August 2023 Longevity Review

Posted by Chris Pollyanna , 26 September 2023 · 1,381 views

supplements nmn nad+ fasting diet exercise

The dog days of summer might not have been conducive for productivity, but that didn’t stop plenty of longevity studies being published. A trio of papers showcased the potential of a platelet factor to mimic the benefits of exercise, while combining Metformin & Galantamine might be the solution for muscle wasting. A universal ageing clock for mammals teased the possibility of common causes and treatments for ageing, while gene therapy indicated that longevity promoting genes could be transferred across mammalian species. And finally, the power of combinations was once again demonstrated (this time by Canadian researchers!) for invertebrate disc degeneration.

The supplemental section is also worth checking out in particular for the overviews of the human use of NMN, NR and Urolithin A.

Video TalkThrough of this Newsletter

Canadian Longevity Association News

You might have missed last month’s announcement that we have set up the ability to receive donations via Zeffy, a Canadian donations platform which passes on 100% of your contributions. Your donation will be used to cover our operating expenses, grow our website and social media presence, and galvanise our outreach & advocacy efforts by hosting events among other things. Because we are still small, but growing, even a tiny donation would make a big difference to us!

Speaking of events, we are restarting monthly meet-ups in Toronto, beginning with a celebration of International Longevity Day on Sunday, 1st October in Toronto. The plan is to meet by the 3D Toronto sign in front of City Hall at 2pm for a group photo before heading someplace for food and drinks and the chance to chat and meet fellow longevity enthusiasts. Check out our social media for any updates.

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August 2023 Round-Up:

A trio of papers from the same research team showed that a factor (PF4) released by platelets, which cause blood to clot, can have beneficial effects similar to that of exercise, including restoring cognition and enhancing neuron generation in aged mice. On top of that, as one of the components of young blood, PF4 also shifted their immune system to a more youthful state and reduced brain inflammation. This could be useful to those too frail (or lazy!) to exercise.
A Potential Exercise Mimetic to Restore Youthful Memory Full Text
Platelet factors attenuate inflammation and rescue cognition in ageing Full Text
Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice Full Text

The Naked Mole Rat (NMR) has long intrigued scientists as the longest lived rodent which also almost never gets cancer and shows little deterioration before death. Here, the NMR’s gene for hyaluronic acid was transferred to mice which resulted in significantly less cancer, improved overall health and a modest increase in lifespan of 4%. This work demonstrated that beneficial longevity genes can be utilised by other species, and as one of the authors stated: "Our next goal is to transfer this benefit to humans."
Longevity gene from naked mole rats extends lifespan of mice Lifespan.io Review Abstract

Here, researchers have developed an epigenetic clock which works across all mammals tested, including humans. The significance of this is that it implies the ageing process is conserved across all mammals and therefore what works in mice should also work for us. In addition, in the great debate over whether ageing is deterministic or stochastic, this paper makes “a compelling case that aging is not solely a consequence of random cellular damage accrued in time.” By better understanding the ageing process, we can make better interventions and have a better chance of stopping it.
Universal DNA methylation age across mammalian tissues Full Text

The pathological loss of muscle with age, or sarcopenia, is a debilitating condition which is difficult to combat. Here, researchers found that the combination of metformin and galantamine significantly improved strength and endurance in mice, which neither did individually.
This combination also synergistically increased the lifespan of worms by 22%. As both drugs are approved for human use, it should be easier to move into human testing.
A Metformin and Galantamine Combination for Sarcopenia Full Text

And finally, ending with some Canadian senolytic content (it’s great to see such research taking place in Canada!), which also ticks the box of using a combinatorial approach. In this study for intervertebral disc degeneration, the authors found that the combination of the two selected senolytics reduced the senescent cell burden from 19% to 3.74% compared to 10.31% for the best single agent. Although this was done in vitro, they used 3D cell cultures which more closely mimic real tissue.
Senolytics as a Potential Back Pain Treatment Full Text

Supplemental Section

Lifestyle
*Impact of lifestyle risk factors on admission to nursing home care: a cohort study of 127 108 people aged 60 years and over Full Text
*Diversity in Daily Activities Might Slow Cognitive Decline 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.
*Early time-restricted eating advances sleep in late sleepers: a pilot randomized controlled trial
Intermittent fasting improves Alzheimer's pathology, study shows Full Text
*Short-term intensive fasting enhances the immune function of red blood cells in humans Full Text

Diet – let food be thy medicine…
*Impact of Plant-Based Diets on Biological Aging Full Text
*Associations between protein to non-protein ratio and intakes of other dietary components in a cohort aged 65-75 years: the Nutrition for Healthy Living Study Full Text
Protective Effects of Micronutrient Supplements, Phytochemicals and Phytochemical-Rich Beverages and Foods Against DNA Damage in Humans: A Systematic Review of Randomized Controlled Trials and Prospective Studies Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*Mind body exercise improves cognitive function more than aerobic- and resistance exercise in healthy adults aged 55 years and older – an umbrella review Full Text
*Impact of exercise and leucine-enriched protein supplementation on physical function, body composition, and inflammation in pre-frail older adults: a quasi-experimental study Full Text
*Aerobic exercise, an effective prevention and treatment for mild cognitive impairment Full Text

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.
In vivo protective efficacy of astaxanthin against ionizing radiation-induced DNA damage
Astaxanthin enhances autophagy, amyloid beta clearance and exerts anti-inflammatory effects in in vitro models of Alzheimer’s disease-related blood brain barrier dysfunction and inflammation Full Text
Preventative and Therapeutic Effects of Astaxanthin on NAFLD 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.
An Overview of the Enhanced Effects of Curcumin and Chemotherapeutic Agents in Combined Cancer Treatments Full Text

Fisetin
Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies Full Text
Fisetin Reduces Senescence in the Brains of Sheep 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.
Therapeutic Benefit of Melatonin in Choroidal Neovascularization During Aging Through the Regulation of Senescent Macrophage/Microglia Polarization Full Text
Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury Full Text
*Melatonin Supplementation Reduces Nighttime Blood Pressure But Does Not Affect Blood Pressure Reactivity in Normotensive Adults on a High Sodium Diet

Nicotinamide MonoNucleotide (NMN)
*The Safety and Anti-Ageing Effects of Nicotinamide Mononucleotide in Human Clinical Trials: An Update Full Text
*Fingerstick blood assay maps real-world NAD+ disparity across gender and age Full Text
Role and Potential Mechanisms of Nicotinamide Mononucleotide in Aging Full Text (July 2023)

Nicotinamide Riboside (NR)
Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives Full Text
*Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects Full Text
SUPPLEMENTATION WITH NICOTINAMIDE RIBOSIDE ATTENUATES T CELL EXHAUSTION AND IMPROVES SURVIVAL IN SEPSIS Full Text
Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice Full Text

Pterostilbene
Pterostilbene alleviated cerebral ischemia/reperfusion-induced blood–brain barrier dysfunction via inhibiting early endothelial cytoskeleton reorganization and late basement membrane degradation Full Text
Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent manner Full Text

Resveratrol
Resveratrol, a Multitasking Molecule That Improves Skeletal Muscle Health Full Text

Spermidine
Association of spermidine blood levels with microstructure of sleep—implications from a population-based study Full Text

Other available supplements (in alphabetical order)
*Collagen peptides supplementation improves function, pain, and physical and mental outcomes in active adults Full Text
Controlling Chronic Diseases and Acute Infections with Vitamin D Sufficiency Full Text
Ergothioneine and its congeners: Anti-ageing mechanisms and pharmacophore biosynthesis Full Text
*Cost-Effectiveness of Glucosamine in Osteoarthritis Treatment: A Systematic Review Full Text
Ginsenoside Rc, an Active Component of Panax ginseng, Alleviates Oxidative Stress-Induced Muscle Atrophy via Improvement of Mitochondrial Biogenesis Full Text
Hesperidin Ameliorates Sarcopenia through the Regulation of Inflammaging and the AKT/mTOR/FoxO3a Signaling Pathway in 22–26-Month-Old Mice Full Text
*Modulation of inflammation and immunity by omega-3 fatty acids: a possible role for prevention and to halt disease progression in autoimmune, viral, and age-related disorders Full Text
*Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review Full Text (July 2023)
Nuclear factor erythrogen-2 associated factor 2 (Nrf2) signaling is an essential molecular pathway for the anti-aging effect of whey protein in the prefrontal cortex of aging rat model (Histological and Biochemical Study)
*Effectiveness of Whey Protein Supplementation during Resistance Exercise Training on Skeletal Muscle Mass and Strength in Older People with Sarcopenia: A Systematic Review and Meta-Analysis Full Text

Combinations of Supplements
Antioxidants Rescue Cognitive Decline in Mice Full Text
Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade Full Text

Prescription Supplements

Metformin
Metformin Protects Against Noise-Induced Hearing Loss in Male Mice
*Effect of Metformin Use on Vitamin B12 Deficiency Over Time (EMBER): A Real-World Evidence Database Study Full Text
Metformin beyond an anti-diabetic agent: A comprehensive and mechanistic review on its effects against natural and chemical toxins Full Text

Rapamycin (sirolimus)
*Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis Full Text
*Reduced Prevalence of Dementia in Patients Prescribed Tacrolimus, Sirolimus, or Cyclosporine Full Text
Pharmacokinetics of Sirolimus Eye Drops Following Topical Ocular Administration in Rabbits

Miscellaneous Molecules & Prescription Drugs
*Functional and Clinical Importance of SGLT2-inhibitors in Frailty: From the Kidney to the Heart Full Text (July 2023)
Empagliflozin decreases ageing-associated arterial stiffnening and decreases vascular fibrosis under normoglycemic conditions

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
Biomarkers of Aging for Facilitating Future Research Full Text
Biomarkers of aging in frailty and age-associated disorders: state of the art and future perspective Full Text
Biomarker Study Returns Surprising Results Full Text

Blood Factors or other Heterochronic Transplantation
The rejuvenating influence of young plasma on aged intestine Full Text

Epigenetics & Cellular Reprogramming
DNA methylation networks underlying mammalian traits
p16High senescence restricts cellular plasticity during somatic cell reprogramming
Transient naive reprogramming corrects hiPS cells functionally and epigenetically Full Text
Cellular plasticity in reprogramming, rejuvenation and tumorigenesis: a pioneer TF perspective Full Text
Application of the Yamanaka Transcription Factors Oct4, Sox2, Klf4, and c-Myc from the Laboratory to the Clinic Full Text

Exosomes (small packets of information released by cells)
Exosomes secreted by mesenchymal stem cells delay brain aging by upregulating SIRT1 expression Full Text
Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice Full Text
M2 Microglial Extracellular Vesicles Attenuated Blood-brain Barrier Disruption via MiR-23a-5p in Cerebral Ischemic Mice Full Text

Genetics including CRISPR
Multivariate genome-wide analysis of aging-related traits identifies novel loci and new drug targets for healthy aging Full Text
BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice Full Text
AAV-Mediated nuclear localized PGC1α4 delivery in muscle ameliorates sarcopenia and aging-associated metabolic dysfunctions Full Text

Lifespan Lengthening Interventions
Jumping Genes Influence the Speed of Aging in Worms Full Text

Microbiome
Insights into the genetic influences of the microbiota on the life span of a host Full Text
*An Investigation into the Relationship of Circulating Gut Microbiome Molecules and Inflammatory Markers with the Risk of Incident Dementia in Later Life Full Text
*Behaviour and sun exposure in holidaymakers alters skin microbiota composition and diversity Full Text

Observational Studies
*The association of previous night's sleep duration with cognitive function among older adults: a pooled analysis of three Finnish cohorts Full Text
*Environmental and genetic predictors of human cardiovascular ageing Full Text
*Elevated Plasma Levels of Ketone Bodies Are Associated With All‐Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS Full Text

Opinion/Editorials/Theory
Challenges in developing Geroscience trials Full Text
Precision Nutrition: The Hype Is Exceeding the Science and Evidentiary Standards Needed to Inform Public Health Recommendations for Prevention of Chronic Disease Full Text
The evolution of selective autophagy as a mechanism of oxidative stress response Full Text
Hormesis Defines The Limits Of Lifespan Full Text

Other Ageing Biology
Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2 % hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival Full Text
Downregulation of Krüppel-like factor 14 accelerated cellular senescence and aging Full Text
Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging Full Text
Proteomic changes induced by longevity-promoting interventions in mice

Regenerative Medicine
Biomimetic approach for an articular cartilage patch: combination of decellularized cartilage matrix and silk-elastin-like-protein (SELP) hydrogel
Engineering of extracellular matrix from human iPSC-mesenchymal progenitors to enhance osteogenic capacity of human bone marrow stromal cells independent of their age Full Text

Reproductive Health
Human umbilical cord mesenchymal stem cell‑derived exosomes improve ovarian function in natural aging by inhibiting apoptosis Full Text
The Role of Lifestyle and Dietary Factors in the Development of Premature Ovarian Insufficiency Full Text
*Effects of resveratrol on polycystic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials

Reviews
Mitophagy-promoting agents and their ability to promote healthy-aging Full Text
Challenges in anti-aging medicine–trends in biomarker discovery and therapeutic interventions for a healthy lifespan Full Text
Myc beyond Cancer: Regulation of Mammalian Tissue Regeneration Full Text
Modulation of DNA methylation by one-carbon metabolism: a milestone for healthy aging Full Text

Senolytics/Senescent Cells
Senolytic therapy is neuroprotective and improves functional outcome long-term after traumatic brain injury in mice Full Text
Cellular Senescence Contributes to Large Elastic Artery Stiffening and Endothelial Dysfunction With Aging: Amelioration With Senolytic Treatment
NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates

Skin & Beauty
*A clinical evaluation of the efficacy and tolerability of a novel topical antioxidant formulation featuring vitamin C, astaxanthin, and fermented turmeric Full Text
*Effects of oral intake fruit or fruit extract on skin aging in healthy adults: a systematic review and Meta-analysis of randomized controlled trials Full Text
*Natural Retinol Analogs Potentiate the Effects of Retinal on Aged and Photodamaged Skin: Results from In Vitro to Clinical Studies Full Text

Stem Cells
Restoring Helper Cell Function to Fight Alzheimer’s Full Text
Knockdown of long noncoding RNA SAN rejuvenates aged adipose-derived stem cells via miR-143-3p/ADD3 axis Full Text
*Cell therapy that repairs cornea damage with patient's own stem cells achieves positive phase I trial results Full Text

Telomeres
*Does physical activity moderate the association between shorter leukocyte telomere length and incident coronary heart disease? Data from 54,180 UK Biobank participants Full Text
*Telomere length and chronological age across the human lifespan: A systematic review and meta-analysis of 414 study samples including 743,019 individuals

**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 *starred any human trials.*
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