Section 1.1: Insights from Dr. David Sinclair

According to Dr. Sinclair, significant advancements have been made in extending lifespan and even reversing aging in mice through calorie restriction and specific molecules. Fasting has demonstrated the ability to prolong the lifespan of mice due to the activation of sirtuin genes, which are found in all living beings, including humans. These genes play a protective role against aging and disease.

“When we experience hunger, sirtuins mobilize our body's defenses,” Sinclair explains. “Having regular periods of hunger is essential for activating these protective mechanisms.”

Sirtuins rely on a molecule known as NAD, which declines as we age. By the age of 50, humans typically have about half the NAD levels they had at 20. Research shows that increasing NAD levels in mice can extend their lifespan, shield them from diseases, and even reverse some aging effects. This is often achieved using a molecule called NMN, a precursor to NAD. While human trials are still underway, Sinclair has personally taken NMN for years.

A more affordable alternative to NMN is Nicotinamide Riboside. Sinclair also incorporates Resveratrol into his regimen, a compound that has been shown to enhance the health benefits of NMN. He likens Resveratrol to an accelerator for sirtuins, while NMN acts as the fuel.

Combining fasting, nutritious foods, exercise, NMN, and Resveratrol yields the best results. For instance, when mice received both NMN and exercised, their lifespan surpassed that of those receiving either one alone.

Sinclair consumes 1 gram of NMN and 1 gram of Resveratrol daily, mixing the latter with yogurt to enhance absorption. Resveratrol is naturally present in grape and blueberry skins, but in limited amounts. The concentration is higher in red wine, though still not substantial.

He considers these supplements safe for himself, reporting increased energy levels since starting NMN. His 80-year-old father, who also takes NMN and Resveratrol, remains active. Sinclair, at 50, appears to be in his 40s, despite not having a family history conducive to longevity.

In addition to supplements, Sinclair adheres to a healthy lifestyle, which includes regular exercise, meal skipping, avoiding sugars and carbs, consuming plenty of leafy greens, and undergoing temperature stress through hot and cold exposures. He takes Metformin, a diabetes medication, suggesting it may also prevent cancer and heart disease in non-diabetics, despite a potential decrease in athletic performance.

Temperature stress, achieved by alternating between saunas and cold baths, is believed to activate longevity pathways in the body, akin to the effects observed in laboratory yeast.

Sinclair previously followed the Okinawan diet, known for its association with exceptional longevity. Okinawans often exhibit a blend of good genetics and healthy practices: they remain active throughout life, fast, consume ample vegetables and fish, and practice moderation in portion sizes.

Damage to the "epigenome," which affects how our genes are read, is a significant factor in aging. Sinclair is cautious about excessive radiation exposure, which can accelerate this damage, and therefore limits x-rays and sun exposure. He also monitors his iron intake, particularly as high iron levels can harm cells.

Notably, researcher Aubrey de Grey posits that while these practices may extend lifespan, the impact may be minimal—around 3 to 5 years. Larger organisms like humans likely experience less benefit from these methods compared to smaller animals like mice. However, fasting has been linked to a reduction in illness among humans.

Section 1.2: Insights from Dr. Valter Longo

Dr. Longo emphasizes the importance of moderation in fasting. He advises against fasting for more than 12 hours at a time to minimize risks such as gallstones and muscle loss. For extended fasting, he recommends a "fasting mimicking diet," which involves calorie restriction (800 to 1100 calories) for 4 to 5 days, starting with 1100 calories on the first day and decreasing to 800 on subsequent days. This approach has shown significant health benefits.

For those in relatively good health, undergoing this diet 2 to 4 times a year is generally sufficient. The diet focuses on vegetables, nuts, olive oil, vegetable soups, and a fish oil supplement, while avoiding animal proteins, sugar, and carbs (excluding vegetables).

Fasting and calorie restriction encourage the body to eliminate damaged cells and shed excess body fat, particularly harmful visceral fat that surrounds internal organs.

A typical daily diet should be confined to a 12-hour eating window, with 3 meals and a small snack consumed during that time. Overweight individuals may benefit from reducing to two meals. Interestingly, skipping breakfast has been correlated with an increased risk of heart disease.

Caloric needs vary based on factors like body weight and age. For instance, a 190-pound man may require about 2500 calories daily, whereas women typically need between 1800 and 2000 calories.

Longo recommends a balanced intake of nutrients: 60% complex carbohydrates (primarily vegetables), 30% healthy fats (mostly from fish and olive oil), and 10% protein (from fish, nuts, and legumes). Diets high in saturated and trans fats are linked to a higher risk of disease and premature death.