text
Research Progress and Potential Applications of Spermidine in Ocular Diseases Full Text
Polyamines and Their Metabolism: From the Maintenance of Physiological Homeostasis to the Mediation of Disease Full Text

Other available supplements (in alphabetical order)
*Vitamin B6 supplements could reduce anxiety and depression Full Text
An umbrella review of systematic reviews of β-hydroxy-β-methyl butyrate supplementation in ageing and clinical practice Full Text
*Catechin-Rich Green Tea Extract Reduced Intestinal Inflammation and Fasting Glucose in Metabolic Syndrome and Healthy Adults: A Randomized, Controlled, Crossover Trial Full Text
*Vitamin D Supplements May Make Alzheimer’s Worse Full Text
*Krill oil improved osteoarthritic knee pain in adults with mild to moderate knee osteoarthritis: a 6-month multicenter, randomized, double-blind, placebo-controlled trial Full Text
*Randomised Controlled Trial of Fish Oil Supplementation on Responsiveness to Resistance Exercise Training in Sarcopenic Older Women Full Text
*Targeted Plasmalogen Supplementation: Effects on Blood Plasmalogens, Oxidative Stress Biomarkers, Cognition, and Mobility in Cognitively Impaired Persons Full Text
*Effects of Quercetin Glycoside Supplementation Combined With Low-Intensity Resistance Training on Muscle Quantity and Stiffness: A Randomized, Controlled Trial Full Text
Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis Full Text

Combinations of Supplements
Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress Full Text
Sphingolipids and DHA Improve Cognitive Deficits in Aged Beagle Dogs Full Text
Dietary Supplement Containing Micronutrients, Phosphatidylserine, and Docosahexaenoic Acid Counteracts Cognitive Impairment in D-Galactose-Induced Aged Rats Full Text

Prescription Supplements

Metformin
Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease Full Text
Therapeutic vs. Suprapharmacological Metformin Concentrations: Different Effects on Energy Metabolism and Mitochondrial Function in Skeletal Muscle Cells in vitro Full Text
*Metformin treatment is associated with improved outcome in patients with diabetes and advanced heart failure (HFrEF) Full Text

Rapamycin (sirolimus)
Transient rapamycin treatment during developmental stage extends lifespan in Mus musculus and Drosophila melanogaster Full Text
*The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review Full Text

Miscellaneous Molecules
*Acetyl-cholinesterase-inhibitors slow cognitive decline and decrease overall mortality in older patients with dementia Full Text
Investigational drug fosters nerve repair after injury Full Text
Ranolazine Counteracts Strength Impairment and Oxidative Stress in Aged Sarcopenic Mice Full Text
Novel drug promotes nervous system repair in animal models of stroke Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Age estimation from sleep studies using deep learning predicts life expectancy Full Text
*Epigenetic Age Acceleration Is Correlated with Mortality Full Text
*Biological Age Prediction From Wearable Device Movement Data Identifies Nutritional and Pharmacological Interventions for Healthy Aging Full Text

Blood Factors or other Heterochronic Transplantation
Whole blood exchange could offer disease-modifying therapy for Alzheimer's disease Abstract
Paracrine-mediated rejuvenation of aged mesenchymal stem cells is associated with downregulation of the autophagy-lysosomal pathway Full Text

Epigenetics & Cellular Reprogramming
Diverse partial reprogramming strategies restore youthful gene expression and transiently suppress cell identity Full Text (June 2022)

Exosomes (small packets of information released by cells)
Exosome-based strategy for degenerative disease in orthopedics: Recent progress and perspectives Full Text
Sex Differentially Alters Secretion of Brain Extracellular Vesicles During Aging: A Potential Mechanism for Maintaining Brain Homeostasis Full Text
Cerebral endothelial cell derived small extracellular vesicles improve cognitive function in aged diabetic rats Full Text

Genetics including CRISPR
Mitigation of age-dependent accumulation of defective mitochondrial genomes Full Text
Men lose Y chromosomes as they age. It may be harming their hearts Abstract

Lifespan Lengthening Interventions
Genetic Disruption of KLF1 K74 SUMOylation in Hematopoietic System Promotes Healthy Longevity in Mice Full Text
Chili pepper extends lifespan in a concentration-dependent manner and confers cold resistance on Drosophila melanogaster cohorts by influencing specific metabolic pathways
Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice Full Text

Microbiome
Antioxidative potential of Lactobacillus sp. in ameliorating D-galactose-induced aging Full Text
A rhythmic small intestinal microbiome prevents obesity and type 2 diabetes Full Text
Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives Full Text

Observational Studies
*Association of Low Muscle Mass With Cognitive Function During a 3-Year Follow-up Among Adults Aged 65 to 86 Years in the Canadian Longitudinal Study on Aging Full Text
*Life Course Predictors of Young Men Surviving to Age 90 in a Cohort Study: The Manitoba Follow-up Study Full Text
*Social Frailty Is Correlated with All-Cause Mortality Abstract

Opinion/Editorials/Theory
The importance of elders Full Text
The damage-independent evolution of ageing by selective destruction Full Text
Somatotropic Axis, Pace of Life and Aging Full Text

Other Ageing Biology
Glutamine Supplementation Has Anti-Aging Potential Full Text
mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila Full Text
Sirt1 overexpression improves senescence-associated pulmonary fibrosis induced by vitamin D deficiency through downregulating IL-11 transcription Full Text

Reproductive Health
Short-Term Resveratrol Reverses Ovarian Aging in Mice Full Text
Administration of nicotinamide mononucleotide improves oocyte quality of obese mice Full Text
Lycopene Reduces the In Vitro Aging Phenotypes of Mouse Oocytes by Improving Their Oxidative Status Full Text

Reviews
Human age reversal: Fact or fiction? Full Text
Targeting the “hallmarks of aging” to slow aging and treat age-related disease: fact or fiction? Full Text
Pharmacological Approaches to Decelerate Aging: A Promising Path Full Text
Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations Full Text
Immunomodulatory and Antiaging Mechanisms of Resveratrol, Rapamycin, and Metformin: Focus on mTOR and AMPK Signaling Networks Full Text
Longevity-Promoting Pathways and Transcription Factors Respond to and Control Extracellular Matrix Dynamics During Aging and Disease Full Text
Autophagy in health and disease: From molecular mechanisms to therapeutic target Full Text

Senolytics/Senescent Cells
Elimination of Senescent Cells by Senolytics Facilitates Bony Endplate Microvessel Formation and Mitigates Disc Degeneration in Aged Mice Full Text
Senolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma Full Text
Chronic hyperinsulinemia promotes human hepatocyte senescence Full Text

Skin & Beauty
*Multifaceted amelioration of cutaneous photoageing by (0.3%) retinol
Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorate Skin Aging of Nude Mice Through Autophagy-Mediated Anti-Senescent Mechanism
Anti-Aging Effect of the Stromal Vascular Fraction/Adipose-Derived Stem Cells in a Mouse Model of Skin Aging Induced by UVB Irradiation Full Text

Stem Cells
Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review Full Text
*Effect of Combined Intraosseous and Intraarticular Infiltrations of Autologous Platelet-Rich Plasma on Subchondral Bone Marrow Mesenchymal Stromal Cells from Patients with Hip Osteoarthritis Full Text

Telomeres
Telomere Length Regulation Full Text
*Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol’s effects Full Text
*Leukocyte Telomere Length as a Molecular Biomarker of Coronary Heart Disease Full Text

Odds & Sods
The longevity dividend through inanimate objects in the tales of Hans Christian Andersen Full Text
*Improvement of several stress response and sleep quality hormones in men and women after sleeping in a bed that protects against electromagnetic fields Full Text
*Unconscious mind activates central cardiovascular network and promotes adaptation to microgravity possibly anti-aging during 1-year-long spaceflight Full Text

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***Disclaimer 1 – 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 you need 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 above 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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