41. Andrew Huberman, is that you?

Hi friends,

Welcome to the 41st dispatch of How Humans Flourish, a research-informed newsletter on how we thrive as humans.

This month, we’re continuing our exploration of Lifespan: Why We Age—and Why We Don’t Have To by Dr. David Sinclair, the Harvard geneticist revolutionizing how we think about aging. His Information Theory of Aging is clear: aging is not inevitable—it’s a condition we can treat, slow down, and eventually reverse.

Today, we’ll dive into three fascinating pillars that Dr. Sinclair highlights for their role in longevity. While these strategies won’t reverse aging, they have been shown to extend healthy life.

Calorie Intake: Less Can Be More

Dr. Sinclair emphasizes that reducing calorie intake isn’t just about weight loss—it’s about triggering survival mechanisms in the body that repair and maintain our cells. Controlled calorie restriction, particularly intermittent fasting, activates what he calls “longevity genes” like AMPK and sirtuins, which are our body’s built-in repair teams. This process, known as autophagy, cleans up old and damaged cells, ensuring our bodies function optimally for longer.

In many ways, this mirrors habits found in places like the Blue Zones, where people naturally eat less or follow the rule of “Hara Hachi Bu”—eating until they’re 80% full. Sinclair takes this idea further, showing that controlled hunger itself is a trigger for our body to shift into repair mode, a process critical for slowing aging.

Amino Acids: Striking a Balance

While we need all nine essential amino acids for our bodies to function properly, Sinclair points out that where we get these amino acids makes a big difference. While meat provides all nine amino acids, diets heavy in animal protein, particularly red and processed meats, are linked to higher risks of cancer and heart disease. What’s more, consuming too many amino acids from these sources can actually inhibit the repair processes that are crucial for longevity.

A diet that’s lower in animal protein puts the body under mild stress—enough to activate those same survival circuits that focus on repair instead of growth. This aligns with the wisdom seen in traditional diets rich in beans, lentils, and vegetables, which not only provide the necessary amino acids but also support long-term health.

Temperature Regulation: The Cold Effect

Exposing our bodies to colder environments—whether it’s a brisk walk in cool weather or lowering the thermostat at night—can activate brown fat, a type of fat that burns energy and helps regulate our metabolism. Studies have shown that mild cold exposure can activate genes related to longevity, potentially increasing lifespan.

Research is still determining the optimum process and timing for cold-water immersion sessions, but his most striking example comes from a 2006 study where genetically modified mice, kept just half a degree cooler than normal, lived 20% longer (for female mice) and 12% longer (for males). That’s the equivalent of adding about seven healthy human years for women and about five years for men.

While cryotherapy and cold plunges are gaining popularity, Sinclair reminds us that even simple adjustments—like spending time in cooler environments—can activate these protective mechanisms.

Heat Exposure: The Sauna Effect

On the opposite end of the spectrum, heat exposure, especially through sauna use, can have its own positive effects on our health. Studies have shown that regular sauna use multiple times a week, especially for men, is linked to a significant reduction in cardiovascular disease and all-cause mortality.

The Future of Longevity

Places like the Blue Zones offer a great starting point for understanding longevity. Their habits—natural caloric restriction, plant-based diets, and exposure to mild environmental stress—are key. But as science advances, we’re beginning to see how we can push even further, directly targeting the cellular mechanisms that drive aging.

With gratitude,

P.s. It’s beyond the scope of this newsletter, but in chapters 5 and 6 he shares the potential of products like rapamycin, Nicotinamide mononucleotide (NMN), and metformin in extending lifespan. He also shares some very early research on metabolic compounds that he claims reversed menopause in mice. If this is interesting to you, I highly recommend reading.

P.p.s. If you want to really fall down the rabbit hole, here is a two hour interview with Dr. Sinclair and neuroscientist Andrew Huberman.