<p><a href="https://peterattiamd.com/mattkaeberlein3/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=220912-pod-mattkaeberlein3&utm_content=220912-pod-mattkaeberlein3-podfeed"> View the Show Notes Page for This Episode</a></p> <p><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=220912-pod-mattkaeberlein3&utm_content=220912-pod-mattkaeberlein3-podfeed"> Become a Member to Receive Exclusive Content</a></p> <p><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=220912-pod-mattkaeberlein3&utm_content=220912-pod-mattkaeberlein3-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>Dr. Matt Kaeberlein is a globally recognized expert on the biology of aging and recurring on The Drive. In this episode, Matt explains his research findings on nutrition as it relates to aging and longevity, including the results from his recent review article in Science. From there, he and Peter dive deep into the literature on calorie restriction (CR), explaining the nuance, benefits for lifespan and healthspan, and potential downsides of CR. He discusses the epigenetic changes that occur with age and potential benefits and downsides of epigenetic reprogramming, often viewed as a panacea for reversing aging. Matt also explains the impact of dietary protein on aging, including the interesting dichotomy around how protein, a critical macronutrient, and rapamycin, a geroprotective molecule, have opposite effects on mTOR. Additionally, he talks about low-protein vs. high-protein diets and their effects on muscle mass and mortality, as well as the impact of IGF-1 signaling and growth hormone on lifespan.</p> <p>We discuss:</p> <ul> <li>Challenges with understanding the effects of nutrition and studying interventions for aging [3:30];</li> <li>How Peter's and Matt's convictions on nutrition and thoughts optimal health have evolved [8:15];</li> <li>Calorie restriction for improving lifespan in animal models [16:15];</li> <li>Utility of epigenetic clocks and possibility of epigenetic reprogramming [22:00];</li> <li>Mutations and changes to the epigenome with aging [31:45];</li> <li>Epigenetic reprogramming: potential benefits and downsides and whether it can work in every organ/tissue [35:15];</li> <li>First potential applications of anti-aging therapies and tips for aging well [43:00];</li> <li>Impact of calorie restriction on the immune system, muscle mass, and strength [47:00];</li> <li>Insights from famous calorie restriction studies in rhesus macaques [55:00];</li> <li>An evolutionary perspective of the human diet [1:03:45];</li> <li>Antiaging diets: Separating fact from fiction—Matt's 2021 review in Science [1:12:30];</li> <li>Mouse models of time-restricted feeding in the context of calorie restriction [1:19:30];</li> <li>Nutritional interventions that consistently impact lifespan in mice, and concerns around efficacy in humans [1:27:00];</li> <li>Differing impact of calorie restriction when started later in life [1:31:00];</li> <li>Lifespan extension with rapamycin in older mice [1:37:15];</li> <li>Relationship between protein intake and aging, and mouse studies showing protein restriction can extend lifespan [1:43:30];</li> <li>Impact of protein intake on mTOR, and why inhibition of mTOR doesn't cause muscle loss [1:50:45];</li> <li>Low-protein vs. high-protein diets and their effects on muscle mass, mortality, and more [1:55:30];</li> <li>The impact of IGF-1 signaling and growth hormone on lifespan [2:06:30];</li> <li>Parting thoughts on the contribution of nutrition to healthspan and lifespan [2:19:45];</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p>
Actionable Insights
1. Prioritize Exercise Over Nutrition
Focus your mental energy and time on exercise for a much higher return on investment (ROI) compared to incrementally optimizing nutrition. Getting most of the nutritional benefits is sufficient, while exercise offers greater gains for additional effort.
2. Achieve Basic Fitness Baseline
Before debating the fine points of nutrition, ensure you have a foundational level of physical fitness, such as being able to deadlift twice your body weight and perform 15 pull-ups. This emphasizes the importance of fundamental strength and activity.
3. Aim for “Good Enough” Nutrition
You don’t need to optimize every single nutritional detail; getting close to optimal total caloric intake and maintaining a healthy body composition provides most of the benefits for health. Prioritize broad healthy eating over minute optimization.
4. Choose Whole, Recognizable Foods
Prioritize foods that your great-grandmother would recognize, typically found on the perimeter of a grocery store, as they carry inherently less risk than processed items with many ingredients. This emphasizes a focus on natural, unprocessed food choices.
5. Hedge Against Future Cures
Do not rely solely on future scientific breakthroughs to reverse aging; instead, adopt a risk management approach by actively caring for your health now. Treat your life as your most important asset and hedge against uncertainty.
6. Manage Expectations for Cures
Do not expect major changes in treatments to improve lifespan and healthspan within the next 20 years, as the scientific and regulatory path is long and complex. This encourages focusing on current, proven health strategies.
7. Increase Protein Over 50
If you are over 50 and exercising, aim for a dietary protein intake higher than the Recommended Daily Allowance (RDA) for beneficial health outcomes. This helps maintain muscle mass and function as you age.
8. Optimize Protein for Muscle
To optimize muscle protein synthesis, aim to consume approximately one gram of protein per pound of body weight, spread into four servings of about 0.25 grams per pound each. This helps ensure amino acids are utilized efficiently for muscle growth rather than oxidized.
9. Pair Protein with Resistance Training
To maximize muscle mass and strength, combine adequate protein intake with hypertrophy (resistance) training. Protein alone makes some difference, but the synergy with training is far greater.
10. RDA Is Minimum Protein
Understand that the Recommended Daily Allowance (RDA) for protein represents a minimum to prevent muscle wasting in sedentary individuals, not an optimal amount for active people or those seeking to build muscle.
Evaluate your health by asking: are you overnourished or undernourished, under-muscled or adequately muscled, and metabolically healthy or not? This framework helps determine individual nutritional and exercise needs.
12. Aim for 15 MET-Hours Exercise
To capture a significant portion (30-50%) of the full health benefits of exercise, aim for at least 15 MET-hours per week, which could be achieved through activities like three hours of brisk walking or slow jogging.
13. Be Open to Changing Beliefs
It is crucial to be willing to change your beliefs about nutrition and other health aspects as new scientific data emerges. This promotes adaptability and evidence-based decision-making.
14. Recognize Study Limitations
Be careful about assuming causation from correlation, especially in backward-looking epidemiological studies or when extrapolating animal study results to humans, due to changing environments and biological complexities.
15. Verify Rapamycin Bioavailability
If taking rapamycin, be aware that compounded versions in capsules may have significantly lower bioavailability than brand-name serolimus (Rapamune) pills due to gastric pH instability. Consult your physician and pharmacist.
16. Caution with Extreme CR
Be realistic about the psychological consequences (e.g., constant hunger, social isolation) and potential immune deficits associated with extreme caloric restriction in humans. Ensure optimal micronutrient intake if pursuing CR.
17. Avoid High Protein with Sedentary
If you are overweight, obese, or diabetic and sedentary, a high-calorie diet combined with high protein intake could be problematic. Ensure your protein intake is balanced with your activity level and metabolic health.
Be cautious about over-interpreting total IGF-1 levels as a definitive biomarker for aging or health, especially in individuals over 50, as its signaling activity is complex and influenced by many factors.