cover of episode #324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.

#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.

2024/11/4
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Peter Attia: 本期节目邀请了世界知名的肥胖、新陈代谢和衰老专家Eric Ravussin博士，讨论饮食、热量限制和宏量营养素对寿命和代谢健康的影响。节目涵盖了能量消耗的测量方法、能量平衡、食物摄入和食欲调节，以及关于宏量营养素操控的关键研究。此外，还深入探讨了CALERIE研究（关于热量限制的研究），重点关注与原发性和继发性衰老相关的生物标志物，并探讨了GLP-1激动剂模拟这些效果的潜力以及人工智能和技术如何改变未来的代谢研究。 Eric Ravussin: 我在宾夕法尼亚州立大学彭宁顿生物医学研究中心领导营养肥胖研究中心，并担任糖尿病和代谢学道格拉斯·L·戈登讲席教授。我的研究涵盖了肥胖、新陈代谢和衰老等领域，发表了600多篇同行评审论文。我的工作重点是测量能量消耗，这在技术上极具挑战性。我们讨论了各种测量方法，包括当今被认为是黄金标准的间接量热法。我们还探讨了能量平衡、能量消耗和食物摄入以及食欲调节。我们还讨论了我进行的一项重要研究的结果，该研究考察了操纵宏量营养素比例对能量消耗的影响。我们深入探讨了CALERIE研究，该研究考察了热量限制及其对原发性和继发性衰老生物标志物的影响。我们还讨论了GLP-1激动剂模拟热量限制益处的可能性，并展望了这项研究的未来以及人工智能等新技术进步可能发挥的作用。 Peter Attia: 在自由生活环境下，很难准确估计能量摄入。我的体重多年来一直保持在2磅的波动范围内，这表明人体对能量储存的调节能力很强，即使能量输入和输出存在很大波动。我们讨论了人体如何调节能量储存，以及瘦素、食欲和能量消耗在其中的作用。我们还讨论了运动对体重减轻的影响，以及运动对食欲调节和饥饿激素（瘦素、生长素释放肽和GLP-1）的影响。我们还讨论了宏量营养素的组成如何影响能量消耗，以及个性化营养和公共卫生政策在指导营养习惯方面可能发挥的作用。我们还讨论了饮食中蛋白质的重要性、膳食数据收集的局限性以及人工智能如何改变营养科学。最后，我们讨论了我的热量限制（CR）兴趣是如何从Biosphere 2开始的，代谢效率在衰老中的作用以及CALERIE研究的目标。我们深入探讨了CALERIE研究，重点关注其在两年后的显著发现，包括持续的体重减轻、参与者的保留率等等。我们还讨论了热量限制对衰老特征的影响，以及将CR应用于普通人群的挑战，以及药物和运动模拟CR效果的潜力。我们还讨论了即将进行的一项比较热量限制与时间限制性饮食的研究，以及我对讨论的总结。

Deep Dive

Key Insights

Why is it difficult to measure energy intake in free-living environments?

In free-living environments, estimating energy intake is highly variable and often inaccurate due to the inability to precisely track every morsel of food consumed. This makes it challenging to obtain reliable data on caloric intake.

How does the body regulate energy storage despite inconsistent energy intake and expenditure?

The body has complex regulatory systems that manage energy storage, including signals from fat-free mass like skeletal muscle and organs. Leptin, a hormone from adipose tissue, helps defend against extreme weight loss but is less effective in preventing gradual weight gain due to leptin resistance.

What role does exercise play in weight regulation?

Exercise is less effective for weight loss due to compensatory mechanisms that often increase food intake. However, it is crucial for weight maintenance and overall metabolic health. Vigorous exercise can suppress appetite, while moderate exercise may slightly increase it.

How does the macronutrient composition of a diet affect energy expenditure?

Studies have shown that varying macronutrient composition under isocaloric conditions can influence energy expenditure. For instance, a ketogenic diet has been observed to increase energy expenditure initially, though this effect may diminish over time.

What are the challenges of conducting nutrition studies in real-life settings?

Real-life nutrition studies face challenges such as poor adherence to prescribed diets and difficulties in accurately measuring energy intake. These issues make it hard to translate controlled experimental findings into practical recommendations.

How might AI transform nutrition science?

AI could revolutionize nutrition science by providing precise tools to measure food intake through image recognition and other technologies. This would allow for more accurate tracking of macronutrient and caloric intake in free-living conditions.

What are the key findings from the CALERIE study on caloric restriction?

The CALERIE study found that 25% caloric restriction over two years led to sustained weight loss, improved cardiometabolic markers, and reduced oxidative stress. Participants also showed increased mitochondrial biogenesis and reduced inflammation, suggesting benefits for both primary and secondary aging.

What are the potential benefits of CR mimetics like GLP-1 agonists and metformin?

CR mimetics such as GLP-1 agonists and metformin may offer similar benefits to caloric restriction, including improved insulin sensitivity, reduced oxidative stress, and enhanced mitochondrial function, without the need for extreme dietary changes.

Why is time-restricted eating being studied as an alternative to caloric restriction?

Time-restricted eating is being explored as a potential method to achieve similar health benefits to caloric restriction without the need for significant caloric reduction. This approach may be easier for some individuals to adhere to long-term.

Chapters
Discusses the body's regulation of energy storage and the challenges of understanding the signals that control energy balance.
  • Leptin's role in defending against extreme weight loss but not in preventing gradual weight gain.
  • Signals from fat-free mass and potential new signals like FGF21 and myokines.
  • Population-level weight gain driven by environmental changes.

Shownotes Transcript

View the Show Notes Page for This Episode)

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Eric Ravussin is a world-renowned expert on obesity, metabolism, and aging whose pioneering research has shaped much of what we understand today about energy balance and caloric restriction. In this episode, Eric shares insights from his cutting-edge work on energy expenditure—a critical factor in understanding how our bodies regulate weight and appetite. He discusses methods for measuring energy output, energy balance, food intake, and appetite regulation, and explores key studies on macronutrient manipulation. Eric then delves into the CALERIE study on caloric restriction, highlighting insights related to biomarkers of both primary and secondary aging. The conversation also covers the potential of GLP-1 agonists to replicate these effects and looks ahead to how AI and technology could transform metabolic research in the coming years.

We discuss:

  • Eric’s background and current work metabolism and measuring energy expenditure [3:00];
  • The science behind metabolic chambers for measuring energy expenditure, and the complexities of indirect and direct calorimetry [8:00];
  • The body's regulatory systems for maintaining energy balance and the primary influence of energy intake on body weight [18:30];
  • The epidemic of obesity and a discussion of resting metabolic rate [24:45];
  • The impact of exercise, appetite, gut hormones, and eating patterns on weight regulation [28:45];
  • Experiments looking at how macronutrient composition affects energy expenditure [38:45];
  • The challenges of studying diet in real-life settings, the potential of personalized nutrition, and how public health policy could play a role in guiding nutritional habits [51:00];
  • The importance of protein in the diet, the limitations of dietary data collection, and how AI could potentially transform nutrition science [1:08:15];
  • How Eric’s interest in caloric restriction (CR) began with Biosphere 2, metabolic efficiency's role in aging, and goals of the CALERIE study [1:15:15];
  • The CALERIE study: exploring the real-world impact of caloric restriction [1:28:00];
  • Notable findings from the CALERIE study after two years: sustained weight loss, participant retention, and more [1:40:00];
  • The effect of caloric restriction on the hallmarks of aging [1:47:00];
  • The challenge of applying CR to the general population, the potential of drugs and exercise to mimic the effects of CR [1:55:45];
  • Upcoming study comparing caloric restriction to time-restricting eating, and Peter’s takeaways from the discussion [2:02:45]; and
  • More.

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