My Top Five Take Aways from Age Later by Nir Barzilai
I was blown away by something other than Nir Barzilai’s scientific credentials while reading Age Later for this review.
His research credentials are unrivalled. But after reading Age Later, Nir’s skills as a storyteller is what stayed with me. Among the pages of ground-breaking research are warm, touching stories of real people. Many are centenarians, and many of them lived active, fulfilling lives – right to the end.
Age Later digs into cellular mechanisms, genes, and diets of super-centenarians. It provides a compelling a template for what a long, healthy, and active life could look like.
I had a long list of take aways from Age Later.
One of them stood out. This concerns the popular angle of people that live in ‘Blue Zones.’
Age Later: What If Blue Zones Were a Red Herring?
Nothing gets my attention like a new angle on an old ‘truth.’
For as long as I can remember, the ‘blue zones’ have been revered. And Nir Barzilai knows more about them than anybody.
People in some Mediterranean islands, Japan, California, and spots in Central America live statistically longer and healthier lives than the rest of us. Their diet has been a focus. And their community bonds, genes and drinking habits are extensively studied.
In fact, a lot of diet advice is extrapolated directly from the ‘Med Diet’ to our plates and supplements.
The new angle in Age Later got me sitting up and paying attention.
Nir Barzilai said that people who lived in similar places, with similar diets and habits did not always live super-long lives.
This is interesting from two perspectives:
- First, we should question the cause-and-effect relationship of food, lifestyle, and aging.
- Second, with multiple control groups (people with similar diets and locations), there is an opportunity to look deeper into the overlap between genes, diet, and aging.
That is exactly what Barzilai and his team at Albert Einstein College of Medicine in New York has done – albeit with long lived individuals closer to their New York home.
Age Later Book Review Take Aways: Cholesterol / Gene Interactions
LDL Cholesterol is a significant risk factor for heart disease, strokes, and diabetes. Good (HDL) Cholesterol is the opposite, triggering breakdown of harmful molecules in the liver.
What Barzilai showcased is that the Cholesterol / Longevity link is not straightforward.
His work with Centenarians and their offspring uncovered gene pathways which qualify an individual outcome to cholesterol. Two have been studied extensively. They are CEPT and APOC3.
- CEPT: Cholesteryl ester transfer protein. 18% of centenarians had a mutation which inhibited the action of this gene.
- APOC3: 20% of them had a mutation in APOC3 which resulted in higher levels of ‘good’ cholesterol.
Nir Barzilai next looked at whether these genes were specific to Cholesterol – or have wider applications for longevity. The results are encouraging. Lower cognitive decline markers and later average onset of cancers are noted – as well significantly lower cardiovascular disease. More work is needed on these results.
Unfortunately, development of CEPT inhibitors by Pfizer was halted due to high-blood pressure side effects in safety trials.
Age Later Book Review Take-Aways: Growth Hormone and Longevity
I enjoyed the opening passages of multiple chapters of Age Later. The contradiction introduced at the start of the chapter on Growth Hormone piqued my interest immediately.
We know that bigger animal species have longer lifespans. Whales can live to 200+ years.
This would point to growth being a positive for longevity.
The contradiction is that within each species. Smaller individuals live longer. Think small dogs (or dwarf mice).
IGF-1 is widely studied. This growth hormone triggers growth, reproduction, and regeneration of cells. It helps with cognition (in rat studies) and boosts metabolism. Unfortunately, too much of it is clearly associated with cancers.
IGF-1 Receptor Mutations
Research at Einstein located a receptor of IGF-1 which was different in the DNA of centenarians. This shows that one or more gene mutations lower the uptake of IGF-1 into the cells.
Work is ongoing in this area. Genes including FOXO3a are being studied to see if there are pathways to manage IGF-1 uptake during different periods of life.
Age Later Book Review: The World of Mitochondria
Nir Barzilai certainly opened my eyes when it comes to Mitochondria. Their history going back a cool billion years was just to get started.
Like many people, I was aware of the role of mitochondria as power-plants for cells. I wrote about the ATP / ADP energy cycle here at the Age Well Times.
Age Later explains the ‘hidden’ role of mitochondria in creating peptides – hundreds of them. Where you have a peptide, you have potential pathways and interactions via cellular pathways. The obvious questions are what are these peptides doing, and can any pathways be harnessed for longevity?
One peptide – Humanin – has already borne fruit. This has been linked to insulin pathways via the hypothalamus. The kicker is that Humanin production declines with age.
Legal / patient issues have slowed research into Humanin and Mitochondrial peptides. Let’s hope a solution is found soon.
Nir Barzilai: The TAME Study and Metformin
Aging is currently not treated as a disease. The knock-on effects are huge.
Since doctors can’t prescribe something to fix aging, the drug companies can’t be paid. They get paid handsomely for drugs which fix the outcome of aging (all the killer chronic conditions), so why change?
The TAME study is an important first step. The US Food and Drug Administration have OK’s the first major clinical trial for aging. I covered this in depth here (Add Link to TAME Article when published)
This is a six-year controlled study that will test the effect of Metformin on the hallmarks of aging. It is different to previous studies that test effects against individual age-related diseases with overall mortality as a side note.
TAME is approved by the FDA and is overseen by the American Federation of Aging Research. Barzilai formed AFAR and is a key player in the TAME study.
Metformin Controversy and TAME
There is some controversy surrounding TAME. It is not addressed in the Age Later book, though worth noting as an aside to the review. The opposing opinion is that testing Metformin is a waste of money. Any effect on longevity will be mild, and there are far better candidate drugs.
This is a fair point. After reading Age Later and watching Nir speak at conferences and on Podcasts, I firmly believe that once aging is flagged as a treatable disease by the FDA and other governmental bodies, the floodgates to funding will open.
However you rank the candidate drugs, everyone should hope that the TAME study is a success.
Age Later Book Review: Making Eighty the New Sixty
This section starts with sobering demographic statistics. With 435 million people aged 80 or over by 2050 (only 28 years away at the time of writing), our healthcare services will be under stress.
Aging is the common cause of diseases which will affect half a billion people when you include people affected younger. Add obesity levels rising and smoking rates stubbornly high globally and you will see the magnitude of the problem.
Barzilai set out a series of ideas for tackling this slow-motion disaster.
I enjoyed both his practical approach and optimistic tone. Cooperation between labs, business and government agencies is a solid starting point. Funding for clinical trials is also key.
There is a section on separating our messaging from practical near-term health span / lifespan extension and the ‘immortality’ camp. My view is that the LEV (longevity escape velocity) is a future goal – and unlikely to affect me personally. I see it as the second phase. LEV alienates many of the regulators and businesspeople we need on board in a way that 20+ years of health span extension does not. When that is the ‘new normal,’ LEV can have its day.
Age Later is Required Reading for Anyone Interested in Healthy Aging
Age Later ends with some practical tips on making the most of your years and the treatments available.
Drugs (current and future), hormetic stress, antioxidants, muscle mass attrition, exercise and diet are all covered.
Again, it is the conversational style, relatable anecdotes about real people and a constant reminder that understanding the interactions of longevity pathways is work in progress that made this stand out.
Final Thoughts on Age Later by Nir Barzilai
Nir’s storytelling and accessible writing deliver complex science beautifully.
I enjoyed this book every bit as much as ‘Lifespan.’ I’m also glad that I read it after already being steeped in the world of longevity.
Age Later is information dense. That makes it useful to understand the different concepts first. If not, you’d be jumping onto your phone every five pages to look at the details of some biological pathway or another.
Nir Barzilai’s involvement in the world of aging is legendary. The work on Centurions, AFAR, TAME Study, plus collaborations with business and the crème of research scientists cannot be overstated.
To do all this and be such an engaging writer… well, for me that is a one-of-a-kind skill set.
You can find Age Later at your favourite online bookstore. As usual, no link to Amazon from me – I don’t want any reviews here to be biased with commercial intent.
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