February 2024 Longevity Review

As we get past the heart of winter, this month we will take a look at how partial reprogramming extends the remaining lifespan of old naturally aged mice; how the Fasting Mimicking Diet reduces biological age; a comparison of intermittent versus continuous dosing of rapamycin in mice; and, a human senolytic trial which raises some concerning questions.

In the supplemental section, you will find additional studies on protein sources and their effect on ageing; a reanalysis of an NMN human trial showing a dose response; the combination of choline and B12 on cognitive impairment; a systematic review of rapamycin in humans for ageing; young plasma for chronic kidney disease progression; modulating the gut microbiome to improve cognitive function; and a link between spirituality and longevity. Plus of course much more!

Canadian Longevity Association News

We had our first board meeting in February, which marks an important milestone in becoming a more professional organization. The CLA also attended a Life Sciences Ontario networking event and visited Dr Karim Mekail, who is doing some amazing longevity research at the U of T, and who has agreed to join our nascent scientific advisory board.

Donate to the Canadian Longevity Association

Please also follow, or join us on social media:

Twitter/X (I also have a personal account with more frequent longevity updates)

Facebook Instagram LinkedIn Meetup

Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.

Discord for longevity related chats and the place to have all your longevity related questions answered.

Previous newsletters can be found in the CLA Facebook Group, and also my Patreon account, which includes bonus material for supporters if you want to buy us a coffee.
Finally, we are always looking for more help or volunteers, regardless of your skill set or time availability. If you’d be interested in helping us, please fill out this Volunteer Registration Form.

February 2024 Round-Up:

Partial reprogramming is one of the hot areas in longevity research and shows great potential. But, until now we haven’t known what lifespan effects it has in normal aged mice. This study puts an end to that by showing that when given to mice at the equivalent human age of 77, it increased remaining lifespan by 109%.
Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice Full Text

Fasting has many beneficial effects, especially if it can be done over multiple days, yet it is hard to accomplish. The Fasting Mimicking Diet (FMD) seeks to make it easier by providing a minimal amount of food and reduced protein over five days while maintaining the benefits. In this latest study, it reduced participants' median biological age by 2.5 years.
*Fasting-Mimicking Diet Might Extend Lifespan in Humans Full Text

There is no longer any question that rapamycin can extend health and lifespan (in mice at least!), but what treatment regime should be used is still up for question. This study, once again in mice, compares the sex specific effects between continuous and intermittent dosing. Continuous dosing overall had greater benefits, but one week on/off kept a lot of those benefits while reducing some side effects.
Intermittent Rapamycin Lessens Negative Effects in Mice Full Text

Finally another senolytic clinical has released its results using Dasatinib & Quercetin in the first part, before Fisetin was added to the mix in the second half. The study sought to see how various epigenetic clocks responded to these senolytics, and it turned out to be a bit of a mixed bag, with there being some age acceleration with some of the clocks.
*Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on senolytic interventions Full Text

Supplemental Section

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.
*Effectiveness of an intermittent fasting diet versus regular diet on fat loss in overweight and obese middle-aged and olderly people without metabolic disease: a systematic review and meta-analysis of randomized controlled trials Full Text
Short-term periodic restricted feeding elicits metabolome-microbiome signatures with sex dimorphic persistence in primate intervention Full Text
Short-term fasting of a single amino acid extends lifespan Full Text

Diet – let food be thy medicine…
Eating too much protein is bad for your arteries, and this amino acid is to blame Abstract
*Empirically derived dietary patterns are associated with major adverse cardiovascular events, all-cause mortality, and congestive cardiac failure in older men: The Concord Health and Ageing in Men Project Full Text
*The MIND diet for the ageing brain: a systematic review Full Text
*Dietary protein intake in midlife in relation to healthy aging – results from the prospective Nurses’ Health Study cohort Full Text

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.
*High-intensity acute exercise impacts motor learning in healthy older adults Full Text
*Enhanced memory and hippocampal connectivity in humans 2 days after brief resistance exercise Full Text
*The intensity paradox: A systematic review and meta-analysis of its impact on the cardiorespiratory fitness of older adults Full Text
*Sedentary behavior increases mortality risk 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.
*The effects of astaxanthin supplementation on liver enzymes levels

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. Needs to be taken with black pepper (piperine) to improve bioavailability.
Curcumin Improves Functional Recovery of Ruptured Tendon by Promoting Tenogenesis via PI3K/Akt Signaling Full Text

Fisetin
Fisetin orchestrates neuroinflammation resolution and facilitates spinal cord injury recovery through enhanced autophagy in pro-inflammatory glial cells

Melatonin
*The Effect of Melatonin Supplement on High Arterial Blood Pressure: An Overview from Clinicaltrials.gov Full Text
Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities Full Text
*The Effect of Melatonin Supplementation on Cancer-Related Fatigue during Chemotherapy Treatment of Breast Cancer Patients: A Double-Blind, Randomized Controlled Study Full Text

Nicotinamide MonoNucleotide (NMN)
*Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration Full Text
β-Nicotinamide Mononucleotide Promotes Cell Proliferation and Hair Growth by Reducing Oxidative Stress Full Text
Glycolysis-Mediated Activation of v-ATPase by Nicotinamide Mononucleotide Ameliorates Lipid-Induced Cardiomyopathy by Repressing the CD36-TLR4 Axis Full Text

Nicotinamide Riboside (NR)
Comparison of protective effects of nicotinamide mononucleotide and nicotinamide riboside on DNA damage induced by cisplatin in HeLa cells Full Text
Nicotinamide Riboside Regulates Chemotaxis to Decrease Inflammation and Ameliorate Functional Recovery Following Spinal Cord Injury in Mice Full Text

Pterostilbene
Design, synthesis, in vitro and in vivo biological evaluation of pterostilbene derivatives for anti-inflammation therapy Full Text

Resveratrol
Resveratrol prevents age-related heart impairment through inhibiting the Notch/NF-κB pathway Full Text
A novel model of sensorineural hearing loss induced by repeated exposure to moderate noise in mice: the preventive effect of resveratrol Full Text
*Effects of resveratrol on the anthropometric indices and inflammatory markers: an umbrella meta-analysis

Spermidine
Spermidine ameliorates osteoarthritis via altering macrophage polarization
Synergistic effect of spermidine and ciprofloxacin against Alzheimer's disease in male rat via ferroptosis modulation

Other available supplements or natural substances (in alphabetical order)
Caffeine Ameliorates Age-Related Hearing Loss by Downregulating the Inflammatory Pathway in Mice Full Text
Glycine supplementation can partially restore oxidative stress associated glutathione deficiency in ageing cats
Effects of Ferulic Acid on Cognitive Function: A Systematic Review Full Text
Magnesium and the Hallmarks of Aging Full Text
*An analysis of omega-3 clinical trials and a call for personalized supplementation for dementia prevention Full Text

Combinations of Supplements
*Combining Choline Bitartrate and Vitamin B12 Ameliorates Cognitive Impairment in Hypertensive Elders with Cognitive Frailty Full Text
The Potential Use of Vitamin D3 and Phytochemicals for Their Anti-Ageing Effects Full Text

Prescription Supplements

Metformin
Examining the clinical relevance of metformin as an antioxidant intervention Full Text

Rapamycin (sirolimus)
The Latest in Rapamycin Research on Humans Full Text
Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion Full Text
Rapamycin rescues loss-of-function in blood-brain barrier-interacting regulatory T cells Full Text

Miscellaneous Molecules & Prescription Drugs
Minocycline alleviates LPS-induced cognitive dysfunction in mice by inhibiting the NLRP3/caspase-1 pathway Full Text

Novel Molecules
COP-22 Alleviates D-Galactose–Induced Brain Aging by Attenuating Oxidative Stress, Inflammation, and Apoptosis in Mice Full Text

Other Areas of Interest (in alphabetical order)

Ageing Clocks & other biomarkers of ageing
*Epigenetic Clocks Help Predict Health Outcomes Full Text
Aging clock based on nucleosome reorganisation derived from cell-free DNA Full Text
Genome-wide transcriptome profiling and development of age prediction models in the human brain Full Text

Blood Factors or other Heterochronic Transplantation
Young Plasma Attenuated Chronic Kidney Disease Progression after Acute Kidney Injury by Inhibiting Inflammation in Mice Full Text

Epigenetics & Cellular Reprogramming
Cell Reprogramming Strategies for Treating Osteoarthritis and Intervertebral Disc Degeneration Full Text
Cellular reprogramming as a tool to model human aging in a dish Full Text

Exosomes (small packets of information released by cells)
Myogenic exosome miR-140-5p modulates skeletal muscle regeneration and injury repair by regulating muscle satellite cells Full Text
Extracellular vesicles from UTX-knockout endothelial cells boost neural stem cell differentiation in spinal cord injury Full Text

Genetics including CRISPR
Therapeutic potential of AAV-FL-Klotho in obesity: Impact on weight loss and lipid metabolism in mice

Lifespan Lengthening Interventions
Restricting bioenergetic efficiency enhances longevity and mitochondrial redox capacity in Drosophila melanogaster Full Text
Betulinic Acid Increases the Lifespan of Drosophila melanogaster via Sir2 and FoxO Activation Full Text
Endogenous chondroitin extends the lifespan and healthspan in C. elegans Full Text

Microbiome
*Probiotics supplementation or probiotic-fortified products on sarcopenic indices in older adults: systematic review and meta-analysis from recent randomized controlled trials Full Text
*Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness Full Text
*Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial Full Text
*Association of dietary live microbe intake with frailty in US adults: evidence from NHANES Full Text

Observational Studies
*Higher Abdominal Fat Associated with Cognitive Decline Full Text
*Consequences of heterogeneity in aging: parental age at death predicts midlife all-cause mortality and hospitalization in a Swedish national birth cohort Full Text
*Comparison of three frailty measures for predicting hospitalization and mortality in the Canadian Longitudinal Study on Aging Full Text CAN

Opinion/Editorials/Theory
Why death and aging ? All memories are imperfect
Is Aging a Disease? A Critical Review Within the Framework of Ageism Full Text
A unified framework for evolutionary genetic and physiological theories of aging Full Text

Other Ageing Biology
Pharmacological interventions in human aging database
Restoration of norepinephrine release, cognitive performance, and dendritic spines by amphetamine in aged rat brain Full Text
Age-, sex- and proximal–distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates Full Text
PandaOmics: An AI-Driven Platform for Therapeutic Target and Biomarker Discovery Full Text CAN

Reproductive Health
The Antioxidant Salidroside Ameliorates the Quality of Postovulatory Aged Oocyte and Embryo Development in Mice Full Text
Cellular senescence in the pathogenesis of ovarian dysfunction Full Text
Senolytic treatment fails to improve ovarian reserve or fertility in female mice
New insights into ginsenoside Rg1 regulating the niche to inhibit age-induced germline stem cells depletion through targeting ECR/BMP signaling pathway in Drosophila Full Text

Reviews
The therapeutic perspective of NAD+ precursors in age-related diseases Full Text
The interplay between obesity, immunosenescence, and insulin resistance Full Text
The salamander limb: a perfect model to understand imperfect integration during skeletal regeneration Full Text

Senolytics/Senescent Cells
MicroRNA-146a gene transfer ameliorates senescence and senescence-associated secretory phenotypes in tendinopathic tenocytes Full Text
Cellular senescence: Neither irreversible nor reversible Full Text
Senolytics: from pharmacological inhibitors to immunotherapies, a promising future for patients’ treatment Full Text

Skin & Beauty
*Polynucleotides HPT for Asian Skin Regeneration and Rejuvenation Full Text
Dietary Isoeugenol Supplementation Attenuates Chronic UVB-Induced Skin Photoaging and Modulates Gut Microbiota in Mice Full Text
*Evaluation of an advanced antioxidant and double-conjugated retinoid/AHA cream in participants with FST IV–V Full Text

Stem Cells
MiR-145-5p overexpression rejuvenates aged adipose stem cells and accelerates wound healing Full Text
Mesenchymal Stem Cell Transplantation Has a Regenerative Effect in Ischemic Myocardium: An Experimental Rat Model Evaluated by SPECT-CT Assessment Full Text
MSX1+PDGFRAlow limb mesenchyme-like cells as an efficient stem cell source for human cartilage regeneration Full Text

Telomeres
*Association between modifiable lifestyle factors and telomere length: a univariable and multivariable Mendelian randomization study Full Text

Odds & Sods
Cumulative Deleterious Effects of Tetrahydrocannabinoid (THC) and Ethanol on Mitochondrial Respiration and Reactive Oxygen Species Production Are Enhanced in Old Isolated Cardiac Mitochondria Full Text
Enriched oxygen improves age-related cognitive impairment through enhancing autophagy Full Text
The link between spirituality and longevity Full Text
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
***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 *starred any human trials.*
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------