January 2019 Longevity Review

Introduction

Firstly, if you haven’t backed up your hard drive recently – do it NOW! A few weeks ago I lost all my music & scientific paper downloads from the past year (fortunately I did back up all my photos/videos).
Now that you’ve backed up your hard drive…

To start with, a bit of an introduction to these monthly email updates. I have taken on-board the advice that you do not want to be wading through lengthy emails, so I have divided it into 3 parts.

The first part will be brief descriptions and internet links to a handful of longevity highlights from the past month. The second will be a link to a video or podcast, not necessarily from the past month, which will bring more in-depth insights into a facet of this field. The third part, which is attached as a Word Document, is where you need to put your waders on! Here, I will be delving into the world of supplements and drugs available to take now. This will eventually morph into a supplement guide, but for now, it mainly consists of links to last month’s research into my favourite supplements. It is lengthy however!

Please let me know what you think about this format, or if there is anything that you would like included.
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January Round-up

• The most important and exciting news of the past month was the completion of the first human senolytic’s trial. Senolytics clear out senescent or “zombie cells”, which cause dysfunction, and their clearance partially rejuvenates old tissue. This first trial was a safety study in Idiopathic Pulmonary Fibrosis (a fatal lung disease) using a combination of Dasatinib (a cancer drug) & Quercetin (a food supplement). As it only had 14 patients and was of short duration, no conclusions can be drawn; however, it was safe and some overall health markers improved. Larger follow up studies are planned. Further such studies should hopefully be released later this year, giving some indication if the amazing results in animals can be replicated in humans.

• There is a search under way to discover factors in young blood which could make you younger (see GDF11 below). The latest such factor to promote rejuvenation, especially that of the liver, was discovered last month:

• For research in ageing to speed-up, we need to be able to accurately judge biological age, otherwise any human lifespan studies would take decades. Fortunately, scientists have been working on such ageing “clocks” and the most advanced yet, which can supposedly show how much longer you have left to live, was released last month:

• One of my biggest bugbears in ageing research has been the fact that interventions are usually applied individually, whereas they need to be combined as ageing is so multifactorial. In this paper researchers have combined pairs of six plant-extracts (Black Cohosh, Valerian, Purple Passionflower, Ginkgo Biloba, Celeriac & White Willow) to see if they could synergistically extend the lifespan of yeast, which they successfully accomplished:

• The Interventions Testing Program (ITP), run by the US government, has been the gold standard in longevity interventions in mice. They were the first to show that Rapamycin lengthens rodent lives. Its latest paper, shows that Acarbose (a diabetes medication) also extends the lifespan of mice:

• While most people have heard of stem cells, most people don’t realize that their creation from adult tissue involves the cells being rejuvenated to a more youthful state. If the same could be done to whole animals instead of cells, then true rejuvenation would be at hand. The paper below is now the 3rd time this is being attempted, in this instance to speed up the healing of muscle injury in mice:

GDF11 – A young blood factor

As mentioned above, there​ is an ongoing search for factors in young blood which might be able to rejuvenate an older organism. The first such factor, GDF11, was discovered and caused much excitement back in 2014 by seeming to rejuvenate older mice. Since then there has been some controversy, with some scientists contesting the early results, but recently the science seems to be swinging back in its favour. However, before the science was in any way settled, one brave (crazy?) soul decided to experiment on himself and began injecting GDF11. After some initial issues, he reported some remarkable results and in the intervening four years has had over a hundred people join him. What makes this individual stand out from the usual motley of hucksters, is his insistence on fastidiously recording biomarkers, which he shares freely on his website. This transparency, as well as the fact that he’s not trying to sell the product, makes him and his results more believable. However, although very interesting, this research is still in its infancy and I would not suggest anyone trying out GDF11 themselves. I am keeping a close eye on it though. Check out the video presentation below:

Steve Perry’s Raadfest Presentation:

GDF11 Website, where all the biomarker data can be found: https://gdf11rejuvenation.com/

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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

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Supplemental Information

Supplemental Introduction – Until recently, I had not paid too much attention to supplements, thinking them to be ineffectual, while focusing on longer term and more effective anti-ageing science/solutions. I thought that a healthy lifestyle was the best one could do presently. However, upon entering my 40s and noticing the ever increasing signs of ageing staring back at me, I have reappraised my thinking.

Now, there are countless numbers of supplements out there, most of which spout some miraculous claim or another, and I don’t have the time nor inclination to research them all. Only those which have some scientific backing, and thus have appeared in my science sites, have caught my attention. Therefore, the list below is by no means exhaustive. I’m sure that there must be some beneficial supplements which I am currently ignoring, but will pick up on once an important paper comes out – as the recent example of Fisetin for me shows.
You’ll notice that the formatting changes between the supplements, either giving the title of the scientific paper or just the disease/condition affected. Please let me know which format you prefer as well as if the information below is useful. My hunch is that it is a bit unwieldy at the moment, but I hope to improve on that with future updates.

**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. Here is some scientific evidence of the molecular changes driving the beneficial effects:
Fasting speeds up metabolism & increases healthy metabolites Article

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.
Inflammatory bowel disease PMC
Efficacy of high-affinity liposomal astaxanthin on up-regulation of age-related markers induced by oxidative stress in human corneal epithelial cells. PMC
Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK PMC
Astaxanthin but not quercetin preserves mitochondrial integrity and function, ameliorates oxidative stress, and reduces heat-induced skeletal muscle injury
Protective effects of astaxanthin on subarachnoid hemorrhage-induced early brain injury: Reduction of cerebral vasospasm and improvement of neuron survival and mitochondrial function
Astaxanthin mitigates subarachnoid hemorrhage injury primarily by increasing sirtuin 1 and inhibiting the Toll-like receptor 4 signaling pathway
Astaxanthin enhances the longevity of Saccharomyces cerevisiae (yeast) by decreasing oxidative stress and apoptosis.

Curcumin – the spice which gives curries their yellow colour. Anti-inflammatory and neuroprotective. I take 1 gram a day.
Effect of curcumin on memory impairment: A systematic review.
Curcumin prevents cigarette smoke extract induced cognitive impairment.
*Does turmeric/curcumin supplementation improve serum alanine aminotransferase and aspartate aminotransferase levels in patients with nonalcoholic fatty liver disease? A systematic review and meta-analysis of randomized controlled trials.
Curcumin reduces inflammation in knee osteoarthritis rats through blocking TLR4 /MyD88/NF-κB signal pathway.

Fisetin – a flavonoid found in highest concentration in strawberries. Senolytic, anti-inflammatory, neuro-protective & Sir1 activator. I newly take 100mg daily.
Fisetin, a potential caloric restriction mimetic, attenuates senescence biomarkers in rat erythrocytes

Nicotinamide MonoNucleotide (NMN) – newer NAD+ precursor. I take 250mg daily.
There was a lot of debate about whether NMN can enter cells on its own, or if it needed to be converted first to NR. That debate has been settled by the following paper:
NMN Enters Cells via Newly Discovered Pathway Full Paper
Neuroprotection
Aluminium Induced Bone Loss
Intestinal Ageing
Therapeutic Applications

Nicotinamide Riboside (NR) – NAD+ precursor.
Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring.

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.
Fructose Induced Liver Fibrosis
Anti-depressant
Renal Fibrosis(1) (2)
Acetaminophen-induced liver injury

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.
Resveratrol: Twenty Years of Growth, Development and Controversy.
*Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial.
A Review of Resveratrol as a Potent Chemoprotective and Synergistic Agent in Cancer Chemotherapy. Article
The Effects of Resveratrol in the Treatment of Metabolic Syndrome. Article

Spermidine – found in wheat germ and a potent inducer of autophagy. Try to eat a couple of tablespoons of wheat germ every day.
Pairwise combinations of chemical compounds that delay yeast chronological aging through different signaling pathways display synergistic effects on the extent of aging delay PMC
Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans? PMC

Prescription Supplements

Rapamycin – first drug proven to increase the health & lifespan of mice. Currently used for organ transplantation and against cancer. My order has arrived, it’s sitting in the fridge and I’m going to start taking it soon.
Testicular injury
Urinary Disease
Subarachnoid Hemorrhage
Alzheimer’s Trial
Atherosclerosis
Osteoporosis

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:
UNITY Biotechnologies Selects a New Senolytic Candidate
The curcumin analog EF24 is a novel senolytic agent