As far as useful frameworks for approaching longevity, there is no one better than Peter Attia, M.D. In the field of longevity, he needs no introduction. He has a stellar background* and a knack for communicating complex concepts in a manner that is easy to understand. So when it comes to framing your longevity strategy, Attia is a great place to start.
We recently re-watched this excellent video, where he shares a very straightforward approach to thinking about aging well. Although the video is about four years old, the framework he lays out is just as relevant today. If you have the hour to spare, the video is worth watching, in the meantime here are our key takeaways:
The Short vs. Long Game
While the science of longevity is advancing at an accelerating pace, there are no short-term step-function “improvements” available as of yet. Therefore, your short game should focus on the incremental steps and lifestyle habits you can implement and build upon right now.
Start With The Objective
When it comes to longevity, what are we trying to achieve? The answer seems obvious at first but, like with everything, it gets more nuanced as we dig deeper. As only a doctor with a mechanical engineering degree could, Attia frames the objective of a longevity strategy as a maximizing a function:
Longevity = F (lifespan, healthspan)
If you think of this function as a curve, we want to maximize the area under the curve by pulling on three potential levers:
- Increase lifespan — add years to your timeline.
- Slow the rate of decline — extend healthspan by delaying the onset of chronic diseases.
- Compress the period of morbidity at the end of your life (amount of time you suffer from a chronic disease) to maximize the quality of your later years.
Check out his explanation here.
While some might dispute the importance of living longer, Attia argues that at the very least time buys you optionality. You probably wouldn’t want to trade places with a 90-year old Warren Buffet right now, despite all his billions. Moreover, the more years you can add to your lifespan, the likelier it is that you will be able to take advantage of the step-function improvements coming from longevity science companies. The flipside, is that you wouldn't want to add years to life if you are suffering from a chronic disease that greatly diminishes the quality of your days. Therefore the focus on healthspan.
Of the three levers that can impact the area under the curve, healthspan is were you can exert the biggest impact. Attia helpfully breaks this down into 4 key building blocks and highlights the elements that are crucial in each:
- Mind: your cognitive health — (1) short-term memory, (2) processing speed, and (3) executive function.
- Body: (1) maintenance of muscle mass; (2) ability to perform functional movements (e.g. hip hinges); (3) freedom from pain / chronic injuries.
- Stress tolerance: ability and tools you have at your disposal to deal with the stress in your environment.
- Sense of purpose and social support. Level of engagement and social interaction.
The focus of the lecture is on the first two elements, as they are the most critical for longevity. But, he argues, it is hard to think you would consider yourself as having a high quality of life if any of these four essential building blocks is missing.
Develop A Strategy
One of the biggest challenges in defining the right approach to longevity is that its study is not amenable to conducting experiments on humans the way you do when developing drugs or treatments (they take very long, can pose ethical questions, etc.).
So, it is important to frame your longevity strategy on as solid a foundation as possible. The next best thing to clinical experiments is zeroing in on the most applicable indirect evidence on how the aging process can be modified. In Attia’s case, he focuses on three things:
- What we can infer from analyzing centenarians.
- What has proven to be effective in animal studies.
- Molecular insights gained at the cellular level.
The study of centenarians has long been the focus of many longevity experts. The key question is what can we discover from their genotypes and phenotypes that could be useful?
It turns out that there are about a dozen or so genes identified so far that tend to cluster in exceptionally longed-live people. Although there is not much that can be done about the genes we inherited, once we understand the role that these genes play in centenarian longevity, we can get creative about trying to mimic the phenotype. By making changes to our lifestyle we can impact the way genes get expressed.
Most of the genes associated with longevity have some clear connection with the biomechanics of multiple chronic diseases. In the end, centenarians die of pretty much the same causes as the rest of the population. In their cases though, the onset of chronic disease happens much later in life. This suggests that our focus should be invested in better understanding the causes of the main killers: cardiovascular and cerebrovascular disease, cancer, and neurodegenerative disease (eg. Alzheimer’s), account for more than 60% of deaths in people over 65).
Although all these maladies are well known, our understanding of them is getting more nuanced. A great example is the evolving view of heart disease. For a long time, conventional wisdom was that cardiovascular disease (CVD) is a function of high cholesterol. Now, it is understood that CVD is not a cholesterol disorder but rather a lipoprotein inflammatory disorder. That is at the heart of the recent controversy on beef and saturated fats. If more doctors were to embrace this view, Attia posits, many more cases could be prevented.
Since longevity experiments are difficult to perform in humans, the best next thing is to try to make inferences from what is observed in non-human studies. The criteria that Attia proposes using is focusing on the interventions that have been shown to successfully extend longevity across the biggest range of organisms: from yeast to flies to worms to mammals. His rationale is that if something has proven to work consistently across over a billion years of evolution, then making a leap of faith that if also applies to humans is easier.
Applying this high bar, he points to three strong conclusions:
- Some combination of caloric restriction and dietary restriction matters. It has been shown to extend longevity across many species.
- Of all the drugs that have been tested across organisms, the one that has worked uniformly in extending lifespan and healthspan is Rapamycin. This drug is believed to regulate a protein called mTOR, which has a role in determining how the organism senses nutrients and responds to stress.
- Genetic insights. Genetic interventions on animals can help us to think causally about the genes and phenotypes we see in human centenarians. For example, it has been observed that attenuation of the DAF2 gene in worms extends their lifespan & healthspan by 2.5x. As a result, much interest is being focused on the IGF1 gene, which is thought to be the equivalent of the DAF2 genes in humans.
Based on the study of centenarians and animal models, there is much to be learned about longevity by focusing at the level of the cell. In particular, there are four processes where most of the attention of cutting-edge longevity science is focused on:
- Nutrient sensing – how our cells respond to the type of nutrient density we find today.
- Autophagy – the mechanism by which cells remove unnecessary or dysfunctional components inside them.
- Senescence – the process by which some cells cease to grow and divide but don’t die, they become “zombie” cells.
- Inflammation – the cell’s response to external stressors.
These processes are all relate the hallmarks of aging, and are the research target of many longevity-science startups. Understanding these processes and how to reverse them will lead to many breakthroughs in extending longevity in the next 5-10 years.
See a great recap here….
The three pillars of a framework for a longevity strategy
Tactics: Where The Rubber Meets The Road
With a clear understanding of the objective and the strategy, we have a good foundation to define our longevity protocol: the tactics, habits and practices we can adopt to maximize that space under our longevity curve.
Attia organizes tactics into 8 buckets:
- What you eat (e.g., managing your glucose levels, intermittent fasting)
- How you exercise (e.g., type-2b muscle fiber activation; zone II training)
- How you sleep (e.g., hormone signaling, recovery)
- How you manage stress (e.g., breath work, meditation)
- What drugs you take (e.g., Rapamycin, Metformin)
- What supplements you take (e.g., Omega-3s, magnesium)
- What hormones you take (e.g., testosterone)
- And your ability to learn and unlearn behaviors
There is a ton that can be discussed in each one of these, and many innovations are happening as we speak. The important thing is that with this basic structure, you now have an excellent framework for you to think about the best way to approach your longevity protocol.
* Attia has degrees in mechanical engineering, applied mathematics, and medicine from Stanford; was a surgeon at Johns Hopkins Hospital for 5 years; and a surgical oncology fellow at the National Cancer Institute for two years. He now runs a private practice focused on longevity, based in San Diego and New York. He creates lots of content on longevity and is very visible on social media.