February 2019 Longevity Review

Hello and welcome to this month’s longevity update. As I scour the internet for the latest news on the science of anti-ageing I predominantly use scientific news sites and publications, however I also check out non-traditional sources such as blogs and their comment sections to find out hints as to what may be coming down the road. I want to share an exciting example of this.

A few months ago, in the comment section of a blog, somebody posted that their lab had successfully managed to rejuvenate old rats by using a fraction of young blood plasma. Young blood/plasma, along with epigenetic reprogramming, is one of the few anti-aging strategies which has the potential to be a “silver bullet” to cure ageing. The blog poster has now shared their first results with the blog in question. If the results are to be believed, and it’s a big IF as the study only involved 6 rats and has not yet been peer-reviewed, let alone replicated, then it could portend human rejuvenation being less than a decade away.
Rumors of Age Reversal: The Plasma Fraction Cure Study Results

On a personal level, in the past month I’ve gone “all in” on anti-ageing supplements with the start of me taking Rapamycin (2.5mg/weekly) & Metformin (500mg/daily). Not expecting anything myself, but I want to be confident about their safety before giving them to my parents. I bought blood pressure and blood glucose monitors to try to get some biomarkers for what it’s worth.

Below you will find February’s most interesting developments as well as a couple of really cool podcasts. Furthermore, in the supplemental attachment there are some human studies of Curcumin, Nicotinamide Riboside (NR) and Resveratrol – along with an avalanche of promising studies on Rapamycin amongst others.
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February Round-Up

Young bone marrow rejuvenates aging mouse brains - Transplanting bone marrow from young lab mice to old mice preserves memory and learning skills. This is similar to using “young blood” to treat ageing, but instead of transfusing blood, the blood producing cells have been transplanted. Full Text

CRISPR/Cas9 therapy can suppress aging, enhance health and extend life span in mice - Researchers have developed a new gene therapy to help decelerate the aging process. The findings highlight a novel CRISPR/Cas9 genome-editing therapy that can suppress the accelerated aging observed in mice with Hutchinson-Gilford progeria syndrome, a rare genetic disorder that also afflicts humans. This is the first time to my knowledge that CRISPR/Cas9 gene editing has been used in the ageing field – exciting stuff! Full text

New molecules reverse memory loss linked to depression, aging - New therapeutic molecules show promise in reversing the memory loss linked to depression and aging. These molecules not only rapidly improve symptoms, but remarkably, also appear to renew the underlying brain impairments causing memory loss in preclinical models. Full Text

Inhibition of ‘jumping genes’ promotes healthy ageing - DNA sequences called retrotransposons can copy themselves and reintegrate at new sites in the genome, causing damage. It now seems that inhibiting this process can prevent age-related health decline in mice. Full Text

Skin Repair Eliminates ‘Inflamm-Aging’ Linked to Chronic Disease In a pilot study, treatment with a full-body reparative skin cream reduced inflammatory cytokines linked to Alzheimer’s, Heart Disease and Diabetes. Time to slap on the skin cream! Full Text
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Below are two podcasts with leading anti-ageing researcher David Sinclair, who shot to fame in the mid-2000s with the red wine molecule Resveratrol, which lengthened the life of obese mice. Since then his lab has worked on the NAD+ pathway, which is vital for numerous repair processes and declines with age, and small molecules which can return NAD+ to youthful levels. He has been a big proponent of Nicotinamide Mononucleotide (NMN) to do so.

The Joe Roggan Experience – an accessible and entertaining podcast for the layman. This show caused a surge in NMN sales.

Peter Attia – a much more technical podcast getting into the nitty-gritty NAD+, NMN & ageing in general.
https://peterattiamd.../davidsinclair/

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Research Institutes:
SENS Research Foundation (I have a recurring monthly donation)
Buck Institute
Private initiatives:
Age-Reversal Network (good information & forums for those interested in self-experimentation – this is where I found how to get non-prescription Rapamycin)
Better Humans
Lifespan.io (I have a recurring monthly donation)
Further sources of information:
Fight Aging!
Life Extension Advocacy Foundation
Longecity (good forums where the self-experimenters reside!)

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Supplemental Information

**Disclaimer – As should be self-evident to anyone receiving these emails, 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 needing medical advice.**

*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 – 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.
Autophagy and aging: Maintaining the proteome through exercise and caloric restriction. Full Text Interesting how exercising and caloric restriction work on the same pathways as the drug Rapamycin.

Non-prescription Supplements (in alphabetical order)

Astaxanthin – which is behind the pink colour of salmon & shrimp. Considered the most powerful carotinoid, it has anti-oxidative, anti-inflamatory, neuro-protective and skin-protective qualities. I take 4mg daily.

Protective effect of astaxanthin against contrast-induced acute kidney injury via SIRT1-p53 pathway in rats. Full Text
Neuroprotective role of astaxanthin in hippocampal insulin resistance induced by Aβ peptides in animal model of Alzheimer's disease. Full Text
Astaxanthin supplementation modulates cognitive function and synaptic plasticity in young and aged mice. Full Text
Astaxanthin Ameliorates Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress and Memory Dysfunction through Inactivation of the Signal Transducer and Activator of Transcription 3 Pathway. Full Text
Astaxanthin ameliorates renal interstitial fibrosis and peritubular capillary rarefaction in unilateral ureteral obstruction. Full Text
Effects of astaxanthin supplementation in healthy and obese dogs. Full Text

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. I take 1 gram a day. Needs gto be
taken with black pepper to improve bio-availability.

*The therapeutic potential of curcumin: A review of clinical trials. Full Text
*The effects of curcumin-containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Full Text
*Effects of hot water extract of Curcuma longa on human epidermal keratinocytes in vitro and skin conditions in healthy participants: A randomized, double-blind, placebo-controlled trial. Full Text
Curcumin ameliorated myocardial infarction by inhibition of cardiotoxicity - rat model. Full Text
Curcumin prevents high glucose damage in retinal pigment epithelial cells through ERK1/2-mediated activation of the Nrf2/HO-1 pathway Full Text
Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF: Nrf2 and antioxidant mechanisms in skeletal muscle Full Text
Curcumin promotes burn wound healing in mice by upregulating caveolin-1 in epidermal stem cells Full text
Curcumin, the golden spice in treating cardiovascular diseases. Full Text
Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: A review. Full Text
A Review of Curcumin and Its Derivatives as Anticancer Agents. Full Text

Fisetin – a flavonoid found in highest concentration in strawberries. Senolytic, anti-inflammatory, neuro-protective & Sir1 activator. I
newly take 100mg daily.

Fisetin ameliorates oxidative stress, inflammation and apoptosis in diabetic cardiomyopathy. Full Text
Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma. Full Text
Activated TNF-α/RIPK3 signaling is involved in prolonged high fat diet-stimulated hepatic inflammation and lipid accumulation: inhibition by dietary fisetin intervention. Full Text
Nrf2⁻ARE Signaling Acts as Master Pathway for the Cellular Antioxidant Activity of Fisetin. Full Text
Protective effect of Fisetin on acetaminophen-induced hepatotoxicity in vitro and in vivo. Full Text
Fisetin and telmisartan each alone or in low-dose combination alleviate OVA-induced food allergy in mice. Full Text

Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250mg daily.

Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3-dependent mechanism in male mice. Full Text
Targeting NAD+ Metabolism as Interventions for Mitochondrial Disease. Full Text
Enhanced SIRT6 activity abrogates the neurotoxic phenotype of astrocytes expressing ALS-linked mutant SOD1. Full Text
Nicotinamide adenine dinucleotide emerges as a therapeutic target in aging and ischemic conditions. Full Text

Nicotinamide Riboside (NR) – NAD+ precursor.

*Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. Full Text

Pterostilbene – found in blueberries. Anti-oxidant, anti-inflamatory and Sir1 activator. Similar to, but with greater bioavailability than resveratrol. Took some last year (50mg) and will order again. Works better in conjunction with NAD+ precursors.

Pterostilbene Improves Cognitive Performance in Aged Rats: An in Vivo Study. Full Text

Resveratrol – found in the skin of grapes. Anti-oxidant, anti-inflamatory and Sir1 activator. Took a low dose last year (50mg), will order again. Works better in conjunction with NAD+ precursors.

*Effect of resveratrol supplementation on lipid profile in subjects with dyslipidemia: A randomized double-blind, placebo-controlled trial. Full Text
*No beneficial effects of resveratrol supplementation on atherogenic risk factors in patients with nonalcoholic fatty liver disease. Just to prove I don’t just give only positive results, in this study there were no beneficial effects.
*Health benefits of resveratrol: Evidence from clinical studies. Full Text
*The Effects of Resveratrol in Patients with Cardiovascular Disease and Heart Failure: A Narrative Review. Full Text
Health benefits of resveratrol administration. Full Text
Resveratrol as a Multifunctional Topical Hypopigmenting Agent. Full Text

Spermidine – found in wheat germ and a potent inducer of autophagy. Try to eat a couple of tablespoons of wheat germ every day.

Spermidine and Voluntary Activity Exert Differential Effects on Sucrose- Compared with Fat-Induced Systemic Changes in Male Mice. Full Text

Prescription Supplements

Rapamycin – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer. Taken 3 doses of 2.5mg so far with nothing to report. I will increase my dose to 3.75mg after the next one.

Pharmacological inhibition of mTORC1 but not mTORC2 protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism through Akt and autophagy induction. Full Text
Next generation strategies for geroprotection via mTORC1 inhibition. Full Text
The mTORC1-autophagy pathway is a target for senescent cell elimination. Full Text In light of all the recent excitement regarding senolytic drugs, it appears that Rapamycin might also be senolytic, which would account for some of its positive effects.
mTOR inhibition by metformin impacts monosodium urate crystal-induced inflammation and cell death in gout: a prelude to a new add-on therapy? Full Text
Rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis. Full Text
Inhibition of upper small intestinal mTOR lowers plasma glucose levels by inhibiting glucose production. Full Text
Balancing mTOR Signaling and Autophagy in the Treatment of Parkinson's Disease. Full Text
Snapshot: Implications for mTOR in Aging-related Ischemia/Reperfusion Injury. Full Text
Rapamycin Confers Neuroprotection Against Aging-Induced Oxidative Stress, Mitochondrial Dysfunction, and Neurodegeneration in Old Rats Through Activation of Autophagy. Full Text
mTOR signalling: jack-of-all-trades Full Text
Measuring biological age in mice using differential mass spectrometry. Full Text This study is interesting in that giving Rapamycin to the mice reduced their biological age by 18% using their measures.
Single injection of rapamycin blocks post-food restriction hyperphagia and body-weight regain in rats. Rats didn’t regain weight after going off a diet.
Combinatorial Tissue Engineering Partially Restores Function after Spinal Cord Injury. Full Text

Senolytics – not supplements or available now, but the most exciting area of anti-research at the moment. Didn’t want to clog up the main email, so I’ve put any extra studies or news here:

Approaches towards Longevity: Reprogramming, Senolysis, and Improved Mitotic Competence as Anti-Aging Therapies. Full Text
Removing Senescent Cells Improves Heart Health