Diet: The Cornerstone of Healthy Aging

Eric Topol, a leading figure in translational medicine and the author of Super Agers, comprehensively defines healthy aging not merely as extending lifespan but as maximising healthspan—the number of years lived in good health, free from chronic disease and significant impairment. His framework, which he calls "Lifestyle+", underscores that achieving this involves a multifaceted approach that extends beyond traditional healthy habits (diet, exercise, sleep, and avoiding tobacco and excessive alcohol) to include critical environmental, social, and even technological factors. Topol contends that many healthy years can be added to our lives by addressing these interconnected elements, often without expensive, high-tech medical interventions.

Here's a breakdown of the key components of healthy aging as discussed by Topol:

Diet: The Cornerstone of Healthy Aging

Diet is highlighted as a paramount factor, with poor dietary patterns linked to a staggering 22% of all global deaths, surpassing other major health risks like tobacco.

• Ultra-Processed Foods (UPFs): Topol describes UPFs as "alien, industrially produced, unnatural substances; they're not even food". These foods, rich in additives and industrial ingredients, undergo physical changes during manufacturing that maximise digestibility and accelerate glucose and insulin spikes. Randomised trials show UPFs lead to overeating (an extra 500 calories per day) and weight gain. They are strongly associated with a markedly heightened risk of cardiovascular and metabolic diseases, including an 80% elevated risk of metabolic syndrome, 40% higher risk of type 2 diabetes, 23% increased risk of hypertension, 55% risk of obesity, and 66% risk of cardiovascular death. Furthermore, more than four servings per day of UPFs are linked to a 62% increase in all-cause mortality, as well as higher risks of cancer, sleep disorders, and dementia. Topol strongly advises restricting UPFs to the lowest level possible for healthy aging. He notes the significant influence of "Big Food" in hindering public health guidelines against UPFs in the United States.
• Sugary Beverages: These are the primary source of added sugar and are associated with a 24% increased all-cause mortality, and heightened cardiovascular and cancer-related mortality. Drinking over two litres per week can more than triple the risk of atrial fibrillation.
• Excessive Salt Intake: While moderate consumption is acceptable, exceeding 5 grams of sodium per day (the average American intake is about 3.5 grams) is linked to increased cardiovascular risk and can reduce blood flow to the brain, potentially increasing cognitive impairment risk.
• Harmful Carbohydrates: Both very low (<40%) and very high (>70%) carbohydrate intake are associated with increased all-cause mortality. Low-quality, fast-digesting carbohydrates (refined grains, potato products) cause high glycemic loads and are linked to a more than 25% increase in cardiovascular deaths.
• Red Meat and Processed Meats: Processed meats are classified as "carcinogenic to humans" by the World Health Organization, while unprocessed red meats are "probably carcinogenic". Regular consumption of ultra-processed red meat is linked to a 14% higher risk of dementia. Mechanistically, red meat can reduce beneficial short-chain fatty acids (SCFAs), induce a "leaky" gut, and lead to the production of trimethylamine N-oxide (TMAO), which is strongly associated with cardiovascular disease and potentially colon cancer.
• Beneficial Dietary Patterns ("Good Food"): Topol advocates for "healthy eating" which includes fruits, vegetables, legumes, whole grains, nuts, seeds, healthy fats (like olive oil and avocados), and fatty fish rich in omega-3 fatty acids. These foods collectively provide dietary fibre, which slows digestion, lessens glucose spikes, and reduces cholesterol. The Mediterranean diet is particularly well-supported by evidence, with multiple randomised trials showing significant reductions in all-cause mortality, cardiovascular diseases, cancer, and neurodegenerative diseases. A plant-based diet has been linked to a 23% lowered risk of type 2 diabetes and substantial protection from all-cause and cardiovascular deaths.
• Personalised Nutrition: The "AI Diet" is an emerging field, leveraging extensive data on individual genomics, metabolism, gut microbiome, and lifestyle to determine optimal food intake. Continuous glucose monitors (CGMs) are a step towards this, revealing individual glucose spikes in response to food, exercise, and sleep.

Exercise: The Potent Medical Intervention

Eric Topol and his colleague Euan Ashley, a co-leader of the MoTrPAC consortium, view exercise as perhaps the single most potent medical intervention known, with profound, sweeping benefits across nearly every organ system.

• Multi-system Benefits: Regular exercise leads to favourable adaptations in the cardiovascular system, brain, pancreas, skeletal muscle, gastrointestinal tract, liver, adipose tissue, gut microbiome, and peripheral blood vessels. It enhances insulin sensitivity, protects against atherosclerosis, and improves cardiovascular function by reducing blood lipids, increasing lipid oxidation, and lessening body-wide and brain inflammation.
• Immune System Enhancement: The MoTrPAC study, for instance, showed the immune system is a commonly upregulated system with regular exercise, with significant changes observed in immune genes in various tissues, including the small intestine. This strengthened immune response is believed to be a key mechanism behind exercise's ability to reduce the risk of certain cancers.
• Mental Health: Exercise has dramatic positive effects on mental health, with studies showing it can be more effective than antidepressant drugs for depression and anxiety. It promotes a "runner's high" through the release of opioids and positively impacts brain chemistry.
• Cancer Protection: Exercise is associated with a 50% reduction in the risk of many cancers. Studies have shown that increased exercise can improve survival rates even for aggressive cancers like pancreatic cancer.
• "Hormesis" and Stress Resilience: Exercise acts as a recurrent stressor, conditioning the body to deal with stress at a cellular level, as reflected by the prominence of the heat shock response across multiple tissues.
• Intensity and Type: Both aerobic and strength/resistance training are crucial for healthy aging. Topol, reflecting on his own practice, now emphasises both. While all movement is beneficial, higher-intensity exercise may offer additional longevity benefits. Flexibility and balance training are also important, particularly for older adults.
• Dose-Response: Even short bursts of activity are beneficial; for example, one minute of exercise may add five minutes of life, increasing to seven or eight minutes for high-intensity exercise. Benefits for all-cause mortality are seen with just 2,700 steps/day, plateauing around 7,500-8,800 steps/day, although the widely cited 10,000 steps per day has gained further support from recent studies. The World Health Organization recommends at least 150 minutes/week of moderate physical activity or 75 minutes/week of vigorous activity, plus muscle-strengthening activities twice a week.
• Individualised Exercise: Advances in data and AI, as seen in companies like Svexa (co-founded by Euan Ashley), are enabling the individualisation of training to optimise performance and reduce injury for athletes, a concept that may extend to the general population.

Sleep: The Brain's Waste Clearance System

Sleep is a non-negotiable biological state essential for maintaining human life, paralleling needs for air, food, and water.

• Brain Waste Clearance (Glymphatic System): During non-REM sleep, the brain's glymphatic system efficiently clears metabolic waste products, including toxic proteins like β-amyloid, a precursor to Alzheimer's disease. A single night of sleep deprivation can significantly increase β-amyloid accumulation.
• Optimal Duration: Studies from the UK Biobank suggest that about seven hours is the optimal duration of sleep. Both insufficient (less than 7 hours) and excessive (more than 8 hours) sleep are associated with cognitive decline, poorer mental health, and heightened all-cause and cardiovascular mortality.
• Aging and Sleep Quality: As we age, deep sleep (non-REM stage 3) significantly decreases, and sleep becomes more fragmented. This impairs the efficiency of the glymphatic system, leading to the accumulation of metabolic waste and contributing to brain aging and neurodegenerative diseases.
• Promoting Healthy Sleep: Strategies include maintaining a regular bedtime and wake-up schedule, regular exercise, avoiding late-night eating, creating a cool and dark bedroom, avoiding blue light from electronic devices, and treating sleep apnea. Paradoxically, some common sleep aids like Ambien can suppress brain waste disposal.

Environmental Toxins: The Silent Threat

Topol's "Lifestyle+" expands to acknowledge that our environment is a major, often overlooked, contributor to chronic disease and reduced healthspan.

• Air Pollution: Identified as the leading contributor to the global disease burden, even short-term exposure is linked to increased mortality. Chronic exposure to fine particulate matter (PM2.5) is associated with 20% of type 2 diabetes cases, cognitive decline, reduced immune response, and increased blood pressure, primarily through body-wide and brain inflammation, compromised immune function, and oxidative stress.
• Microplastics (MNPs) and Nanoplastics: These ubiquitous particles carry thousands of chemicals and have been found in human arteries, brains, blood clots, liver, gut, lungs, placentas, and testicles. The presence of MNPs in atherosclerotic plaque was associated with a 4.5-fold increased risk of all-cause mortality, heart attack, and stroke. A recent study found MNP concentration in the brain to be 7-30 times greater than in the liver or kidneys, and significantly higher in individuals with dementia. Animal models show MNPs can cross the blood-brain barrier, activate the immune system, disrupt blood flow, and cause clots, leading to neurological abnormalities. They are linked to various cancers, cognitive decline, cardiometabolic disease, and infertility.
• Perfluorinated and Polyfluorinated Alkyl Substances (PFAS): These "forever chemicals" are prevalent in water, food, and consumer products. High exposure is linked to kidney and testicular cancer, obesity, increased blood pressure, high cholesterol, inflammatory bowel disease, and damage to the thyroid, liver, brain, and immune system.
• Other Toxins: Secondhand smoke, radon, pesticides, and chronic noise pollution also contribute to chronic diseases like heart disease, stroke, type 2 diabetes, cancers, cognitive impairment, and autoimmune conditions.
• Ionising Radiation and Metals: Excessive medical imaging (CT scans, nuclear imaging) and exposure to certain metals (cadmium, tungsten, uranium, cobalt, copper, zinc) are associated with increased cancer risk and cardiovascular disease.

Social and Socioeconomic Factors

Beyond individual lifestyle, social connections and socioeconomic conditions play a critical role.

• Loneliness and Social Isolation: A systematic review of 90 cohort studies found an association between loneliness and a 32% increased all-cause mortality, 34% rise in cardiovascular mortality, and 24% higher cancer-related mortality.
• Socioeconomic Status: Topol highlights that socioeconomic status is an independent risk factor for premature mortality, on par with smoking or type 2 diabetes. Lower socioeconomic status is disproportionately associated with less healthy diets, poorer sleep, more air pollution exposure, and less physical activity.

Tracking Healthy Aging with Emerging Technologies

Topol also explores how new technologies are enhancing our ability to measure and track healthspan.

• Proteomic Organ Clocks: Pioneering work by Tony Wyss-Coray and colleagues, discussed by Topol, uses thousands of plasma proteins to calculate "organ age gaps," indicating how much older or younger an organ is compared to chronological age. These organ age gaps are strongly associated with future mortality and specific disease risks (e.g., accelerated heart aging with heart failure, brain aging with Alzheimer's disease). Notably, slow immune system aging and young brain age are strongly associated with improved survival.
• Biomarkers for Disease Prediction: Blood biomarkers like p-Tau217 are a "breakthrough" for accurately predicting Alzheimer's disease over 20 years in advance, showing dynamic responses to interventions like exercise. This offers a long "runway of opportunity" for early intervention through lifestyle changes or future drugs.

In Super Agers, Topol's holistic "Lifestyle+" paradigm emphasises that addressing these diverse, interconnected factors—from the quality of the air we breathe and the food we eat to the strength of our social bonds and our sleep patterns—is fundamental for extending healthspan and preventing age-related chronic diseases, offering a new blueprint for longevity.

Eric Topol, in his recent book Super Agers and through his Ground Truths newsletter, introduces the concept of "Lifestyle+" to highlight the profound, interconnected impact of various environmental and dietary factors on chronic disease and healthspan. This expanded view goes beyond traditional notions of healthy living (diet, exercise, sleep, and avoiding tobacco and excessive alcohol) to include critical environmental conditions and social determinants of health. He underscores that many healthy years can be added to our lives by addressing these factors, often without relying on expensive, high-tech medical interventions.

Here are the most significant environmental and dietary factors contributing to chronic disease and reduced healthspan, as discussed by Topol:

Environmental Factors

Environmental toxins represent a major, often underestimated, threat to healthspan.

• Air Pollution is identified as the leading contributor to the global disease burden.
  • Even short-term exposure to particulate matter (PM10 and PM2.5) is associated with increased all-cause, cardiovascular, and respiratory mortality, with no safe threshold identified for chronic effects of PM2.5 on cardiovascular health.
  • An estimated 20% of type 2 diabetes is linked to chronic exposure to fine particulate matter.
  • It also contributes to cognitive decline, reduced immune response, and increased blood pressure, primarily through mechanisms involving body-wide and brain inflammation, compromised immune function, and increased oxidative stress.
  • Outdoor pollution accounts for over 8 million premature deaths annually, with more than 80% potentially addressed by phasing out fossil fuels.
• Microplastics (MNPs) and Nanoplastics are ubiquitous and pose serious health hazards.
  • These industrially produced particles, carrying over ten thousand chemicals like bisphenols and phthalates, are found in our environment, food, air, oceans, and bottled water.
  • Crucially, MNPs have been detected in human arteries, brains, blood clots, liver, gut, lung, placentas, testicles, and other tissues.
  • A landmark study showed that the presence of MNPs in atherosclerotic plaque was associated with a 4.5-fold increased risk of all-cause mortality, heart attack, and stroke. This presence also correlated with marked inflammation in the arteries.
  • A new report highlights MNA accumulation in the brain, being 7-30 times greater than in the liver or kidneys, and significantly higher in individuals with dementia. Animal models show MNPs can cross the blood-brain barrier, activate the immune system, disrupt blood flow, and cause clots, leading to neurological abnormalities.
  • They are also linked to asthma, various cancers, cognitive decline, cardiometabolic disease, and infertility.
• Perfluorinated and Polyfluorinated Alkyl Substances (PFAS), or "forever chemicals," are prevalent and do not break down due to their strong chemical bonds.
  • High exposure to PFAS is linked to kidney and testicular cancer, obesity, increased blood pressure, high cholesterol, inflammatory bowel disease, and damage to the thyroid, liver, brain, and immune system.
  • Almost all Americans have measurable PFAS in their blood, primarily from sources including tap water, processed foods, clothing, and nonstick cookware.
• Secondhand Smoke, Radon, Pesticides, and Noise Pollution also contribute significantly to disease.
  • Secondhand smoke is linked to ischemic heart disease, stroke, type 2 diabetes, asthma, and breast cancer.
  • Moderate levels of indoor radon are associated with increased risk of non-smoking lung cancer and stroke.
  • Pesticides are linked to multiple cancers, type 2 diabetes, cognitive impairment, Parkinson's disease, and immune system issues.
  • Chronic noise pollution (>70 decibels), especially at night, is associated with increased stress hormones, body-wide inflammation, high blood pressure, heart disease, and type 2 diabetes.
• Ionizing radiation from medical imaging (CT scans, nuclear imaging) and exposure to certain metals (cadmium, tungsten, uranium, cobalt, copper, zinc) are also associated with increased cancer risk and cardiovascular disease, respectively.

Dietary Factors

Diet is considered paramount, with poor dietary patterns linked to 22% of all deaths globally, surpassing tobacco and other major health risks.

• Ultra-Processed Foods (UPFs) are described as "alien, industrially produced, unnatural substances; they're not even food".
  • These foods contain numerous additives and industrial ingredients, and their manufacturing processes (e.g., extrusion cooking) alter their texture to maximise digestibility and accelerate absorption, leading to spikes in blood glucose and insulin.
  • Randomised trials have shown that UPFs lead to overeating (an extra 500 calories per day) and weight gain.
  • They are associated with a markedly heightened risk of cardiovascular and metabolic diseases, including abnormal lipid levels, insulin resistance, systemic inflammation, metabolic syndrome (80% increased risk), type 2 diabetes (40% increased risk), hypertension (23% increased risk), obesity (55% increased risk), and cardiovascular death (66% increased risk).
  • Furthermore, UPFs are linked to a 62% increase in all-cause mortality with more than four servings per day, as well as higher risks of fatty liver disease, most types of cancer, sleep disorders, depression, and dementia. Even a 10% increase in UPF intake for older adults is associated with a 16% increased risk of cognitive impairment.
  • Topol emphasizes that UPFs must be restricted to the lowest level possible for healthy aging. The widespread influence of "Big Food" has hindered public health guidelines against UPFs in countries like the United States.
• Sugary Beverages, including fruit juices, are the biggest source of added sugar in the diet.
  • Their consumption is associated with a 24% increased all-cause mortality, as well as heightened cardiovascular and cancer-related mortality. Drinking more than two litres per week can increase the risk of atrial fibrillation more than threefold.
• Excessive Salt Intake is clearly linked to hypertension.
  • While moderate consumption is acceptable, intake exceeding 5 grams of sodium per day (the average American consumes about 3.5 grams) is associated with increased cardiovascular risk. High salt diets can also reduce blood flow to the brain, potentially increasing the risk of cognitive impairment.
• Harmful Carbohydrates: Both very low (<40%) and very high (>70%) daily caloric intake from carbohydrates are associated with increased all-cause mortality.
  • Low-quality, fast-digesting carbohydrates (like refined grains and potato products) cause high glycemic loads, raising insulin levels and predisposing to weight gain. A diet high in glycemic index is associated with a more than 25% increase in cardiovascular deaths. In contrast, good carbohydrates come from non-starchy vegetables, legumes, fruits, and whole grains.
• Red Meat and Processed Meats: These are at the "opposite ends of the spectrum" from plant-based diets in terms of health risks and environmental impact.
  • Processed meats (e.g., hot dogs, bacon, sausages) are classified as "carcinogenic to humans" by the World Health Organization. Unprocessed red meats (pork, beef) are "probably carcinogenic".
  • Regular consumption of ultra-processed red meat has been linked to a 14% higher risk of dementia.
  • Mechanistic studies show that red meat intake can reduce beneficial short-chain fatty acids (SCFAs), induce a "leaky" gut mucosa, and lead to the production of trimethylamine N-oxide (TMAO), strongly associated with increased risk of cardiovascular disease and potentially colon cancer. The gut microbiome of omnivores, especially those with high red meat intake, tends to feature inflammation-associated microbes.
  • Substituting processed red meat with healthier protein sources like nuts or legumes has been shown to reduce the risk of dementia and subjective cognitive decline.

Topol's "Lifestyle+" paradigm underscores that addressing these diverse, interconnected factors – from the microscopic pollution we breathe and ingest to the types of food we consume – is paramount for extending healthspan and preventing age-related chronic diseases.

Eric Topol, across his recent book Super Agers and his Ground Truths newsletter, frequently highlights the profound and often overlooked impact of diet on mortality and overall healthy aging. He underscores that diet is not merely about weight management but is a foundational element influencing health outcomes across virtually every organ system.

Indeed, a systematic assessment across 195 countries revealed that a poor diet is linked to 22% of all deaths globally, surpassing the mortality burden of tobacco, cancer, or hypertension. For healthy aging, Topol stresses that dietary choices can significantly alter one's health trajectory and lifespan. For instance, modelling studies suggest that transitioning from a typical Western diet to an optimal one at age twenty could increase lifespan by more than ten years. Similarly, adopting a healthy diet at age forty has been associated with a nine-year increase in life expectancy.

Let's delve into how specific dietary components influence mortality:

• Ultra-Processed Foods (UPFs) Topol describes UPFs as "alien, industrially produced, unnatural substances" that are "not even food". These foods, laden with additives and designed for rapid absorption, cause detrimental spikes in blood glucose and insulin. The evidence is deeply concerning:

  • Consumption of UPFs is linked to a markedly heightened risk of cardiovascular and metabolic diseases.
  • They are associated with an 80% elevated risk of metabolic syndrome, 40% higher risk of type 2 diabetes, 23% increased risk of hypertension, 55% risk of obesity, and 66% risk of cardiovascular death.
  • A significant 62% increase in all-cause mortality is linked to consuming more than four servings of UPF per day. This finding is robust, echoed by a comprehensive review of 45 studies following approximately 75,000 women and 40,000 men over three decades.
  • Beyond this, UPFs contribute to fatty liver disease, various cancers, sleep disorders, inflammatory bowel disease, depression, and dementia.
  • Topol unequivocally states that for healthy aging, UPFs "must be restricted in your diet to the lowest level possible".

• Sweeteners (Sugar and Artificial Sweeteners)

  • Added Sugar: Sugar-sweetened beverages are the largest source of added sugar. High consumption of these drinks, including fruit juices, has been associated with a 24% increased all-cause mortality in a large cohort, with similar findings for cardiovascular and cancer-related mortality in other studies.
  • Artificial Sweeteners: The picture here is "a bit more complicated" with conflicting reports. While some reviews find a lack of compelling evidence for risk, other large cohort studies have linked specific artificial sweeteners (aspartame, acesulfame potassium, sucralose) to increased cardiovascular and cerebrovascular disease risk. Overall, Topol suggests the data is "unfavourable, although it is not nearly as worrisome as high sugar consumption".

• Salt

  • The link between sodium intake and hypertension is clear, though the magnitude of effect is debated.
  • An extensive analysis indicated that moderate consumption (1-2 teaspoons or 2-5 grams of sodium) is not a problem, but cardiovascular risk becomes "obvious" at levels exceeding 5 grams of sodium per day.
  • High salt diets can reduce blood flow to the brain and potentially lead to cognitive impairment.
  • The use of potassium chloride salt substitutes has shown encouraging results, with a 40% reduction of hypertension in one trial and a systematic analysis supporting a reduction of all-cause and cardiovascular mortality.

• Macronutrients: Carbohydrates, Protein, and Fat

  • Carbohydrates: Excessive intake leads to "carbotoxicity". Moderation is key, as both very low (<40%) and very high (>70%) daily caloric intake from carbohydrates are associated with increased all-cause mortality. The type of carbohydrate is critical; dietary fiber (25-30 grams/day) is linked to a 15-30% reduced all-cause and cardiovascular mortality, type 2 diabetes, and colon cancer. In contrast, high glycemic index diets are associated with a greater than 25% increase in cardiovascular deaths.
  • Protein: The recommended daily allowance of protein (0.8 g/kg) may be underestimated for older individuals who need more to prevent muscle mass loss. However, excessively high protein diets (e.g., >1.5 g/kg) have been associated with increased atherosclerosis risk and pro-inflammatory gut microbiome metabolites. Topol recommends increasing protein intake up to 1.2 grams/kilogram of body weight but advises avoiding leucine-rich animal proteins.
  • Fat: The quality of fat, rather than just the quantity, is paramount. A shift to unsaturated mono- or polyunsaturated fats is associated with more favourable longevity data. The ketogenic diet, despite its popularity for weight loss, is linked to higher cholesterol, cardiovascular risk, and fatty liver disease.
  • Dairy: Contrary to older guidelines, consumption of two or more servings of dairy daily has been associated with 22% less cardiovascular disease and 17% less all-cause mortality, with whole-fat dairy showing a greater reduction. Yogurt and harder cheeses are particularly linked to better outcomes.

• Caffeine

  • Coffee consumption has been associated with up to a 30% reduced mortality, with maximal benefits seen around four cups per day. Studies indicate a 12% reduction in all-cause mortality and a 22% reduction in cardiovascular mortality, along with reduced risk of heart failure, several cancers, Parkinson's disease, and type 2 diabetes. While these are observational, Topol notes that the overall data suggests a lack of harm and potential benefits, even from decaffeinated coffee.

• Alcohol

  • Topol states that "both moderate and heavy drinking does one no good". The long-standing myth of red wine benefits has been refuted. Alcoholic beverages are classified as carcinogenic, with strong links to oral cavity and esophageal cancers. While some studies suggest a "J-curve" effect, with a potential small benefit for very light intake (e.g., two drinks per week), risks increase quickly beyond this level. A causal link between alcohol consumption and cardiovascular disease has been supported by genetic studies.

• Red Meat and Plant-Based Diets

  • These represent "opposite ends of the spectrum for reduced versus increased risk of mortality".
  • Processed meats (hot dogs, bacon) are considered carcinogenic by the WHO and are linked to the highest risks. Unprocessed red meats are "probably carcinogenic".
  • Multiple prospective studies have shown an association between red meat ingestion and an increased risk of all-cause mortality, with processed meats posing a higher risk.
  • New mechanistic insights suggest red meat intake reduces beneficial short-chain fatty acids (SCFAs) in the gut, promotes a "leaky mucosa," and leads to the production of trimethylamine N-oxide (TMAO), which is strongly associated with increased cardiovascular disease and potentially colon cancer.
  • Conversely, plant-based diets are "plainly healthier". They are linked to a 23% lowered risk of type 2 diabetes, and meta-analyses show substantial protection from all-cause mortality, cardiovascular deaths, and type 2 diabetes when processed meat is substituted with plant-based foods. Plant protein intake alone has been associated with an 11% reduced risk of total and cardiovascular-related mortality. A recent study found that the increased risk of dementia and cognitive decline associated with processed red meat could be mitigated by replacing it with nuts or legumes.

• "Good Foods" and Healthy Eating Patterns (e.g., Mediterranean Diet)

  • Healthy eating patterns include fruits, vegetables, legumes, whole grains, nuts, seeds, healthy fats (like olive oil and avocados), and fatty fish rich in omega-3s.
  • Olive oil consumption has been tied to about a 20% lower all-cause mortality, along with reductions in cardiovascular-, cancer-, and neurodegenerative-related deaths.
  • The Mediterranean diet, a composite of these "good foods," is strongly supported by randomized trials and observational studies. It is associated with a reduction of death from any cause—including cardiovascular diseases, cancer, and neurodegenerative diseases. In one significant trial, participants at high risk for heart disease experienced a 30% lower risk of cardiovascular death, heart attack, or stroke when adhering to a Mediterranean diet.
  • Such diets also promote a healthier gut microbiome, reducing inflammation and improving cognitive function.

• Caloric Restriction and Time-Restricted Eating

  • Historical data from World War I in Denmark showed dietary restriction associated with a 34% reduction in mortality.
  • Less stringent alternatives like time-restricted eating (e.g., 16:8 schedule) and intermittent fasting have shown benefits for insulin signalling and other pathways, similar to more extreme caloric restriction.
  • Topol's practical advice, especially given the difficulties of long-term adherence to strict caloric restriction, is to eat an early dinner (at least three to four hours before bedtime) and avoid caloric intake until breakfast.

• Supplements

  • Despite their popularity and extensive marketing, Topol maintains there is "little or no hard evidence for the benefit of taking any vitamins or supplements," particularly in individuals following a healthy diet. Many large trials have failed to show benefit for vitamin D, omega-3 fatty acids, and multivitamins for cardiovascular disease, cancer, or cognitive preservation. Some supplements, like calcium plus vitamin D, have even been associated with increased risks of stroke and cardiovascular mortality.

The Role of Emerging Technologies and Personalized Nutrition Topol emphasizes that the "one-size-fits-all" approach to diet is naive, given each person's unique biology, including their genome, metabolism, and gut microbiome. Advances in high-throughput proteomics, which can measure thousands of plasma proteins, combined with AI, are beginning to provide unprecedented insights into how diet impacts organ-specific aging and disease risk. Studies are exploring how an individual's gut microbiome dictates their response to food, as measured by glucose and triglyceride spikes. While still in early stages, AI-driven personalized nutrition has shown promise in improving glucose regulation in prediabetic individuals. Topol envisions a future where such data could guide individuals towards optimal dietary choices, potentially preventing or delaying age-related diseases.

Ultimately, as Topol concludes in his work, our understanding of diet's role in health and mortality has been "refined and our knowledge has grown tremendously". Despite many studies being observational, their consistent patterns, often with dose-response relationships, collectively form a compelling body of evidence highlighting diet as a cornerstone of "lifestyle+" for extending healthspan and reducing mortality.