Fasting and Biological Age With Dr. Valter Longo

Yes, it is possible to have a 20-year difference between your chronological age and biological age. Research conducted on U.K. twins showed that individuals could have a biological age that is significantly different from their actual age. For example, a 40-year-old could have a biological age of 65, while a 65-year-old could have a biological age of 40. This disparity in biological ages can impact life expectancy, with those having a younger biological age likely to live longer. Various tests can be conducted to determine biological age, such as epigenetic tests, telomere tests, and metabolomic tests. While these tests may not always agree with each other, they can provide valuable insights into individual aging processes. Most doctors can order these tests for patients, with options including epigenetic tests, blood marker-based tests, telomere tests, and metabolomic tests. While telomere and metabolomic tests may be less readily available, epigenetic and blood marker-based tests are more common and can offer useful information about biological age. Dr. Valter Longo transitioned from studying aging in people and mice to yeast in the biochemistry department at UCLA in search of concrete answers. In the early 90s, he focused on the genetics of aging and identified the TOR S6 kinase pathway in yeast, which is activated by certain amino acids and accelerates aging. His groundbreaking work led to the discovery that rapamycin, a drug that blocks this pathway, can extend lifespan in mice. Essentially, nutrient sensing in cells plays a crucial role in determining cell growth, repair, and aging. Longo's research shows that too many specific nutrients, like amino acids and carbohydrates, can actually speed up the aging process. This phenomenon can be likened to a power-saving mode in a phone, where conserving energy allows for longer-lasting function until more nutrients become available. This evolutionary adaptation enables organisms like yeast to enter a maintenance mode and wait for optimal conditions to reproduce and thrive. However, recent scientific research suggests that maybe hibernation isn't necessary for slowing down the aging process. Instead, the focus is on being in a very active but non-reproductive state. Most individuals don't reproduce frequently throughout their lives, so why are we always in a pro-reproductive mode? What if we shifted to maintenance mode, remaining highly functional and active, while utilizing protection mechanisms until reproduction is necessary? This knowledge can be used to age more slowly without the need for hibernation.

When it comes to aging, everyone goes through the same processes, but individuals can age at different rates. Genetic factors play a significant role in how quickly someone ages. For example, individuals with a growth hormone receptor mutation in Ecuador live longer and have a lower risk of diseases. Certain genetic variations can predispose individuals to live longer, along with lifestyle choices and environmental factors. While genetics play a role in determining lifespan, lifestyle choices and environmental factors have a greater impact on aging in the general population.

Fasting is another factor that can influence gene expression and aging. Fasting can cause significant changes in the body, potentially more than any other intervention. For example, fasting for five days can lead to significant changes in the body's gene expression. This highlights the potential of fasting as a tool for slowing down the aging process and promoting longevity. To achieve a state where the body burns fat and relies on fatty acids and ketone bodies for energy, one must tap into the internal energy source. Ketogenesis is the process of producing ketone bodies from fat breakdown, which the body then reprocesses. After a few days of fasting, the brain can function on both glucose and ketone bodies, while the heart can use fatty acids. Glycerol and amino acids can be used for gluconeogenesis to produce glucose when no external carbohydrates are consumed.

Autophagy, the process where cells self-cannibalize to eliminate accumulated junk, typically takes about five days of fasting to become noticeable in the blood. While fasting for shorter periods may not induce autophagy, there are still positive impacts on the body. Time-restricted eating, such as a 12-hour fasting period, can improve health without the potential negative effects associated with longer fasting durations. Studies in mice suggest that such eating patterns can reduce biological age and potentially prolong lifespan. However, prolonged fasting periods of 14-18 hours or more may have short-term benefits but could potentially lead to increased mortality in the long run. Many drugs and interventions, such as GLP-1, may provide short-term benefits but may not consider the long-term effects. Fasting, on the other hand, has shown to be powerful and safe, especially with a 12-hour fasting period. Studies have shown positive effects on aging and metabolic issues with this approach. The ZOE Big If study, which focused on time-restricted eating, had over 140,000 participants, with a third finding it easy to adhere to and experiencing benefits such as weight loss and improved mood. Personalization is key, as some may find it harder to fast for long periods. The importance lies in sustaining the practice for long-term benefits. Dr. Valter Longo's fasting-mimicking diet is another approach that treats fasting like medicine, showing promising results for longevity and disease resistance. We applied our knowledge to identify four markers - IGF 1, IGF PP1, glucose, and ketone bodies - to assess the effects of fasting-mimicking diets and water-only fasting. By combining these findings with periodic fasting, we developed a low-calorie, low-protein, low-sugar, high-fat plant-based diet lasting four to seven days. This regimen, known as the fasting-mimicking diet, has shown promising results in treating various conditions, including diabetes.

Through clinical trials, we have observed significant improvements in patients, with some experiencing diabetes regression and reduced drug use. The concept of periodic fasting-mimicking diets, done once every few months, has shown to not only improve health but also potentially reverse biological aging. Long-term studies are ongoing to assess the sustainability of these effects and to determine the optimal frequency of fasting cycles for maximum benefits. Damage to the kidney initiates the cycles of the fasting-mimicking diet, causing the kidney to activate developmental genes, such as Yamanaka factors, which can reprogram cells into a young pluripotent state. Special transcriptomics show the disruption caused by toxins, but the fasting-mimicking diet restores gene expression to normal, allowing the body to reset and repair itself.

In a pilot trial with 13 patients, the fasting-mimicking diet showed long-term benefits in kidney disease markers after just three cycles. Larger trials in various diseases are promising, with universities conducting studies on diabetes, Crohn's disease, colitis, and more, based on the success seen in animal models.

The fasting-mimicking diet involves a specific protocol of low-calorie, low-sugar, low-protein, high-fat meals tailored to different conditions. While fasting can promote longevity, a holistic approach to anti-aging includes a healthy daily diet, avoiding ultra-processed foods, maintaining muscle mass, and caring for gut health to reduce inflammation and support the aging process. Tim will explain the information to me later, as I think I only grasped half of it. In summary, biological age is not the same as chronological age. Your lifestyle can determine whether your body is that of a younger or older person, regardless of the number of birthdays you've had. Valter's research on mice showed that changing one gene and calorie restricting them could double their lifespan. Fasting has a significant impact on our biology, as it triggers a profound shift in our bodies to ensure survival.

Time-restricted eating, limiting eating to 12 hours and fasting for 12 hours, is believed to help maintain youthfulness. Tim suggested that fasting for 14 hours a day may be safe. Both Tim and Valter agreed that very short eating windows of six to eight hours may not be healthy. Valter introduced the concept of a fasting-mimicking diet, which involves eating a specially designed low-calorie meal for five days, three times a year, to trigger a fasting-like response without complete starvation.

Valter's studies showed that participants who followed the fasting-mimicking diet saw improvements in their biological age. However, both Valter and Tim emphasized the importance of not overdoing it and waiting for more long-term data on the diet's effects. Tim highlighted the significance of maintaining a healthy diet beyond fasting, especially avoiding high levels of ultra-processed foods.

Overall, the discussion emphasized the potential benefits of fasting and the importance of considering diet in conjunction with fasting for optimal health. sentence: The quick brown fox jumps over the lazy dog.

Rewritten sentence: A speedy brown fox leaps over a lethargic dog.