April 2019 Longevity Review

Hello and welcome once again to this month’s longevity update. There’s no “theme” this month, but plenty of interesting advances from the frontier of ageing research encompassing AGEs, blood factors, stem cells & cellular re-programming. In the supplemental attachment there’s the usual plethora of studies, my favourite about how Rapamycin might prevent sarcopenia (muscle wasting), but also a worrying one about how eating close to bed time & skipping breakfast (which I’m guilty of) might be dangerous.

On a personal level, I took a hiatus from my self-experiment whilst I recovered from my second hand operation, but have now resumed. There’s still nothing to report there, but my parents have finally received their own supply of Rapamycin, so it will be interesting to see if it has any positive effect on them. I joined another longevity organization – the Gerontology Research Group, which, as it has many scientists as members, should provide another source of good information. Also, I’m beginning, at long last, to post more regularly on twitter – follow me @ChrisPollyanna1 for the latest updates.

Finally – please feel free to forward this email to anyone who might be interested, and please let me know if anyone would like to be included in my mailing list!
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NOTE: I’ve been having trouble linking to the science journal hacking site sci-hub.tw, so am only including Full Text links to articles not behind a paywall. I have still been able to download most of them, so if there are any that you are after, I can send them upon request.

April Round-Up

• Advanced Glycation End Products (AGEs) are compounds which are formed when fats & proteins combine with sugars (either during cooking or inside our bodies) to cause problems, such as the stiffening of arteries or wrinkles in the skin, as they accumulate with time. So far, there had been no way to get rid of them once they have formed, however, the study below marks the first time that this has been achieved. Although early days, these are important first steps:

• I’ve talked about in the past about how the replenishment of some factors in blood, which decline with age, might reverse some aspects of ageing (eg GDF11). Conversely, there are factors in blood which increase with age, and their removal might likewise help with ageing. The study below blocked a different protein (CD22) which increases with age, and whose blockage reversed cognitive decline in mice:

• Stem cells, one way or another, are going to be needed in this fight against ageing, however, up until now there has been little definitive proof that the current technology is effective, despite the proliferation of stem cell clinics. Therefore, it is nice to see in the trial below that stem cells are somewhat effective in treating knee osteoarthritis:

• To show what might be eventually possible with stem cells, the study below increased the maximum lifespan of mice by 28% with the transplantation of bone marrow from young to aged animals. This echoes a human study I reported on last year which improved markers of frailty with a transfusion of stem cells:

• One problem with transplanting stem cells is that stem cells themselves age, which is why in the study above, bone marrow was taken from young animals. But what if the old stem cells could be rejuvenated like the silver bullet of cellular re-programming, which I gushed on about last month? Well, how about the study below then, which did precisely that!

• Fortunately, there is a continued push by scientists to find new molecules which might combat ageing. Here is another example of a new class of drugs (Hsp90 inhibitors) being found which extend the lifespan of worms. What makes this study more exciting is not that they found some potential life-extending molecules, but that they further tested them in combination with proven life-extending molecules such as Rapamycin (yeah!) and found that there was a synergistic effect – further increasing the worms lifespans:

• Finally, for something more applicable in the near term, the following study showed how the low dose combination of a Statin and Angiotensin II Receptor Blocker (for blood pressure) can increase the expression of pro-longevity genes in humans:

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In March an anti-ageing conference took place in Berlin (Undoing Aging 2019) which was notable for the level of optimism amongst the attendees. The conference featured much of the who’s who in the ageing research field. All the presentations were recorded and they have now started to be posted onto YouTube. As of this writing only three have been posted, but more will undoubtedly follow. The talks from the previous year’s conference are also available on the page:

https://www.youtube....E6qcTXmKcxkaCGA

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Further sources of information:
Fight Aging!
Life Extension Advocacy Foundation (LEAF)
Longecity (good forums where the crazy self-experimenters reside!)
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
Gerontology Research Group
Lifespan.io (Tied together with LEAF, I have a recurring monthly donation)

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Supplemental Information

***Disclaimer 1 – 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.***

**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 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/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.

*After heart attack: Late dinner and no breakfast a killer combination Full Text
The Impact of Caloric Restriction on the Epigenetic Signatures of Aging. Full Text
Meal Timing, Aging, and Metabolic Health. Full Text

Diet – let food be thy medicine…

Longevity and cause of death in male Wistar rats fed lifelong diets based on virgin olive oil, sunflower oil or fish oil.
*Diet rich in animal protein is associated with a greater risk of early death

Exercise – if you could bottle the benefits of exercise, it would be the biggest blockbuster drug of all time.

*Aerobic Exercise Improves Microvascular Function in Older Adults.
*Effects of high-velocity resistance training and creatine supplementation in untrained healthy aging males.

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, anti-cancer, neuro-protective and skin-protective qualities. I take 4mg daily.

Effects of astaxanthin on sensory-motor function in a compression model of spinal cord injury: Involvement of ERK and AKT signalling pathway. Full Text
Effects of Astaxanthin Supplementation on Oxidative Stress.
Astaxanthin as a Peroxisome Proliferator-Activated Receptor (PPAR) Modulator: Its Therapeutic Implications. Full Text

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

*Metabolic benefits of curcumin supplementation in patients with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.
*Safety and efficacy of curcumin versus diclofenac in knee osteoarthritis: a randomized open-label parallel-arm study. Full Text
*Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial.
*Effects of curcumin on glycemic control and lipid profile in prediabetes and type 2 diabetes mellitus: A systematic review and meta-analysis. Full Text
*Effect of Curcumin Supplementation on Exercise-Induced Oxidative Stress, Inflammation, Muscle Damage, and Muscle Soreness.

Fisetin – a flavonoid found in highest concentration in strawberries. Senolytic, anti-inflammatory, anti-cancer, neuro-protective & Sirt1 activator. I take 100mg daily.

Fisetin and telmisartan each alone or in low-dose combination alleviate OVA-induced food allergy in mice.
Protective effect of Fisetin against angiotensin II-induced apoptosis by activation of IGF-IR-PI3K-Akt signaling in H9c2 cells and spontaneous hypertension rats.

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

Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Full Text
Nicotinamide mononucleotide promotes osteogenesis and reduces adipogenesis by regulating mesenchymal stromal cells via the SIRT1 pathway in aged bone marrow. Full Text

Nicotinamide Riboside (NR) – NAD+ precursor.

Cardioprotective Effect of the Mitochondrial Unfolded Protein Response During Chronic Pressure Overload. Full Text

Pterostilbene – found in blueberries. Anti-oxidant, anti-inflamatory and Sir1 activator. Similar to, but with greater bioavailability than resveratrol. Just started taking 50mg again daily. Works better in conjunction with NAD+ precursors.

Pterostilbene Reduces Liver Steatosis and Modifies Hepatic Fatty Acid Profile in Obese Rats. Full Text

Resveratrol – found in the skin of grapes. Anti-oxidant, anti-inflamatory and Sir1 activator. Just started taking 250mg a day. Works better in conjunction with NAD+ precursors & Spermidine.

Can Resveratrol Treatment Control the Progression of Induced Periodontal Disease? A Systematic Review and Meta-Analysis of Preclinical Studies. Full Text
The roles of sirtuin 1 and its activator, resveratrol in osteoarthritis. Full Text
Preventive role of Resveratrol against inflammatory cytokines and related diseases

Spermidine – found in wheat germ and a potent inducer of autophagy, it works in synergy with Resveratrol. I try to eat a couple of tablespoons of wheat germ every day.

Spermine and gene methylation: a mechanism of lifespan extension induced by polyamine-rich diet.

Prescription Supplements

Rapamycin – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer. Have taken four doses of 2.5mg, four at 3.75mg and will be moving to 5mg once my surgical wounds have closed up (it delays wound healing).

Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling. Full Text
Alzheimer’s - Rapamycin regulates cholesterol biosynthesis and cytoplasmic ribosomal proteins in hippocampus and temporal lobe of APP/PS1 mouse.
Osteoarthritis - Rapamycin Inhibits Nf-ΚB Activation by Autophagy to Reduce Catabolism in Human Chondrocytes.
Progeria -Presence and distribution of progerin in HGPS cells is ameliorated by drugs that impact on the mevalonate and mTOR pathways.
Rapamycin relieves inflammation of experimental autoimmune encephalomyelitis by altering the balance of Treg/Th17 in a mouse model.
Inhibition of mTORC1 signaling in aged rats counteracts the decline in muscle mass and reverses multiple parameters of muscle signaling associated with sarcopenia Full Text
Interesting paper on how Rapamycin induces reversible infertility in men – which could either be a good or bad thing!
Molecular Mechanisms Controlled by mTOR in Male Reproductive System. Full Text

Senolytics – not supplements or available now, but the most exciting area of anti-research at the moment. I intend to take the plunge into senolytics within the next year, before giving them to my parents:

Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model.
Senescence cell-associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers. Full Text
Targeting Cell Senescence for the Treatment of Age-Related Bone Loss.