The body is a complex machine.

Like any machine, it wears down over time during its normal course of operations.

This is a process of decay and accumulation of damage, so combating aging is simply a technical repair and maintenance problem.

There are various types of damage that the body does to itself as a side effect of the way the body works. Damage is always happening, and right now there is only so much that we can do to minimize that rate, and there’s only so much accumulated damage that we can tolerate. But our work revolves around repairing that ongoing damage. It’s just like a car. As carefully as we drive it and as diligently as we keep it oiled, sooner or later the engine will give out and it will stop running. But if a mechanic keeps replacing the broken parts, it can last forever. Vintage cars were not designed to last more than ten or 15 years, but preventive maintenance, so long as it’s comprehensive, can completely transcend any such limits. – Aubrey de Grey, SENS Research Foundation

Our bodies are a bit like a house, we inhabit them, and if you don’t maintain the house it’s not going to last for very long, and if you do maintain the house it can last indefinitely. There are some houses that are thousands of years old. The only difference between a house and this house I inhabit is we understand how a house works because we built it. We don’t fully understand this house yet. But that understanding is increasing exponentially. – Ray Kurzweil

100,000 people die every day because the human body currently has insufficient methods of dealing with the cellular and molecular damage that accumulates over time.

Strategies are needed to intervene and repair this damage to keep the body maintained at a level below the threshold where problems start to occur.

THE GOAL: BRIDGE 1 ——> BRIDGE 2

Bridge 1 – What You Can Do Now to Live Long Enough to Get to Bridge 2

This stage involves using existing strategies to delay the buildup of damage in order to prolong your current life expectancy as much possible.

The most obvious options for achieving this are lifestyle approaches such as optimizing sleep, exercise, food, and stress levels.

Blue Zone research details lifestyle commonalities that communities with high life expectancies share. The top 5 places are:

Sardinia (Italy)

Okinawa (Japan)

Loma Linda (USA)

Nicoya Peninsula (Costa Rica)

Icaria (Greece)

Specific health and anti-aging supplements are also a possible option for slowing the damage that the process of aging wreaks on the body.

The effectiveness of these existing options are unfortunately dubious and speculative. A healthy lifestyle will certainly improve your quality of life but can’t work miracles in extending your life. It may win you anywhere from a few more years to a decade at most.

For example, compare the difference in life expectancy between Japan and the US. It’s only 4 years despite Japan being number 1 in the world and America being way down in 31st.

Loma Linda, California has the longest life expectancy in North America due to dietary and lifestyle habits. The vast majority of the population are Seventh-day Adventists. On average Adventist men live 7.3 years longer than other Californians.

An extra 4-7 years gained from a better lifestyle doesn’t sound like a lot, but it could be the difference between being around or not when the technology emerges that can buy you an extra 30 years.

Given the inadequacy of current methods to extend life dramatically, the whole point of Bridge 1 is just to live long enough to get to Bridge 2 in relatively good shape.

2020s / 2030s

Bridge 2: The Biotech Revolution

Ray Kurzweil’s Forecast: 2020’s

Aubrey de Grey’s Forecast: Mid 2020s

The next decade will be the most exciting in the history of biological sciences. – Craig Venter

This is the biotech era. In some ways it has already begun, think stem cells and CRISPR, but is not yet widely deployed. The biotech revolution is expected to bear fruit in the 2020s and 2030s.

As the biotech industry matures, we will have access to far more powerful methods than we currently do to reprogram our genes away from aging and disease.

A key turning point in the fight against aging is when cellular and molecular therapies have advanced to the stage that we can double or triple the lifespan of mice (at the moment we can manage 40%).

This is what Aubrey de Grey calls “Robust Mouse Rejuvenation” and he expects it to shake people out of their “pro-aging trance” as it will show without doubt that aging can be conquered.

He believes this will start an era of massive funding as people demand similar anti-aging treatments for humans.

2030s / 2040s

Life Extension Escape Velocity

Ray Kurzweil’s Forecast: 2029

Aubrey de Grey’s Forecast: Late 2030s / Early 2040s

This is when biotech (and ultimately nanotech) has matured to the extent that therapies and treatments are now good enough to maintain the damage accumulated in the body at a safe level indefinitely.

Ray Kurzweil describes this as when we have the means to extend your remaining life expectancy by an additional 1 year, every year that passes.

At this stage aging will be a solved problem.

RAY KURZWEIL’S BRIDGE 1 STRATEGY

One of the most aggressive approaches to surviving Bridge 1 is Ray Kurzweil’s supplement regime.

In 2012 Ray stated that he takes about 150 pills per day (which is 70-80 different things) as part of his quest to get to “Bridge 2”.

By 2015 he had managed to get this down to 100 pills per day by finding more bio-available forms.

This costs him a few thousand dollars per year, although he says it’s not necessary for everyone. “It’s not one size fits all. A healthy 30-year-old might just need basic supplements”.

Kurzweil has been accused of being “reckless” with his level of supplementation, which he refutes:

I monitor my body regularly. I’m not just flying without instrumentation. Being an engineer, I like data and I monitor 50 or 60 different blood levels every few months, and I’m constantly fine-tuning my program. All of my blood levels are ideal. I scan my arteries to see if I have plaque buildup, and I have no atherosclerosis. I come out younger on biological aging tests. So far, so good. But this program is not designed to last a very long time. This program is what we call bridge one. The goal is to get to bridge two: the biotechnology revolution, where we can reprogram biology away from disease.

Below is a list of some of the supplements Ray has previously mentioned taking:

For Anti-Oxidation and General Health

Comprehensive multi-vitamin

Coenzyme Q10

Grapeseed extract

Resveratrol

Bilberry extract

Lycopene

Silymarin

Linoleic acid

Lecithin

N-acetyl-cysteine

Garlic

L-carnitine

Pyrodoxal-5-phosphate:

Echinacea

B12 shots

For LDL and HDL Levels

Policosanol

Gugulipid

Plant sterols

Niacin

Oat bran

Grapefruit powder

Psyllium

Lecithin

Lipitor

For Blood-Vessel Health

Arginine

TMG

Choline

To Lower Blood Viscosity

Aspirin

Lumbrokinase

To Reduce Inflammation

EPA/DHA

Curcumin

To Reduce Homocysteine Levels

Folic acid

B6

For Detoxification

EDTA

DMPS

For the Liver

Intravenous glutathione

For Cell Membranes

Intravenous phosphatidylcholine

For Testosterone Levels

PtC

DHEA

Testosterone

l-3-C

Chrysin

Nettle

Ginger

For the Prostate

Saw palmetto complex

For Stress

L-theanine

Beta-sitosterol

Phosphatidylserine

Green tea extract

For the Brain

GABA

Melatonin

Glycerylphosphatidylcholine

Nextrutine

Quercetin

For the Eyes

Lutein

Bilberry extract

For the Skin

Antioxidant skin creams

For Digestion

Betaine HCL

Pepsin

Gentian root

Peppermint

Acidophilus bifodobacter

Fructooligosaccharides

Fish proteins

L-glutamine

N-acetyl-d-glucosamine

To Inhibit Glycosylated End Products

N-acetyl-carnitine

Carnosine

Quercetin

Alpha lipoic acid

ANALYSIS OF NOTABLE BRIDGE 1 LONGEVITY OPTIONS

VITAMINS

Vitamin D

This is one of Ray Kurzweil’s Top 3 Supplements for Surviving to the Singularity.

He claims it is the most important vitamin to take and that there is tremendous amounts of research and consensus that it helps prevent cancer and other diseases.

Most people are deficient in vitamin D.

The latest news and research is best found at the Vitamin D Council’s website.

ANTIOXIDANTS & GENERAL HEALTH

Spirulina

Spirulina algae is an antioxidant.

It is regarded as the most nutrient-dense food in the world.

FOR THE CELL MEMBRANE

Phosphatidylcholine

90% of the cell membrane in a 10 year old is made up of a substance called Phosphatidylcholine.

This depletes over time and the membrane gets filled in with inert substances like cholesterol and heart fats. By the time you’re 90 it’s down to 10%.

This is a major aging problem and is why the skin in an elderly person sags and organs don’t work very well.

The process can be alleviated by supplementing with Phosphatidylcholine.

It is one of Ray Kurzweil’s top 3 supplements for surviving to the Singularity.

Kurzweil says the best way to take it is intravenously to get it right into the blood stream where it can be delivered to the cells (every week he has an I.V). He also takes it every day orally and says this does a fairly good job.

More information about supplementing with Phosphatidylcholine can be found here.

FOR THE CELL’S MITOCHONDRIA

Coenzyme Q10

Mitochondria are responsible for energy production in our cells. Coenzyme Q10 is a part of this energy generation.

Disruption to the mitochondria is a major part of the aging process and this supplement is claimed to help slow that down.

Coenzyme Q10 is an antioxidant that lowers blood pressure and protects the heart.

It is one of Ray Kurzweil’s top 3 supplements for surviving to the Singularity.

Nicotinamide Adenine Dinucleotide (NAD+)

As mentioned above, damage to mitochondria accumulates over the years and is one of the main contributors to the negative effects of aging.

NAD+ is a coenzyme in cells. Boosting NAD+ levels has been shown to dramatically reverse the aging of mitochondria in mice cells. A 2013 experiment demonstrating this was hailed as a key breakthrough and became the focus of widespread media attention.

The two most well-known NAD+ supplements currently on the market are:

1) Niagen

Niagen contains nicotinamide riboside (NR) which boosts NAD levels.

Niagen is manufactured by Californian company ChromaDex and is available to buy under various brand names.

ChromaDex claim that a human clinical trial confirmed that NR Increases NAD+ and is safe.

This study is currently being peer reviewed (results expected in late 2016) and the company is hoping to win FDA approval.

2) Basis

The NR supplement Basis is produced by high profile start up Elysium and has made headlines as an anti-aging pill. Elysium is associated with noble prize winners and biotech pioneers.

The pill also contains Pterostilbene, a compound commonly referred to as a stronger version of resveratrol

Basis is available to buy from Elysium’s website for $60 (30-day supply) or $50 a month (ongoing subscription).

CALORIE RESTRICTION MIMETICS

Resveratrol

Resveratrol is perhaps the most famous antioxidant with perceived longevity benefits due to its presence in red wine.

It’s thought that resveratrol may help maintain DNA, protect cells, and supporting mitochondrial function.

Health and longevity improvements have been observed in mice and it’s possible that these carry over to humans. However, clinical evidence of its benefits is lacking, although research is ongoing.

Along with Metformin and Rapamycin, it is a known calorie restrictive mimetic which is thought to extend life by tricking the body into believing it’s running out of energy. This causes it to put more effort into long-term survival.

Supplementing resveratrol may be beneficial but better results need to be demonstrated.

Pterostilbene

Pterostilbene is nearly identical to resveratrol but is considered to be more potent.

It is a natural dietary compound and the primary antioxidant component of blueberries.

It’s also claimed to be significantly more bio-available than resveratrol so is better absorbed by the body.

The benefits of pterostilbene have not yet been proven in clinical trials but preliminary studies are ongoing and reportedly promising.

It may be too early to start using it as a regular supplement, but it’s more interesting than resveratrol and the potential benefits make it worth keeping an eye on as more information becomes available.

Rapamycin

Rapamycin extends lifespan in mice. It works by blocking the protein TOR (Target of Rapamycin). It is currently being tested on dogs.

Rapamycin is a known calorie restrictive mimetic.

Unfortunately, it has nasty side effects. More work needs to be done to develop rapamycin into a safe drug for humans.

Dave Harrison, team member of a study of rapamycin on mice, said “It may do more harm than good {for humans], as we know neither optimal doses nor schedules of when to start for anti-ageing effects.”

Metformin

Metformin releases more oxygen into cells, which is believed to result in longevity benefits.

It is a calorie restriction mimetic.

Calorie restriction is proven to extend the lives of a variety of organisms from yeast cells to monkeys. Metformin activates this response without us having to go through the ordeal of starving ourselves.

Metformin has extended the lives of lab mice by as much as 40% but unfortunately this doesn’t mean it will translate to a 40% increase in human life expectancy. It just doesn’t scale like that.

Aubrey de Grey believes that life extension gains in nominal years for humans will be limited because calorie restriction has considerably less benefits proportionally in long lived species than short lived species.

Upcoming Metformin FDA Trials known as TAME (Targeting Aging with Metformin) will be conducted on 3,000 people aged 70 to 80.

This trial is a milestone, as for the first time ever, the FDA are engaging in anti-aging medicine.

Up until now, the FDA has refused to engage with attempts to treat aging. This has been very damaging as it’s had a chilling effect on the medical community’s interest in developing drugs.

Metformin is commonly available and has been around for a long time (it was invented in 1959). It is very cheap at around 6 cents per pill. Some people experience side effects but on balance these are considered relatively minimal.

Overall, Metformin’s positive impact is likely to be a few years of life extension at best, but it still might be a good option until more powerful alternatives become available as we approach Bridge 2 in the 2020s and 2030s.

The FDA trials start this year. Results and a recommended course of action will become more apparent in 5 or 6 years when we can see if it helped delay death and prevent diseases.

TELOMERE LENGTHENING

TA-65

Telomeres are protective caps on the end of chromosomes.

Each time a cell divides the telomeres become shorter. When they get too short, the cell can no longer divide.

At this point the cell becomes inactive (senescent) or it dies. This is associated with both aging and disease.

The theory is to increase levels of the enzyme Telomerase which prevents the telomeres from shortening.

TA-65 is a drug which is claimed to increase telomerase, but results so far are mixed and peer reviewed studies are lacking.

The goal of maintaining telomere length to increase life expectancy is controversial due to its association with cancer.

Cancer cells produce telomerase which enables them to prevent telomere shortening. Unfortunately this enables the cancer cells to divide uncontrollably and wreak havoc.

Overall, it’s possible that increasing telomerase in the body is misguided and will do more harm than good.

ADVANCED METHODS

Stem Cell Therapy

Most of the most important breakthroughs in the past decade have been preliminary. They have been early-stage work but have not yet reached the clinic. So, one example is induced pluripotency, the ability to take cells and reverse their development, to take them back to a stage that we normally, naturally see only shortly after fertilization. That is enormously important, because it allows us to create cells that are of any kind we like, more or less. And that we can reintroduce into that same person. That’s hugely important for sidestepping the problem of immune rejection that exists if you try to put cells from one person into another person. – Aubrey de Grey

In just the last 10 years there has been more progress than many researchers thought they’d see in their lifetimes. Where we go in the next 20 years is going to be very interesting to say the least.

One of the major causes of damage during aging is loss of cells. A promising approach to solving this is to use stem cells to restore and replace these cells and tissues.

Stem cell therapy is a still at an early stage of development so it’s far too early for most people to get involved in the therapies that are currently available.

Further breakthroughs in stem cell therapy should be watched closely in the years ahead as we progress towards Bridge 2

Gene Therapy

Gene therapy involves manipulating DNA to prevent damaging processes from occurring. It’s been around for a while but previous techniques were unreliable and risky.

CRISPR-Cas9 is a newer and much more accurate tool to cut and edit DNA.

CRISPR is considered one of the biggest breakthroughs in history. Research is moving fast and we are seeing big improvements in its application. For example, using the protein Cpf1 instead of Cas9 has already been shown to result in a much better outcome.

CRISPR human trials are due to commence next month at Sichuan University’s West China hospital in Chengdu, China.

In America, the CEO of biotech startup BioViva recently made headlines by claiming that she is the first person to be successfully rejuvenated by gene therapy.

This claim is extremely dubious and results haven’t been submitted for peer-reviewed publication, but it’s another indication of how close we are to the biotech revolution (Bridge 2) and what will soon be possible.

Gene editing is inevitable and is by far our best chance of getting a grip on the damage aging brings. It’s just a matter of time.

REVIEW OF NOTABLE BRIDGE 1 LONGEVITY OPTIONS

Unfortunately benefits from existing supplements are likely to be minimal, although some are intriguing enough to be worth proceeding with depending on a person’s current profile.

Gene and cell therapy are the big hopes. These exist today in nascent form but need to mature if we are to enjoy life extension of multiple decades rather than the few years that can be currently gained.

Some of the most ambitious and intriguing work for achieving this is being done by the SENS Research Foundation who have been awarded multi-million dollar donations from Peter Thiel and entrepreneur Michael Greve.

SENS also crowdfunds specific projects and accepts bitcoin. Keep up to date with the latest news and developments at sens.org

CONCLUSION: BRIDGE 1 ANTI-AGING STRATEGIES

BEST OF THE CURRENT BUNCH

VITAMINS

Vitamin D

ANTIOXIDNTS & GENERAL HEALTH

Spirulina

MAINTAINANCE OF THE CELL’S MITOCHONDRIA

Coenzyme Q10

MAINTAINANCE OF THE CELL MEMBRANE

Phosphatidylcholine

ONES TO WATCH (MOST PROMISING)

Near – Medium Term

Pterostilbene

Nicotinamide Riboside (NAD+)

Metformin

Medium – Long Term

Stem Cell Therapy

Gene Therapy

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