Browse the evidence

Epigenetic aging, as measured by the Skin&blood clock, is distinct from cellular senescence, telomere attrition, and genomic instability, but is associated with nutrient sensing, mitochondrial activity, and stem cell composition.

Epigenetic age is not a simple proxy for cellular damage or telomere length. Interventions that extend lifespan (like caloric restriction or rapamycin) slow epigenetic aging, while those that extend lifespan via other mechanisms (like NAD precursors or metformin in this specific context) may not. To influence epigenetic age, focus on nutrient sensing (mTOR pathway) and mitochondrial health, as these are mechanistically linked to the clock's ticking, distinct from DNA repair or telomere maintenance.

Women with diabetes have a 30% greater excess risk of cardiovascular disease (CVD) mortality compared to men with diabetes, driven largely by a higher risk of coronary heart disease (CHD) mortality.

Women with diabetes face a 30% higher relative risk of dying from heart disease than men with diabetes. This underscores the importance of rigorous cardiovascular monitoring and prevention for women, potentially requiring more aggressive management than standard protocols might imply.

Bariatric surgery induces significant lean body mass (LBM), fat-free mass (FFM), and skeletal muscle mass (SMM) loss, with approximately 55% of LBM loss occurring within the first 3 months post-surgery.

If you undergo bariatric surgery, expect to lose about 8 kg of lean body mass within the first year, with more than half of that loss happening in the first 3 months. This is not just fat loss; it includes muscle. To protect your metabolism and function, you must prioritize protein intake and resistance training immediately after surgery, not just focus on calorie restriction.

Consumer-grade wearable devices are not exempt from rigorous performance evaluation simply because they are marketed as 'research' or 'clinical' grade, as proprietary algorithms and hardware inconsistencies can still lead to significant errors.

Do not assume a device is accurate because it is 'clinical grade' or 'FDA cleared'. You must validate the specific device's sleep staging accuracy against PSG for your specific study population before using it for research conclusions.

Low-carbohydrate diets are not superior to higher-carbohydrate or low-fat diets for weight loss in adults with type 2 diabetes.

Do not expect low-carb diets to produce more weight loss than low-fat or high-carb diets if calories are matched. The choice of macronutrients should be based on preference and adherence, not expected superior weight loss results.

Metformin blunts increases in thigh muscle area and density resulting from progressive resistance training in older adults.

Metformin reduces the structural improvements (area and density) you get from weight training. This might be due to increased fat inside muscle cells. Talk to your doctor about your medication if muscle growth is a priority.

Metformin does not affect muscle fiber hypertrophy (cross-sectional area) or satellite cell abundance in response to progressive resistance training in older adults.

While metformin reduces overall muscle size, it doesn't seem to stop individual muscle fibers from growing. The issue may be related to fat content or other factors, not the fiber size itself.

Insulin resistance is a key pathophysiological factor in NAFLD, creating a bidirectional relationship where insulin resistance leads to liver fat accumulation and liver fat accumulation worsens insulin sensitivity.

Focus on improving insulin sensitivity. This involves managing weight, reducing refined carbs, and regular exercise. It helps both the liver and metabolic health.

Overall metrics (StDev, IS) overestimate sleep regularity when based on study lengths of 7 days or less, whereas consecutive metrics (SRI, CPD) are more stable but require larger sample sizes.

If you are analyzing sleep data for 7 days or less, be cautious with overall metrics like Interdaily Stability (IS) as they tend to overestimate regularity. Consecutive metrics like SRI are more stable for short durations but require larger sample sizes for group comparisons. For individual short-term assessments, prioritize SRI or CPD.

When total training volume is equated, increasing resistance training frequency per muscle group (from 1 to 3+ days/week) does not significantly or meaningfully increase muscle hypertrophy.

If you want to maximize muscle growth, focus on getting your total weekly sets in. How you split those sets across the week (1 day vs. 3 days) does not matter for hypertrophy, provided the total volume is the same. You can train each muscle group once a week or multiple times a week; choose the schedule that allows you to recover well and stick to your program.

The algebraic definition of Energy Availability (EA) has evolved to improve accuracy, with the current standard calculating EA relative to Lean Body Mass (LBM) rather than Total Body Mass (BM), subtracting non-exercise energy expenditure from gross exercise expenditure.

Use the current EA formula: (Energy Intake - Exercise Energy Expenditure) / Lean Body Mass. This is more accurate than using total body weight or gross exercise expenditure.

Lower socioeconomic status (higher Townsend Deprivation Index) significantly amplifies the genetic effect on BMI.

For those with high genetic risk for obesity, socioeconomic factors like deprivation can amplify the genetic effect on BMI. Addressing socioeconomic barriers may be as important as lifestyle changes in mitigating genetic risk.

Age-associated NAD+ decline is driven by two converging mechanisms: decreased biosynthesis (specifically reduced NAMPT expression) and increased consumption (specifically elevated PARP and CD38 activity due to DNA damage and aging).

NAD+ levels drop with age because your body makes less of it (due to lower NAMPT enzyme levels) and uses it up faster (due to DNA repair demands via PARP and other enzymes). This dual decline impairs cellular energy and repair mechanisms.

Higher body mass index (BMI), body weight, and waist circumference are inversely associated with cardiorespiratory fitness (CRF).

If you have a higher body weight or BMI, you may find your cardiorespiratory fitness (VO2max) is lower. This is a common physiological relationship. Addressing body weight through diet and activity can significantly improve your fitness levels, which in turn reduces your risk for chronic diseases.

Increasing age is inversely associated with cardiorespiratory fitness (CRF).

As you age, your cardiorespiratory fitness tends to decline. This is a common trend, but it is not a life sentence. You can counteract this decline by maintaining regular physical activity, which helps preserve your fitness levels and overall health as you get older.

Accurate dietary assessment using Food Frequency Questionnaires (FFQs) is insufficient for studying diet-microbiome relationships because they lack the specificity to link specific foods to microbial changes.

Most large-scale diet studies use simple questionnaires that may not accurately reflect what you ate. For microbiome research, these methods are often too vague to find specific links between foods and bacteria. More detailed food records are needed for accurate results.

Peptide 20, a GIPR/GLP-1R/GCGR tri-agonist, achieves balanced potency across all three receptors through specific structural modifications, including lipidation of K10P, which stabilizes binding and enhances receptor-mediated cAMP accumulation.

Peptide 20 is a complex drug that activates three metabolic receptors (GIP, GLP-1, Glucagon) simultaneously. Its effectiveness relies on specific chemical modifications (lipidation) that stabilize the drug's binding to these receptors, leading to significant improvements in blood sugar, weight, and glucose tolerance in animal models.

The unilateral exercise model (training one limb while keeping the contralateral limb as a control) significantly increases statistical power and reduces study costs compared to parallel-group or standard crossover designs by eliminating inter-subject variability and the need for washout periods.

For researchers, using a unilateral exercise model (training one limb while keeping the other as a control) is a highly efficient way to study muscle adaptations. It allows you to use fewer participants, reduces costs (fewer biopsies, less food provision), and eliminates the need for long washout periods between treatments, provided you are studying biochemical or histological outcomes rather than systemic or neuromuscular strength transfers.

The exact energy cost of skeletal muscle hypertrophy is unknown, and common textbook estimates based solely on tissue composition are likely inaccurate because they ignore the metabolic costs of synthesis, exercise, and adaptive thermogenesis.

Do not rely on textbook calculations for the exact energy cost of muscle gain. These estimates are likely inaccurate. Instead, use a conservative surplus (1,500-2,000 kJ/day) and adjust based on your progress. Individual responses vary greatly due to genetics and metabolic adaptations.

Glucagon emergency kits (subcutaneous, intramuscular, or intranasal) are the standard of care for rapidly reversing severe hypoglycaemia in Type 1 Diabetes, with newer formulations offering faster resolution and ease of use.

If you have Type 1 Diabetes, keep a glucagon emergency kit (like Baqsimi or Zegalogue) accessible. In a severe low blood sugar emergency where the person cannot eat or drink, this medication rapidly raises blood sugar by signaling the liver to release glucose. Newer nasal and auto-injector versions are easier to use and work faster than older injection kits.

Bariatric/metabolic surgery (BMS) is the most effective strategy for significant and sustained body weight reduction (14-25%) and reduces the risk of hypertension, diabetes, and mortality, but remains underused.

For extreme obesity (BMI ≥ 40 or ≥ 35 with comorbidities), bariatric surgery is the most effective treatment, producing 14-25% weight loss and significantly reducing the risk of heart disease, diabetes, and death. Despite its effectiveness, it is underused. If lifestyle and medication fail, discuss surgery with your doctor as a viable, life-saving option.

Leptin signaling via hypothalamic LepRbGlp1r neurons is the primary driver of food intake suppression, as ablating this receptor causes hyperphagic obesity without impairing energy expenditure.

This research identifies a specific brain pathway (LepRbGlp1r neurons) that leptin uses to tell you to stop eating. When this pathway is broken or ignored, you eat more regardless of how much energy you burn. This explains why some obesity treatments focus on mimicking these signals (like GLP-1 drugs) to restore the 'stop eating' signal rather than just forcing exercise.

Bariatric surgery is currently the most effective treatment for obesity in terms of mortality reduction and comorbidity resolution, but it is restricted to higher BMI classes and not suitable for all patients.

Bariatric surgery is the most effective treatment for obesity, significantly reducing mortality and type 2 diabetes risk, but it is generally reserved for patients with Class II or III obesity (BMI ≥ 35 or ≥ 40) and is not suitable for everyone due to surgical risks and access issues.

SGLT2 inhibitors provide significant cardiovascular and renal protection in patients with type 2 diabetes, heart failure, and chronic kidney disease, independent of glycemic control.

If you have Type 2 Diabetes along with heart failure or kidney disease, SGLT2 inhibitors (like Jardiance, Farxiga, or Trulicity's cousin) are now a standard, first-line treatment. They protect your heart and kidneys regardless of your blood sugar numbers. Discuss starting one with your doctor immediately, as guidelines strongly recommend it for this specific patient profile.