Metabolism

Metabolism and aging: what actually changes

Metabolism is the sum of every chemical reaction keeping you alive. It converts food into ATP, builds and repairs tissue, synthesizes hormones, and clears cellular waste. The common belief that metabolism "breaks" in your 30s or 40s turns out to be wrong. A landmark 2021 study in Science analyzed over 6,600 people across 29 countries and found that total energy expenditure, adjusted for body size and composition, stays remarkably stable from age 20 through 60. The real decline only begins after 60, at roughly 0.7% per year ^[1]. What does change earlier is body composition: muscle mass drops, fat mass rises, and physical activity decreases. These shifts, not some metabolic clock, account for most of the perceived slowdown.

Metabolic flexibility: the ability to switch fuels

Metabolic flexibility is the capacity to efficiently toggle between burning glucose (in the fed state) and burning fatty acids (during fasting or exercise). A metabolically flexible person transitions smoothly from glycolysis to beta-oxidation and ketogenesis depending on fuel availability. Chronic overfeeding, sedentary behavior, and constantly elevated insulin levels degrade this flexibility over time, locking cells into glucose dependence even when fat stores are abundant ^[2].

Restoring metabolic flexibility is one of the most actionable targets in metabolic health. Time-restricted eating, periodic fasting, and zone 2 aerobic training all push the body to practice fuel switching. Continuous glucose monitoring data shows that individuals with high metabolic flexibility have smaller post-meal glucose spikes and faster returns to baseline, reflecting better insulin signaling and substrate handling.

Insulin sensitivity and metabolic syndrome

Insulin orchestrates nutrient partitioning: where glucose goes, whether fat gets stored or burned, and how amino acids are used. When cells stop responding efficiently to insulin, blood sugar rises, the pancreas produces more insulin to compensate, and a vicious cycle begins. This is insulin resistance, and it's the central feature of metabolic syndrome. Metabolic syndrome is defined by having three or more of five criteria: elevated fasting glucose (100+ mg/dL), high blood pressure (130/85+ mmHg), high triglycerides (150+ mg/dL), low HDL cholesterol, and large waist circumference ^[3].

The prevalence is staggering. Global metabolic syndrome rates rose from about 12% in 2000 to over 30% by 2023 ^[4]. In the US, roughly 40% of adults qualify. Optimal targets for longevity-focused individuals go well beyond "normal" ranges: fasting insulin below 5 microIU/mL, HOMA-IR below 1.0, HbA1c below 5.0%, and a triglyceride-to-HDL ratio below 1.0.

Mitochondrial health and energy production

Mitochondria generate roughly 90% of cellular ATP through oxidative phosphorylation. With age, mitochondrial number declines, their DNA accumulates mutations, and electron transport chain efficiency drops. This mitochondrial dysfunction contributes to fatigue, sarcopenia, neurodegeneration, and accelerated aging ^[5]. The process also drives a Warburg-like metabolic shift in aging cells, where glycolysis takes over even when oxygen is available.

Strategies that support mitochondrial biogenesis include cold exposure (which activates PGC-1alpha), high-intensity interval training, and zone 2 aerobic exercise. Supplements with evidence for mitochondrial support include CoQ10, NAD+ precursors like NMN and NR, and pyrroloquinoline quinone (PQQ). The combination of regular exercise and adequate sleep provides the strongest foundation for mitochondrial health.

NEAT: the overlooked metabolic lever

Non-exercise activity thermogenesis (NEAT) includes every calorie burned through daily movement that isn't formal exercise: walking, standing, fidgeting, cooking, cleaning. NEAT can vary by up to 2,000 kcal per day between individuals and is often a bigger contributor to total energy expenditure than structured exercise ^[6]. Office workers who stand and walk regularly throughout the day can burn 350+ more calories than those who sit continuously. NEAT also decreases automatically during caloric restriction, which partly explains why weight loss plateaus occur.

Practical strategies for metabolic optimization

Building metabolic resilience requires working on multiple fronts simultaneously. Prioritize adequate protein intake (1.6-2.2 g/kg lean body mass) to maintain skeletal muscle, the body's largest metabolic organ. Combine zone 2 endurance training with resistance training at least 3 times per week. Even one night of poor sleep can impair glucose tolerance by up to 40%, making consistent sleep a non-negotiable metabolic intervention ^[7]. Increase daily NEAT through walking, standing desks, and active commuting. Consider continuous glucose monitoring to identify your personal glycemic responses and fine-tune meal composition and timing.

Key metabolic biomarkers to track

• Fasting glucose (optimal: 72-85 mg/dL) and HbA1c (optimal: below 5.0%) for glycemic control
• Fasting insulin (optimal: below 5 microIU/mL) as an early marker of insulin resistance
• Triglyceride-to-HDL ratio (optimal: below 1.0) reflecting overall metabolic health
• Uric acid (optimal: 3.5-5.5 mg/dL) as an indicator of metabolic stress
• VO2 max and lactate threshold as functional markers of mitochondrial capacity