Increasing Healthspan

 Eric Topol, a prominent figure in translational medicine and the author of Super Agers, underscores that extending healthspan and improving longevity hinges significantly on a comprehensive approach to "Lifestyle+" factors. This term, as Topol defines it in his work, extends beyond the traditional understanding of diet, exercise, and sleep, to include environmental conditions, socioeconomic status, and social well-being. He highlights that while many of these interventions may seem "low-tech," our understanding of their profound impact has evolved dramatically, collectively offering benefits that are hard for any single drug or intervention to match.

Here are the key longevity factors discussed:

• Dietary Choices

  • Ultra-Processed Foods (UPFs): Topol's book Super Agers and his Ground Truths newsletter extensively detail how ultra-processed foods are like "alien, industrially produced, unnatural substances" that are detrimental to health. These foods, often found in the middle aisles of grocery stores, contain additives and industrial ingredients, and undergo physical changes that maximise digestibility, leading to spikes in blood glucose and insulin. Eating UPFs is associated with increased calorie intake, weight gain, a significantly heightened risk of cardiovascular and metabolic diseases, insulin resistance, systemic inflammation, and various cancers. Consuming more than four servings per day is linked to a 62 percent increase in all-cause mortality. Topol strongly advises restricting UPFs to the lowest possible level for healthy aging, and points out the lack of US guidelines compared to other countries, partly due to the influence of "Big Food" on regulatory bodies.
  • "Good Food" and Healthy Eating Patterns: In stark contrast, Topol advocates for "healthy eating," which is consistently associated with lower cardiovascular risk and reduced all-cause mortality, showing a dose-response relationship for various ailments. This involves consuming fruits, vegetables, legumes, whole grains, nuts, seeds, and healthy fats like olive oil and avocados, as well as fatty fish rich in omega-3s. These foods are excellent sources of dietary fibre, which slows digestion, reduces glucose spikes, and helps lower cholesterol, countering the pro-inflammatory effects of the Western diet.
  • Mediterranean Diet: The Mediterranean diet is singled out for its robust support from multiple randomised trials and observational studies, showing associations with reduced mortality from any cause, including cardiovascular diseases, cancer, and neurodegenerative diseases. Its components, detailed by Topol, include daily olive oil, frequent servings of fruits, vegetables, fish, and legumes, with discouraged consumption of soda, commercial sweets, spread fats, and red/processed meats.
  • Macronutrients: The type of macronutrient matters.
    • Carbohydrates: The concept of "carbotoxicity" highlights risks from excessive intake. High-quality carbs, such as resistant starch and dietary fibre (25-30 grams per day), are linked to reduced all-cause and cardiovascular mortality, type 2 diabetes, and colon cancer. Low-quality, fast-digesting carbs like refined grains are associated with increased cardiovascular deaths.
    • Protein: The recommended daily allowance (RDA) for protein may be underestimated for older individuals, who likely need higher intake to prevent sarcopenia (age-related muscle loss). However, Topol notes that excessive high-protein diets (over 1.5 g/kg) can produce pro-inflammatory metabolites and promote atherosclerosis, especially leucine-rich animal proteins.
    • Fats: The quality of fat is crucial, with monounsaturated and polyunsaturated fats associated with more favourable longevity data, and a shift from saturated to plant-based unsaturated fats reducing the risk of cardiovascular disease and type 2 diabetes. Dairy products, a source of saturated fat, show mixed evidence, with some studies linking greater whole-fat dairy intake (especially unsweetened yogurt and hard cheese) to reduced cardiovascular disease and type 2 diabetes risks.
  • Sweeteners and Salt: High sugar consumption, especially from sugar-sweetened beverages, is clearly detrimental, linked to increased all-cause, cardiovascular, and cancer-related mortality. Artificial sweeteners have conflicting reports, with some showing links to cardiovascular disease and impaired glucose regulation, though generally less worrisome than high sugar. Moderate salt consumption (1-2 teaspoons or 2-5 grams of sodium per day) may not be problematic, but higher intake increases cardiovascular risk and can affect cognitive function.
  • Caffeine and Alcohol: While coffee consumption (around four cups per day) has been consistently associated with reduced mortality for various conditions and a lack of hazard for heart rhythm disturbances, Topol cautions that definitive cause-and-effect proof is still lacking. For alcohol, the evidence is less blurry: moderate to heavy drinking offers no benefit, and even light intake (e.g., two drinks per week) shows a J-curve relationship with potential small benefit but rapidly increasing risks beyond that level, especially for cardiovascular disease and cancer.
  • Red Meat and Plant-Based Diets: Processed meats are classified as carcinogenic, and unprocessed red meats as "probably carcinogenic" by the WHO. Higher red meat intake, particularly processed red meat, is consistently linked to increased all-cause mortality, cardiovascular, and cancer risks. Plant-based diets, in contrast, are associated with a lowered risk of type 2 diabetes, all-cause and cardiovascular mortality, and cancer, and can positively modulate the gut microbiome.
  • Personalised Nutrition: Topol acknowledges the naive idea of a one-size-fits-all diet, emphasising individual uniqueness in genomics, metabolism, and gut microbiome. The "AI Diet" concept, using continuous glucose monitoring (CGM) and machine learning to analyze vast datasets including gut microbiome, aims to create tailored nutritional advice to avoid glucose spikes and improve health outcomes.

• Exercise

  • The "Most Potent Medical Intervention": Eric Topol and Euan Ashley highlight exercise as the single most effective medical intervention known, having profound positive impacts across virtually all organ systems. This includes favourable adaptations in the cardiovascular system, brain, pancreas, skeletal muscle, gastrointestinal tract, liver, adipose tissue, gut microbiome, and immune system.
  • Comprehensive Benefits: Exercise provides significant prevention against cardiovascular disease (up to 50% reduction), many cancers (up to 50% reduction), and offers positive effects on mental health, pulmonary health, GI health, bone health, and muscle function. It also improves insulin sensitivity and mitochondrial function, and suppresses inflammation.
  • Dose-Response and Types: Even small amounts of exercise are beneficial; Euan Ashley states that "one minute of exercise bought you five minutes of extra life," increasing to "seven or eight minutes" for high-intensity exercise. While aerobic exercise is crucial, Topol, now understanding its importance, stresses the need for strength, resistance, and balance training as well. Muscle mass and strength decline significantly with age, and resistance training offers benefits like reduced all-cause mortality, less visceral fat, better sleep, and improved bone density and mental well-being.
  • Steps and Intensity: While 10,000 steps a day is a common goal, studies show benefits starting at much lower levels (e.g., 2,700 steps/day for older women). The focus should be on dedicated sessions that sustain an increased heart rate, distinguishing it from fragmented physical activity. Topol encourages people to "push it a bit" with higher intensity exercise for added benefits, provided there are no underlying medical risks.
  • Mitigating Sedentary Lifestyles: Prolonged sitting is linked to higher all-cause and cardiovascular mortality, with increased physical activity helping to mitigate these detrimental effects.
  • Individualisation: Technologies like those developed by Euan Ashley's company, Svexa, are working towards individualising training through data and AI to optimise performance and reduce injury for athletes.

• Sleep

  • Brain Waste Clearance (Glymphatics): Topol highlights that sleep is a "non-negotiable biological state" crucial for the brain's "glymphatic pathway," which clears metabolic waste products like β-amyloid, a precursor to Alzheimer's disease. Impaired waste clearance has been documented after even a single night of sleep deprivation.
  • Optimal Duration and Impact: Approximately seven hours of sleep is considered optimal. Both insufficient (six hours or less) and excessive (more than eight hours) sleep are associated with cognitive and mental health decline, unfavourable brain structure changes, and increased all-cause and cardiovascular mortality. Poor sleep is prospectively linked to the risk and progression of Alzheimer's disease.
  • Age-Related Changes and Challenges: Older adults often experience less deep, non-REM sleep (essential for health, memory, and cognition), more fragmented sleep, and regression of circadian timing.
  • Promoting Healthy Sleep: Key recommendations include maintaining a consistent sleep pattern daily, regular exercise and meals (with adequate separation from bedtime), a cool, dark, quiet bedroom, and avoiding blue light from electronic devices. Topol notes that commonly used sleep medications like Ambien can suppress glymphatic flow and are linked to heightened Alzheimer's risk, urging a need for safer, more effective solutions. Sleep apnea, a common sleep disruption, is also of significant importance due to its association with cardiovascular and metabolic diseases.

• Environmental Toxins

  • Pervasive Exposure: Topol underscores that environmental toxins are a critical, often underestimated, aspect of "Lifestyle+".
  • Air Pollution: Particulate matter (PM2.5, PM10), nitrogen dioxide, and ozone are major contributors to global disease burden, linked to increased all-cause, cardiovascular, and respiratory mortality, as well as cognitive decline and type 2 diabetes, even at levels below national air quality standards.
  • Microplastics and Nanoplastics (MNPs): These "alien" substances are ubiquitous in our environment, food, air, and water, carrying thousands of chemicals known to be carcinogenic, neurotoxic, and endocrine-disrupting. Topol reports deeply concerning findings: MNPs have been found in arteries, blood clots, liver, gut, lungs, placentas, testes, and even the brain. Their presence in atherosclerotic plaque is linked to a 4.5-fold heightened risk of heart attack, stroke, or death, and brain MNP concentrations are significantly higher in people with dementia. He points out that the unchecked buildup of plastics and our pervasive use of disposable items demand urgent attention and a significant reduction in plastic production.
  • "Forever Chemicals" (PFAS): These man-made chemicals are widespread, found in water and numerous products, and are linked to kidney and testicular cancer, obesity, high blood pressure, high cholesterol, and immune system damage.
  • Other Toxins: Secondhand smoke, radon (linked to lung cancer and stroke), pesticides (associated with various cancers and cognitive impairment), noise pollution (increasing stress hormones, inflammation, and cardiovascular risk), ionising radiation from medical imaging, and exposure to certain metals also pose significant health hazards. Topol suggests that the rise in cancers among younger adults may be attributable to these environmental factors.

• Social and Socioeconomic Factors

  • Social Isolation and Loneliness: A systematic review of 90 cohort studies revealed an association between loneliness and a 32 percent increased all-cause mortality, a 34 percent rise in cardiovascular mortality, and a 24 percent higher cancer-related mortality. Topol emphasizes assessing and countering these factors.
  • Socioeconomic Status (SES): Topol highlights SES as a pivotal, independent risk factor for premature mortality, impacting health as much as smoking or type 2 diabetes. Lower SES is disproportionately associated with poorer diet, less sleep, more air pollution, and less physical activity. Addressing these inequities, including combating "food deserts" and food insecurity, is crucial for population-wide healthspan improvement.

• Advanced Diagnostics for Tracking Longevity

  • p-Tau217 Biomarker: Topol describes this blood test as a "breakthrough" in neurology for accurately predicting Alzheimer's disease (AD) over 20 years in advance, well before symptom onset. Crucially, p-Tau217 levels are dynamic and can respond to interventions like exercise, suggesting its utility in tracking treatment response and guiding lifestyle modifications to prevent or delay AD.
  • Proteomic Organ Clocks: Drawing on work by Tony Wyss-Coray, Topol explains how thousands of plasma proteins can be measured to calculate "organ age gaps," identifying individuals whose organs are physiologically older than their chronological age. These organ clocks can predict future disease risks (e.g., accelerated heart aging linked to heart failure, brain aging to Alzheimer's) and show sensitivity to lifestyle interventions like alcohol, exercise, and diet. This emerging field offers a promising avenue for predicting and tracking organ-specific aging and health.

In summary, Topol’s work in Super Agers and Ground Truths emphasizes that achieving and extending healthspan and longevity requires a holistic and active engagement with these interconnected "Lifestyle+" factors. While cutting-edge technologies offer new ways to monitor our health, the fundamental pillars of a healthy diet, regular exercise, adequate sleep, minimal exposure to environmental toxins, and robust social connections remain paramount.