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Lifespan

Lifespan by David Sinclair is an awesome book about how we can extend lifespan and the implication. Optimism abounds with Sinclair, but his research does keep him somewhat to the ground.

For many later parts in the book (the speculative/extrapolations) it’s difficult for me to judge where we’re going. But I dearly hope that he is right and that we will be living much longer than our parents.

And yes, that is healthspan, not only lifespan. Or in other words, I want to live in a healthy body, not extend the last phase forever.

At a later date, I will write down more extensive notes (when the longevity theme – 2020 goals – comes around).

Here is another good summary.

Eight Weeks to Optimum Health

Eight Weeks to Optimum Health by Andrew Weil was not my cup of green tea. I think the biggest problem was that his information is based on outdated science and many anecdotes. So although he is coming from the right place, I couldn’t agree with many of the specifics.

I can say that his advice is much better than the average American diet. It also does do a good job of seeing food as part of something larger and includes things like meditation. It’s more holistic than how we normally look at diet.

Some more notes:

  • Dietary advice includes the following: Brocolli, fish or flax, fruits and vegetables (organic – although that also loses some of it’s meaning nowadays), soy foods, whole grains, cooked greens, garlic and ginger
  • Antioxidants (but as far as I know the evidence is fleeting for them)
    • And he mentions quite a lot of supplements to take. At the same time I’m contemplating some supplements (vit D, B12), so it does make some sense
  • Walk and stretch (good advice)
  • I didn’t like his definition of spontaneous healing, it’s just our body doing it’s thing – nothing special about it or that it will be activated by X, Y, or Z. And yes we can sometimes beat cancer without a doctors interventions, but that doesn’t mean it should be the way to go.
  • The book relies on testimony – way too much
  • “… which gave me a means to access cellular memory” – WTF

Juvenescence

Juvenescence by Jim Mellon and Al Chalabi is a book aimed squarely at investors who want to invest in the new hot thing and get better than average returns. I personally am not on board with the long-term ability of people/groups/investors to do this (A Random Walk Down Wall Street), but at the same time I’m very interested in the field and this book provides a good helicopter view of the possibilities.

Here is a compressed index of the book:

  • What is ageing and can it be slowed, reversed or eliminated?
  • Multiple theories of ageing
  • Five deadly diseases (of ageing)
  • Animal models (research models)
  • Key opinion leaders
  • Target therapies
  • Life expectancy and demographics
  • Companies (to invest in)
  • What you can do yourself to stay healthy/young

Greg Bailey (investor and entrepreneur) gives an introduction to the book. He argues that we’re at a breakthrough moment in ageing research. Where first the focus was on lifestyle interventions (adding a few healthy years, possibly even extending lifespan a bit), it’s now on drugs/therapies that might extend life by much more. He argues that inflammation and insulin resistance are most probably two mechanisms that have much to do with how we age (but the evidence isn’t clear yet how the causal effects work). He personally takes metformin, a statin, baby aspirin, with fish oil, curcumin, vitamin D and B, nicotinamide mononucleotide (NMN) and episodic calcium.

Longevity is taking flight, just as flight was some 100 years ago. Two key issues are:

  1. How to cure or tame diseases that become more prevalent and devastating as people age
  2. How to research ageing as a unitary disease in itself

To do this, we must look at the cells itself, an area that is now exploding (with investment and discoveries). It’s also relatively recently that more and more researches have begun to see ageing as a disease. Before, and still for many people, the separate diseases are treated as such. The effects of a longer healthy lifespan will result in lower health costs, more productivity and economic growth.

Definition: Ageing is marked by a progressive loss of physical integrity, with lessened functionality and increased vulnerability to death.

The Human Cell Atlas aims to identify every cell in every tissue (about 37 trillion in total).

What is Ageing and can it be Slowed, Reversed or Eliminated?

“The short answers: it’s bad, maybe, possibly, and probably not!”

The goal of most researchers is to extend healthy lifespan, to have a very short period of illness. Most current therapies are focussed on this, only soon will we also be able to (radically) extend lifespan in general. The current ‘hard’ ceiling proposed in the book is 115 years. They speak of a bridge being built, one that connects/makes us survive until we find the ‘real/long-term’ solutions.

One change in attitudes is that we can see ageing as a single disease complex. Regenerative medicine will allow us to restore our bodies to the best/optimal state. Thus we should focus on the causes of ageing (e.g. chronic inflammation, cell breakdown, mitochondrial DNA damage, stem cell depletion, cellular senescence).

The authors speak about why it’s now the right time to invest. They argue that genomic sequencing, the imminent appearance of therapies make this the right moment.

Human research takes very long (we don’t die quickly) and is very expensive. Yeast, worms, and mice models are sometimes good proxies (and the best we have now).

“Already, we can, and are, reducing the risk of dying from the diseases of ageing. For instance, cardiovascular disease (CVD) related deaths and cancer deaths are each falling in developed countries by about 2 to 4% per annum.

“Ageing is rigorously described as senescence, the progressive degradation of bodily functions.”

Changes/mutation at the beginning of life may help us, but be detrimental later in life (Medawar-Williams Theory).

“Molecules become unbound, genes become inefficient, waste products (cellular debris) build up… shortening of telomeres, reduced mitochondrial function (limiting energy production), the depletion of the potency of stem cells, and impaired cellular networks.”

For now there are no specifically approved or recommended treatments to delay or to reverse ageing, other than [caloric restriction/lifestyle changes]”

Yet they are optimistic because we are starting to understand more and more.

The mitochondria, large structures (‘organelles’) within our cells, are the machines that extract energy from nutrients and store it as adenosine triphosphate (ATP).” With age, they become less effective.

The immune system also becomes less effective (immunosenescence). And other things break down (we get cancer, lose hair, lose balance, type 2 diabetes, etc).

Some types of cells are immortal (e.g. cancer cells). But many of our cells don’t do well at copying after 50 times (too many mistakes). This has been called the Hayflick Limit.

Twin-studies showed that only 20% of date of death was genetic, 80% was environment (not clear how much is (bad)luck and how much is smoking, diet, sleep, etc).

Because of attacks from outside the body (exogenous) and inside (endogenous), we can’t expect our bodies to stay the same (homeostasis). I think that Aubrey de Grey tries to argue that we should make our repair systems so good as to do maintain this. One other aspect to take into account is oxidative stress (reactive oxygen species, ROS). This also increases over time as those free radicals damage cells.

You should be able to estimate your biological age with an epigenetic clock (Horvath, et al.)

“Though we must again stress that our estimates of timeframes are immensely speculative… average life expectancy… will rise from about 73 today to lose to 100 (in 20 years)” … “That said, if you can stay alive for another ten to twenty years, and if you aren’t yet over 75, and if you remain in reasonable health for your age, you have an excellent chance of living to over 110 years old.”

Inflammaging and the declining immune system

“[Inflammaging] describe[s] the aspects of the breakdown of intercellular communication and the gradual failure of the immune system.”

When the innate and learned/adaptive systems begin to fail (called immunosenescence), your body can’t fight infections anymore. In parallel, the immune system is fighting battles it can’t win, leading to persistent inflammation (inflammaging).

In your guts is where most of this happens, this is where your microbiome is (many bacteria). Specifically, the NLRP3 gene (which encodes the cryopyrin protein) becomes less effective.

The B-cells (from bone marrow) and T-cells (ditto, and thymus) also slows with ageing. There are also less ‘naive’ ones, that are open to learning to fight new pathogens. “Immunosurvelliance of persistent viruses and in particular of the cytomegalovirus (CMS), causes stress to T-cells.”

They mention that inflammaging is linked to the big killers. And that resveratrol and metformin might have pathways to suppress/dampen inflammaging.

Growth hormones might also help here (IGF-1) and FGF7. Yet the former is also mentioned elsewhere as a possible negative influence.

Another avenue is to improve our (gut) microbiome. One theory is that in older people the relationship moves from symbiotic to hostile.

Theories of Ageing (views converging)

“… ageing is currently inescapable, that it is characterised by the progressive loss of functioning of our bodies and that it is the principal cause of [deaths from cardiac diseases, cancer, etc].”

The two (broad) views are that 1) ageing is preprogrammed in a way, and 2) that it’s random/stochastic. The former says that there is something in our cells that triggers at some programmed time. The latter says that accumulation of damage, free radicals, etc just heap up over time.

The hallmarks of ageing are (López-Otín, Carlos, et al.)

  • Genomic instability
  • Telomere attrition
  • Epigenetic alterations
  • Loss of proteostasis
  • Deregulated nutrient sensing
  • Mitochondrial dysfunctioning
  • Cellular senescence
  • Stem cell exhaustion

Proteostasis

This is the loss of homeostasis in the proteome (protein 100-250k we need for life). Proteostasis involves cleaning up misfolded proteins. When this doesn’t happen effectively anymore, diseases start to develop.

Chaperone molecules are proteins (or drugs) that refold misshapen proteins. Two systems are used by the body to destroy misfolded proteins (autophagy-lysosmal and ubiquitin-proteasome systems).

Too many unfolded/misfolded/clumped proteins are implicated in (causing?) Parkinson’s and Alzheimer’s (Powers, et al. 2009).

Boosting proteostasis might increase longevity.


Phenotypes refer to the physical and behavioural expression of genotypes. You get the latter from your parents, the former is influenced by your environment. Natural selection might select for the ones that reproduce earlier (since they have kids that have their genes), of course this is offset by the chance of those kids surviving. (more is said about evolution and why for instance reptiles don’t seem to age that quick/are still fit at an older age). They also use the example of eunuchs (no chance of reproduction), but not everywhere they lived longer.

Most scientists don’t evoke the second law of thermodynamics (entropy) when talking about ageing. Leonard Hayflick does, and so does Peter Hoffman. Aubrey de Grey argues that people are very good at combatting entropy, but that we should help our cells repair mechanisms.

The disposable soma (body) theory states that ageing occurs due to the accumulation of damage during life. This view argues that we die some time after our ‘usefulness period’ (passing on genes) but leaves the door open to doing repairs etc after that. One correct prediction that it makes, is that in times of low calories, people survive longer (and have fewer kids).

Free radicals, DNA damage and the oxidative theory of ageing states that those three are responsible for ageing. Antioxidants (as applied now) don’t show consistent positive effects. Too much unrepaired DNA does show to change the chromatin (what chromosomes are made of). Caloric restriction (CR) might help a bit (but not much).

The theory of antagonistic pleiotropy argues that a gene variant is beneficial to our survival in early life, becomes harmful as we age. Another view is that ageing does stop at very old ages (and people die of exhaustion?).

The hyperfunction theory argues that the ‘hyperfunction’ of things useful in youth are also causes of ageing/death. Excessive signalling of mTOR and insulin/IGF-1 are examples of this.

The rate of living theory says that the slower the metabolism, the longer an organism lives (Kleiber’s Law).

Most theories contain a piece of the truth. Yet we don’t know at this moment which is best/what is to come (otherwise we would already have solved ageing).

DNA Damage

DNA damage occurs through free radicals (ROS). This happens about 10.000 times per day in humans, in every cell! And one repair takes 10.000 molecules of ATP to repair. (so if my math is correct, 100 million ATP molecules per cell. We have 37 trillion cells, so 3.7e+21 ATP molecules get to work every day. Lol, numbers were calculated in the book too, we have only 50grams of ATP, it’s recycled so fast, we use 180kg per day (overturned)).

“Unrepaired DNA damage is particularly noticeable in non-dividing or slowly dividing cells, such as neuronal, heart and skeletal cells because the mutations tend to persist. Whereas in dividing cells, such as those of the liver, DNA damage that is not repaired will normally automatically induce cell death, though occasionally it can lead to the development of aberrant cancerous cells.”

“ATP liberates energy by being converted into ADP (adenosine diphospahte), by removing one of the phosphate groups. ATP becomes spent when it is converted to ADP. The ADP group is then recycled in the mitochondria, recharged, and re-emerges as ATP and the cycle continues.”

More nuclear DNA damage over time means a greater risk of cancer (which happens with age).

Some (SENS) argue that mitochondrial DNA (mtDNA) mutations in slowly dividing cells are causative of ageing.

The Deadly Quintet

Cardiovascular diseases

Deaths from cardiovascular diseases (CVD) are falling worldwide. In the US this is 20% in the last 20 years (per capita). LDL (bad cholesterol) is a major factor in the formation of heart diseases. Statins (David Sinclair also argues) are a wonderful discovery that helps combat this. (Although food and lifestyle interventions might prevent it in the first place)

“Statins reduce the amount of bad cholesterol int he blood, and so lessen the amount of arterial blockage from the build-up of plaques. Statins also change the heart structure, reducing thickness and volume and reducing the chance of a heart attack.”

Many other interventions related to CVD are mentioned in the book.

Cancer in re(treatment)

“In industrialised nations, about one in two people will develop a form of cancer during their lifetimes, and generally between the ages of 40 and 80. Just under 8 million people die of cancer worldwide each year.”

Immunotherapy is the treatment where the immune system is stimulated to better fight cancer (and this is also how our bodies fight pre-cancerous cells normally). (analogy to a car) “you first have to release the brake, then press on the accelerator and steer where you’d like to go”.

Early therapies only did the first (accelerate), this involved giving patients immune cytokines (which promptly attacked other cells and lead to deadly inflammation). But if the patient did survive, there were long term benefits (cancer not coming back).

CLTA4 is a more targetted (at cancer cells) version of this process.

Analysts predict that 60% of cancers can ben managed by immunotherapies.

Another approach in this direction is CAR-T (chimeric antigen T-cell receptors). Here antibodies are taken outside of the body and manipulated in a lab (and enhanced of course).

Breathing easier in old age – respiratory disease

“[A]ge reduces lung elasticity, respiratory strength and the efficiency of the chest wall in respiration.”

Smoking is a leading cause of respiratory disease. About 10 million people die of this each year.

The categories are:

  1. Diseases of the airways (asthma, COPD, bronchitis)
  2. Diseases of the lung tissues (pneumonia, asbestos)
  3. Pulmonary circulatory diseases (blood vessels get clogged)
  4. Lung cancers

Intervention at the genetic level might be a solution for some of these (e.g. COPD). These are at least a decade away according to the authors.

Diabetes – sweet news ahead

Note: authors might consider Alzheimers as a type of diabetes.

Today 8% of the adult population worldwide has diabetes type 2 (450 million people). Diabetes is associated with many (if not all) ageing diseases (as cause). This is all lifestyle-induced…

Diabetes causes 5 million deaths per year.

Type 1 has a genetic component and affects 1% of people worldwide, it’s medically controlled with insulin. Type 2 starts with insulin resistance, obesity and insufficient exercise are the main causes. Lifestyle changes can reverse it (dieting and exercising). A short period of fasting could reverse type 2 and type 1 diabetes (Valter Longo, The Longevity Diet), in mice!

Metformin was originally developed to combat type 2 diabetes.

The book mentions many other types of drug-interventions (mostly related to insulin) for type 1 and 2.

Don’t forget – the long road for dementia

“[T]he prevalence of dementia and neurodegeneration is actually falling in the developed world.” (1/5th in England and Wales in the span of 22 years).

The different kinds of dementia:

  1. Alzheimer’s 62%
  2. Vascular dementia 17%
  3. Mixed dementia 10%
  4. Dementia with Lewy bodies 4%
  5. Other 3%
  6. Parkinson’s disease 2%
  7. Frontotemporal dementia 2%

“About 32% of people over 85 years old in the US have been diagnosed with Alzheimer’s.” There are 50 million people living with dementia (130 million in 2050 if no new interventions).

Statins don’t protect against dementia. It is characterized (but maybe not causes) by the build-up of protein (Lewy bodies, amyloid plaques, protein tangles) between cells.

There is a strong link between diabetes and dementia. Poor diets might be a cause (processed foods). Gluten is probably ok for 99% of people (not linked).

“It is thought that the accumulation of misfolded proteins is the result of the failure of the so-called chaperone system, whereby proteins are guided into their 3D structures by helper molecules. The failure of autophagy to remove these misfolded proteins, as well as damaged organelles, through lysosomal degradation aggravates the situation in both Alzheimer’s (tau peptides) and in Parkinson’s (a-synuclein protein aggregation).

“About 70% of Alzheimer’s is genetic, so that means about 30% comes from environmental factors.”

There is currently no cure (and many failed) fo Parkinson’s. What we do know is that exercise is good (induces autophagy and clearance of amyloid plaques and tau protein tangles). Genetic interventions will also come with time.

Animal Models

The elegance of works, the fruits of fly research, mouse hunts, and the leavening of yeast

Shorter-lived animals can (with some caveats) be very good proxies for humans (we live too long). Fruit flies, roundworms, mice, and baker’s yeast are some of the most used animals.

One problem with this is that they were selected for short lifespans in the first place. Wild mice, for instance, live much longer than the lab mice. The homogenous(ness) also doesn’t reflect real-life well. Also, telomerase isn’t a (lifespan) issue for mice.

Another avenue of research is to look at long-lived animals and see what mechanisms they have that keep them healthy. The hydra can regenerate indefinitely and FOXO genes seem to be an interesting avenue of research.

Insilico Medicine is a company that uses machine learning (ML) that uses human gene expressions to see if there is a biological age (and where you are on that scale). They also use ML to find new drugs/molecular structures.

Fertility is also a topic of interest and improving IVF (with NAD+ precursors) and getting women ovulating after menopause again is being explored.

Autophagy is the way cells get rid of garbage, “[it] delivers unwanted components from within the cytoplasm to the lysosome, which reduces them to amino acids and other cellular building blocks.” As we age, this process breaks down more often/becomes less efficient. Spermidine might work to keep it going better (reduce inflammation, clean cells).

The Buck Institute is the world’s first independent research institution focused on using ground-breaking research to prevent and cure age-related chronic diseases.

Biomarkers of ageing are quantitative variable indicators of biological age. Inflammation agents, glucose metabolism biomarkers, and others are examples. This type of indicator might better predict health and care needs than chronological age.

Key Opinion Leaders

David Sinclair (Life Biosciences) – Both researcher and entrepreneur (12 longevity companies).

Nir Barzilai – Metformin (2019 trail, also cautionary note: higher Alzheimers?), HDL.

Aubrey de Grey – See Ending Aging, SENS research foundation.

Leonard Hayflick & Laura Deming – Entropy, animal models don’t translate well.

Craig Venter – Sequence Human Genome, Human Longevity Inc.

(etc)

Targets in Ageing

Rules and regulations

If ageing was classified as a disease, things would go smoother. 90% of drugs fail in clinical trials. Phase 2 is to test efficacy (and here most drugs die).

Ageing Vampires

Young blood for old mice! works. The mice experiments probably worked because of the parabiosis (stitching together), the liver and circulatory system (not per se only/primarily the blood itself). But maybe not for humans. Possibly you can administer osteopontin (a protein that is lacking at older age, no transfusion needed). More research is needed.

Caloric restriction

Unpleasant and doesn’t seem to really work for people (i.e. doesn’t translate well from animal models), and is hard/impossible to adhere to. Intermittent fasting might have same/better effect.

AMPK and Metformin

Metformin (antidiabetic drug), and the gene AMPK (adenosine monophosphate activated kinase). Possible life extension effects, TAME trail on the way.

mTOR, Rapamycin and Rapalogs

mTOR stands for mechanistic target of rapamycin, 2 pathways, MTORC1 is the focus. But has side-effects in humans, rapalogs (analogues) are being developed.

Sestrins

A family of proteins, expressed when stressed (activate AMPK).

X

The Longevity Diet

Dr Valter Longo summarises his life long journey of researching longevity through diet. In The Longevity Diet, he argues for a nutritious diet in combination with regular fasting-mimicking diets (FMD). The diet is plant-based (with some fish sprinkled in). The FMD should activate innate programs your body has for restoring youth (juvenescence).

The book offers a compelling argument for the influence of diet on our health. It also makes common sense (which from The AI Delusion I gather we need some more of). Yet it also relies heavily on epidemiological data and studies of centenarians. What I find most compelling is the clinical studies, for which the other two can be a basis/hypothesis.

Two questions remain after reading the book. The first concerns longevity and fitness. In bodybuilding/weightlifting/etc world IGF-1 is touted as a great way to build muscle. Yet it’s also one of the things mentioned in the longevity diet as something to avoid (e.g. red meat) and lower (e.g. FMD). I want to put on some pounds (of muscle) in the coming years, yet also want to live long. So there is a bit of a dilemma.

The second is about the expected effect size of the longevity diet (+FMD). Will it add 5 years? 10 years? And/or how many healthy years (healthspan) will it add? This is something that is quite difficult to study (us being humans and all), and I hope we will be able to make progress in this area in the coming years. At the same time I also think that fixing things at a molecular level (see Ending Aging) should be pursued.

The best thing could be to eat healthy, with some FMD/fasts sprinkled throughout the year, and then also start fixing some things which we can’t keep intact with a good diet, or that need to be partly supplemented with other interventions.

One thing to never lose sight of is the enjoyment of life. Some of the mice in the calorie restriction programs were depressed, for twice the lifetime. I really like the idea of having short (5 days) fasts/FMD 4 times per year. And although I already follow most of the guidelines of the longevity diet (and I want to do that even better), I still love to have a beer or two (or 8) every now and then. So if you want to have a long and healthy life, read on for the rest of my notes on The Longevity Diet.

In the introduction we are introduced to the goal of the book “Contrary to the notion that if we live longer we will extend the ‘sickness’ period, our data indicate that by understanding how the human body is maintained while young, we can stay fully functional into our nineties, hundreds, and beyond. One of your primary ways to achieve this is to exploit our body’s innate ability to regenerate itself at the cellular and organ levels.”

The Five Pillars of Longevity is what Longo builds his research upon:

  1. Basic/juventology research
  2. Epidemiology
  3. Clinical studies
  4. Studies of centenarians
  5. The understanding of complex systems

A lot of the book is dedicated to describing the habits and diets of centenarians. One of the statements in this context is that supplementation doesn’t work (e.g. with antioxidants). The argument is that you can’t improve on an almost perfect system. I understand the concept in relation to what is being tried. Yet at the same time, our system is almost perfect to keep us alive some time after childbirth. In time I do believe we will be able to copy/supplement this system to live even longer.

Another thing he argues for is that we should do things in tune with evolution. Although that phrase itself is quite pointless, the example of fasting is illustrating. Longo argues that in times of low food a species (humans, but also earlier on the evolutionary tree) were right in saving themselves over reproducing (otherwise they wouldn’t be here anymore). So if we trick our body into giving that response, maybe we can set off the same protection and damage repair (on a protein level) process.

What Longo tries to do is to keep a human young, not treating individual diseases or conditions. The process of repair that he argues for, he calls programmed longevity: “a biological strategy to influence longevity and health through cellular protection and regeneration to stay younger longer.”

You are what you eat and food can have a large impact on your health. Yet at the same time Longo argues that your happiness is not determined by the food you eat. Yes a cake (read: sugars) bring you immediate joy, but eating healthy is not something that will make you unhappy. He even argues that it will make you happier, although indirectly, because of better health.

Constant caloric deprivation/deficit is not what you would want. It can expand the life of a mouse, and possibly humans too. But experiments in both show that it’s the opposite of a mood booster. This is one of the main reasons for doing a FMD/fast only at certain intervals.

The Longevity Diet is what you want to be doing for most of the time, it consists of the following parts:

  • Pescetarian diet: Almost 100% plant-based and fish 2 or 3 times a week (for the omega’s – this could be vital, but I wonder how critical/necessary it is)
    • One note is that in old age, Longo argues for more protein in the diet (but it’s based on studies of centenarians and one fallacy of this could be that they didn’t have much protein back in the day and now just have it available (thus eating it more))
  • Consume low but sufficient proteins
    • From plants and nuts
  • Minimize bad (trans) fats and sugars, and maximize good fats and complex carbs
  • Be nourished (Longo argues for taking a vitamin and mineral supplement, I can’t find good evidence that backs it up, and I wonder if it really is beneficial)
  • Eat a variety of foods from your ancestry (again, not 100% convinced, I do get it from a ‘processed’ vs more whole-food approach)
  • Eat twice a day plus a snack (now doing this, and the main benefit is more control/easier measuring of meals)
  • Observe time-restricted eating (eat within 11-12 hours per day or less)
    • The source linked for this is quite a good one, with an intervention (only to eat within the time frame) that lead to weight loss.
  • Practice period prolonged fasting (fasting/FMD for 2 periods of 5 days or more)
  • Follow the above points to reach/maintain a healthy weight and abdominal circumference

I really like the last part, it’s about finding a new diet, not ‘dieting’.

It also triggered me to make some measurements to better assess my progress in body composition (the two scales I have at home are very erratic and give different measures).

Here are some more notes:

  • The age differences between the best and the worst groups are quite small: Okinawa 81,2 vs USA 76,8 (5%)
  • And although some cancer levels are much higher in percentages, up to 8 times as many, the number of prostate cancers in the US is still only 28 per 100.000
  • “If you take 100 centenarians, you get 100 different elixirs of longevity”
  • Longo argues that the drugs we’re developing are still far away and that diet is, now, the best thing you can do yourself (I can concur)
  • Stay active, this is the second factor after diet that has a huge influence on longevity
    • Walk fast for an hour every day
    • Ride, run, swim 30-40 minutes every other day plus two hours on the weekend
    • Use your muscles
  • The FMD could also have positive effects on many diseases. Although things become a bit more speculative here, there is still quite promising evidence and if you (again) compare it to the average diet, I can very much understand how it could help
  • Chapters that follow deal with cancer, diabetes, cardiovascular disease (the biggest killer that gets the least attention), Alzheimer’s, and autoimmune diseases

The book ends with an observation about our minds. A positive mindset, a will to live, and more could be very significant factors in longevity. The trouble is that it’s not very well studied and the implementation of results can be quite hard. But keeping close friends and enjoying life should not be underestimated.

As a final note, I wholeheartedly believe in what Longo says and I am confident that more research will confirm many of the things not yet proven. Yet I also think we should pursue medical/drug interventions with all the haste we can. Eventually things will break down, our genes weren’t ‘made’ to have us live forever. So we will have to come up with ways to do this ourselves. The Longevity Diet is a great basis, a well-oiled car, now we need some mechanics to do some repairs (and upgrades) every now and then.

Note: As mentioned above, centenarian research really isn’t that good. New research shows that record-keeping in these areas is bad and the long ages probably based on lies (or statistical flukes).