Browse the evidence

Chronic senescence, driven by accumulated cellular stress and defective clearance mechanisms, is a primary driver of biological aging and age-related diseases, whereas acute senescence serves beneficial roles in development and tissue repair.

Aging is not just 'wear and tear' but involves specific cells (senescent cells) that stop dividing but secrete inflammatory factors (SASP) that damage surrounding tissue. As we age, our immune system becomes less efficient at clearing these cells, leading to accumulation and disease. Current research focuses on 'senolytics' (drugs that kill these cells) to potentially improve health in the elderly, though no universally accepted biomarker or treatment is yet standard.

Weight gain occurring between age 30 years and menopause is associated with a greater increase in breast cancer risk than weight gain occurring between age 18 and 30 years, although the difference in risk magnitude between these two periods is not statistically significant.

While gaining weight between ages 18 and 30 is less risky than gaining weight after 30, both increase risk compared to staying thin. However, if you gained weight in your 20s, you are not doomed; losing that weight in your 30s or after menopause brings your risk down to levels similar to women who never gained weight. Prioritize preventing weight gain after age 30, but know that correcting it later is highly effective.

Dual fortification of salt with both iron and iodine is more effective than iodine-only fortification in reducing goiter prevalence in iron-deficient, goitrous children.

For communities with goiter and anemia, dual-fortified salt (iodine + iron) is superior to iodized salt alone.

High cumulative inflammatory load, specifically the combination of elevated Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α), is associated with significantly increased odds of short leukocyte telomere length (LTL) in older adults.

In older adults, high levels of specific inflammatory cytokines (IL-6 and TNF-α) are linked to shorter telomeres, a marker of biological aging. Standard CRP tests may not capture this risk. Managing chronic inflammation through lifestyle factors (diet, exercise, stress reduction) may help preserve telomere length, although this study is observational and does not prove causation.

Peripheral administration of long-acting GLP-1 receptor agonists (liraglutide and exendin-4) suppresses food intake and body weight through a combined mechanism involving both direct activation of central nervous system (CNS) GLP-1 receptors and activation of peripheral vagal afferent GLP-1 receptors.

Long-acting GLP-1 medications (like liraglutide) reduce appetite not just by signaling the stomach, but by also acting directly on the brain. This dual action is key to their effectiveness. If one pathway is blocked or less sensitive, higher doses may be needed to achieve the same result.

Insulin resistance (IR) is the primary mechanistic link connecting Metabolic Syndrome (MetS) to increased risk of Alzheimer's Disease (AD) and cognitive impairment, driven by impaired PI3K-Akt signaling, increased amyloid-beta (Aβ) production, and tau hyperphosphorylation.

Maintain metabolic health to protect your brain. If you have metabolic syndrome, obesity, or type 2 diabetes, your risk for cognitive decline is significantly higher due to insulin resistance. Prioritize interventions that improve insulin sensitivity (like exercise and diet) as they may directly protect against Alzheimer's pathology by preserving brain insulin signaling.

In the presence of a high-fat diet, fructose supplementation causes pronounced obesity, glucose intolerance, and hepatic insulin resistance, whereas glucose supplementation does not cause these metabolic deficits despite similar caloric intake.

If you are eating a high-fat diet, the type of sugar you consume matters significantly. Fructose (found in high-fructose corn syrup and table sugar) promotes obesity and insulin resistance, whereas glucose does not have the same negative impact on insulin signaling under these conditions. To mitigate metabolic risk, prioritize reducing fructose intake, especially when dietary fat is high.

Fructose uniquely upregulates the transcription factor SREBP1c and downstream fatty acid synthesis genes, leading to reduced liver insulin signaling, whereas glucose upregulates ChREBP and triglyceride synthesis without impairing insulin signaling.

Understanding how different sugars affect your liver can help you make better choices. Fructose drives fat production and insulin resistance through specific genetic pathways (SREBP1c), while glucose may actually support insulin sensitivity. If you consume high-fat meals, minimizing fructose (soda, candy) is more critical for metabolic health than avoiding glucose sources.

Roux-en-Y gastric bypass (RYGBP) surgery induces an exaggerated postprandial secretion of Peptide YY (PYY) and suppresses fasting bioactive (octanoylated) ghrelin levels, mechanisms that contribute to sustained weight loss and maintenance by promoting early satiety and reducing hunger.

For individuals with morbid obesity, Roux-en-Y gastric bypass surgery alters gut hormones to favor weight loss maintenance. Specifically, it triggers a strong release of Peptide YY (PYY) after eating, which signals fullness to the brain, and lowers active ghrelin (the hunger hormone). This hormonal shift helps patients feel full sooner and stay full longer, making it easier to maintain weight loss compared to dieting alone.

Unlike diet-induced weight loss, Roux-en-Y gastric bypass (RYGBP) does not trigger a compensatory increase in fasting ghrelin levels, thereby avoiding the hormonal drive for hunger typically associated with caloric restriction.

When you lose weight through dieting, your body naturally increases hunger hormones (ghrelin) to make you eat more. Roux-en-Y gastric bypass surgery avoids this biological backlash. Patients maintain lower levels of active ghrelin, meaning they do not experience the intense hunger spikes that often cause diet failures, making long-term weight maintenance easier.

Prescribing a free, widely-used smartphone calorie-tracking app (MyFitnessPal) to overweight primary care patients for 6 months does not produce significant weight loss compared to usual care.

Giving patients a calorie-tracking app like MyFitnessPal is not a substitute for counseling or motivation. In this study, most users stopped using the app within a month because they found it tedious or were too busy. This intervention did not lead to weight loss. Clinicians should assess a patient's readiness and willingness to perform daily self-monitoring before prescribing such tools, as the app alone is insufficient for most patients.

Obesity and excess caloric intake lead to immune dysfunction by causing leptin resistance and downregulating immune responsiveness, increasing susceptibility to infections.

Maintaining a healthy weight is crucial for immune function. Obesity is linked to reduced white blood cell activity and increased inflammation. While weight loss is beneficial, understand that the biological changes (like leptin resistance) take time to reverse, and immune health is also influenced by the quality of fats and sugars you consume.

Mitochondrial dysfunction, characterized by impaired oxidative capacity and increased reactive oxygen species (ROS), promotes insulin resistance in skeletal muscle by causing the accumulation of lipotoxic lipid intermediates (diacylglycerol and ceramide) that inhibit insulin signaling.

For those with insulin resistance or T2DM, focusing on interventions that support mitochondrial health (like exercise which upregulates PGC-1α) may be more effective than focusing solely on caloric restriction. The paper suggests that boosting mitochondrial function can improve insulin sensitivity, potentially by reducing toxic lipid buildup in muscles.

Obesity-induced adipose tissue hypertrophy triggers a proinflammatory state (via TNF-α, IL-6, MCP-1, and reduced adiponectin) that directly causes endothelial dysfunction by disrupting the balance of vasodilators (NO) and vasoconstrictors, initiating atherosclerosis and cardiovascular disease.

Excess body fat is not just stored energy; it acts as an active organ that releases inflammatory chemicals (like TNF-α and IL-6) and reduces protective ones (adiponectin). This chemical imbalance damages the inner lining of your blood vessels (endothelium), leading to stiffness, plaque buildup, and heart disease risk. Managing weight and inflammation is critical to protecting your vascular health.

In older women, the use of supplemental iron is associated with a significantly increased risk of total mortality, with risk increasing in a dose-dependent manner.

If you are an older woman, do not take iron supplements unless a blood test confirms you have a deficiency. This study found that taking iron supplements was linked to a higher risk of death, and the risk got worse the more iron you took. Talk to your doctor about getting your iron levels checked before continuing any iron supplements.

In older women, the use of multivitamins, vitamin B6, folic acid, magnesium, zinc, and copper is associated with an increased risk of total mortality.

If you are an older woman, be aware that taking multivitamins, vitamin B6, folic acid, magnesium, zinc, or copper might be linked to a higher risk of death. This study found that women who took these supplements had a slightly higher chance of dying during the follow-up period. You should discuss with your doctor whether you really need these supplements.

Fetal exposure to nutrient restriction programs a 'thrifty phenotype' that increases susceptibility to type 2 diabetes and cardiovascular disease when the individual encounters an environment of nutritional abundance.

If you were born small or in a low-resource environment, your body is biologically programmed to store energy efficiently. When you have access to abundant food, this 'thrifty' programming makes you highly susceptible to weight gain and diabetes. You must be proactive about diet and activity, as your body will fight harder to store fat than someone with a different early-life history.

Rising income levels in developing countries lead to a 'nutrition transition' characterized by sedentary lifestyles and high-calorie diets, causing a rapid increase in childhood obesity and type 2 diabetes.

As countries develop and people earn more, they often consume more processed foods and move less. This leads to rapid increases in childhood obesity and diabetes. To counter this, communities and families must prioritize physical activity and healthy food choices even as incomes rise.

Perivascular adipose tissue (PVAT) and epicardial adipose tissue (EAT) exert local paracrine effects on cardiovascular health, functioning as protective in lean states via adiponectin and prostacyclin release, but becoming pathogenic in obesity by shifting to a pro-inflammatory state that promotes vasoconstriction, smooth muscle proliferation, and atherosclerosis.

Epicardial and perivascular fat are biologically active tissues that influence heart health. In lean individuals, they release protective substances like adiponectin that keep blood vessels flexible and healthy. In obesity, these depots become inflamed, releasing harmful substances that stiffen arteries and promote plaque buildup. While imaging these fats is useful for research, current evidence suggests that overall visceral fat reduction (via weight management) is the most effective way to mitigate these risks, as local fat measurements do not significantly add to risk prediction beyond standard visceral fat metrics.

A flatter diurnal slope in salivary cortisol (characterized by elevated evening levels rather than depressed morning levels) is associated with a significantly increased risk of cardiovascular mortality in middle-aged adults.

This research suggests that how your cortisol levels drop throughout the day is more important for heart health than how high they are in the morning. Specifically, a 'flat' slope—where evening cortisol remains elevated rather than declining—predicts higher cardiovascular risk. While you cannot directly 'dose' cortisol, this pattern is often linked to chronic stress, poor sleep, or fatigue. Prioritizing stress reduction techniques and ensuring adequate sleep duration may help normalize this diurnal rhythm, potentially lowering cardiovascular risk.

The Body Checking Questionnaire (BCQ) is a valid, reliable, and multidimensional self-report measure that distinguishes between individuals with eating disorders and healthy controls, as well as between different types of eating disorders.

If you are concerned about body checking behaviors, a structured self-report questionnaire like the BCQ can help identify specific patterns (e.g., checking weight vs. checking shape). This tool is validated for distinguishing between different types of eating disorders and can be a useful first step in clinical assessment, though it should be interpreted by a professional.

The combination of GH and IGF-I attenuates the hypoglycemia caused by IGF-I alone while maintaining better glucose tolerance than GH alone.

When treating catabolism, using IGF-I alone can dangerously lower blood sugar, often requiring dose reductions. Adding Growth Hormone to the regimen stabilizes blood glucose levels, preventing these lows without causing the high blood sugar typically associated with GH alone. This balance makes the combination therapy metabolically safer and more sustainable than IGF-I monotherapy.

The combination of GH and IGF-I increases serum IGF-I concentrations and stabilizes the IGF-I pool by inducing IGFBP-3 and Acid-Labile Subunit (ALS), leading to greater anabolic efficacy.

The combination therapy works partly by increasing the amount of stable IGF-I in the blood. GH stimulates the production of binding proteins (IGFBP-3 and ALS) that protect IGF-I from rapid breakdown, allowing it to work more effectively and for longer periods than IGF-I alone.

Interventions targeting only Physical Activity (PA) or combined PA and Sedentary Behavior (PA/SB) do NOT significantly reduce sedentary time in adults.

Simply exercising more or combining exercise with sitting reduction advice does not necessarily reduce your total sitting time. To reduce sitting, you need specific strategies focused on breaking up sitting time, not just adding exercise.