June 2019 Longevity Review

Hello and welcome once again to this month’s longevity update. The big news for June was the release of the second set of human trial results for a senolytic agent, which although did not produce miracles, was nevertheless very encouraging in my opinion.

 

The big news from me is that I volunteered at Ending Age Related Diseases 2019 in New York on 11^th-12^th July. I got to be one of the two timekeepers and therefore got to watch all of the presentations and discussions from the front row. It was an amazing, yet exhausting experience – who knew that simply keeping track of time could be so tiring? I will mention more next month, as I want to get this update out, having originally planned to get it out before I went. I had also planned to live tweet the event but there wasn’t any time – speaking of which…

 

Follow me on Twitter @ChrisPollyanna1 for the latest updates!

 

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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.

 

June Round-Up

• Senolytics are the most promising near term rejuvenatory therapeutics. If the data from mice in any way translates to humans, then their impact will be profound. Here is the second set of preliminary results in humans (the first being in January with a different drug combo). This is from a commercial company hoping to bring it to market against arthritis initially. This was a phase 1 study, so it was meant to check for any potential side effects, not how well it worked. There were no major side effects and initial indications of a dose response, which is extremely encouraging. To my surprise the longevity community didn’t do cartwheels of joy, but I think most of them didn’t dig into the results or watch the company presentation, which I have included here for the added detail:

*Unity Biotechnology Releases UBX0101 Results Unity Conference Call with Powerpoint

• Even if you were to make it to 110 years of age without suffering any of the major diseases of ageing, something will still get you in the end. That “something” turns out to be amyloidosis, the deposition of amyloid throughout the body, which was found to be the main cause of death among supercentenarians. I realise this must be keeping you awake at night! Fear not however, as the first in human trial of a drug to treat this most pressing of conditions has taken place:

*First-in-Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers. Full Text

• Urolithin A is a substance which our gut microbes can produce from a molecule found in pomegranate (ellagitannins) and which might help our mitochondria (the powerhouse of our cells). Urolithin A has been found to increase the lifespan of model organisms, however even more interestingly, the study below was done in humans and although was not aimed at improving lifespan, showed an improvement in their mitochondria. For those of you who like to go down the rabbit hole, I’ve also included a link to a video review of the paper by LEAF, who review a longevity paper every month on their Facebook page:

*Positive Results from Urolithin A Human Trial LEAF Journal Club June edition on Urolithin A paper

• Here is another study showing that a means of increasing NAD+ in the body (of mice) could increase lifespan by around 16%, this time using a protein, eNAMPT, which declines with age. This is hopeful for those of us who take NAD+ precursors such as Nicotinamide Mononucleuotide (NMN) or Nicotinamide Riboside (NR).

NAMPT Delays Aging and Extends Lifespan in Mice

• I’ve mentioned many times before about the potential benefits of transferring young blood or plasma to older individuals. Here is a rather different proposition entirely! It turns out that the composition of our gut microbes changes with age, and by transplanting the gut microbes of a young mouse to an old one improves one aspect of ageing:

Transplanting Gut Microbes from Young to Old Mice Reverses Immune Decline Full Text

• The thymus is a vital organ of our immune system which unfortunately shrinks with age. If the thymus could be rejuvenated, out immune system would improve and reduce the incidence of life threatening infections, which are significant source of mortality for the elderly. Here, scientists have made progress in engineering a man made replacement for the thymus’s decline:

Creating Thymus Organoids Using Tissue Engineering Full Text

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Videos to watch – as I’ve already given a couple of things to watch in the round-up section above, there’s nothing extra this month. Not to mention I didn’t find anything else worth putting in here…
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Further sources of information:
Fight Aging!
Life Extension Advocacy Foundation (LEAF)
Longecity (good forums where the 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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June 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.

 

*The Effects of Time Restricted Feeding on Overweight, Older Adults: A Pilot Study Full Text
Time-restricted feeding delays the emergence of the age-associated, neoplastic-prone tissue landscape. Full Text
Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruption Full Text
Dietary restriction induces posttranscriptional regulation of longevity genes. Full Text

 

Diet – let food be thy medicine…

 

*Positive Associations of Dietary Marine Omega-3 Polyunsaturated Fatty Acids with Lung Function: A Meta-analysis Full Text
*Strawberry Consumption Associated with Reduced Alzheimer's Dementia Risk Full Text
*Garlic Consumption and All-Cause Mortality among Chinese Oldest-Old Individuals: A Population-Based Cohort Study. Full Text
Habitual tea drinking modulates brain efficiency: evidence from brain connectivity evaluation. Full Text
Lycopene inhibits smoke-induced chronic obstructive pulmonary disease and lung carcinogenesis by modulating reverse cholesterol transport in ferrets.
Protective effect of green tea catechin against urban fine dust particle-induced skin aging by regulation of NF-κB, AP-1, and MAPKs signaling pathways

 

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

 

*Resistance Exercise Training as a Primary Countermeasure to Age-Related Chronic Disease Full Text
*Strength training and protein supplementation improve muscle mass, strength, and function in mobility-limited older adults: a randomized controlled trial.
*Exercise Reverses Age‐Related Decline in NAD+ Salvage Capacity Full Text

 

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.

 

Astaxanthin Inhibits Alcohol-induced Inflammation and Oxidative Stress in Macrophages Full Text
Astaxanthin protects against renal fibrosis through inhibiting myofibroblast activation and promoting CD8+ T cell recruitment.

 

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.

 

*Curcuminoids plus piperine improve nonalcoholic fatty liver disease: A clinical trial.
*Effects of curcumin supplementation on markers of inflammation and oxidative stress among healthy overweight and obese girl adolescents: A randomized placebo-controlled clinical trial.
*Evaluation of the efficacy and safety of Capsule Longvida® Optimized Curcumin (solid lipid curcumin particles) in knee osteoarthritis: a pilot clinical study. Full Text
*A Highly Bioavailable Curcumin Extract Improves Neurocognitive Function and Mood in Healthy Older People: A 12-Week Randomised, Double-Blind, Placebo-Controlled Trial Full Text
Benefits of curcumin in brain disorders.

 

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

 

Phytomedicine-Based Potent Antioxidant, Fisetin Protects CNS-Insult LPS-Induced Oxidative Stress-Mediated Neurodegeneration and Memory Impairment. Full Text
Induction of endothelial dysfunction by oxidized low-density lipoproteins via downregulation of Erk-5/Mef2c/KLF2 signaling: Amelioration by Fisetin.

 

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

 

Nicotinamide phosphoribosyltransferase postpones rat bone marrow mesenchymal stem cell senescence by mediating NAD+-Sirt1 signaling. Full Text

 

Nicotinamide Riboside (NR) – NAD+ precursor.

 

Role of mitochondria in diabetic peripheral neuropathy: Influencing the NAD+-dependent SIRT1-PGC-1α-TFAM pathway. Full Text
Nicotinamide Riboside, an NAD + Precursor, Reduces Hepatic Stellate Cell Activation and Attenuates Liver Fibrosis in a Diet-induced Mouse Model of Liver Fibrosis 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.

 

Stilbene Compounds Inhibit Tumor Growth by the Induction of Cellular Senescence and the Inhibition of Telomerase Activity. Full Text
Pterostilbene reverses palmitic acid mediated insulin resistance in HepG2 cells by reducing oxidative stress and triglyceride accumulation.

 

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.

 

The impact of resveratrol on toxicity and related complications of advanced glycation end products: A systematic review.
*Higher Dietary Intake of Resveratrol Was Associated with Lower Risk of Hip Fracture- a 1:1 Matched Case-control Study in Chinese Elderly Full Text

 

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.

 

Prescription Supplements

 

Rapamycin (sirolimus) – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer. Taking 5mg once a week.

 

Stimulation of Hair Growth by Small Molecules that Activate Autophagy Full Text
Effect of sirolimus on coagulopathy of slow-flow vascular malformations
The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with lymphatic anomalies Full Text
Protective effects of rapamycin induced autophagy on CLP septic mice.
Rapamycin Affects Palmitate-Induced Lipotoxicity in Osteoblasts by Modulating Apoptosis and Autophagy.
mTOR and Aging: An Old Fashioned Dress (Rapamycin Review) Full Text
Deregulated MTOR (mechanistic target of rapamycin kinase) is responsible for autophagy defects exacerbating kidney stone development.
Longevity-related molecular pathways are subject to midlife "switch" in humans. 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:

 

Cellular senescence in cardiac diseases. Full Text
Knockdown of angiopoietin-like 2 induces clearance of vascular endothelial senescent cells by apoptosis, promotes endothelial repair and slows atherogenesis in mice. Full Text
Slug Saves Satellite Cells from Senescence Full Text
NAD+ and Cellular Senescence Pathways Interact
Directed elimination of senescent cells attenuates development of osteoarthritis by inhibition of c-IAP and XIAP.