**Official Longevity Thread** (1 Viewer)

[brun]

If this has been discussed and I’ve missed it, I apologize.

@Terminalxylem I’m curious if you think there might be anything to some of the claims and studies about earthing/grounding.

Sounds really pseudoscience-y to me, though I haven’t researched it at all. It would be really hard to prove it does anything, due to confounders.

Here is the first review I pulled up, FWIW.

I'm curious if people working in electronics, who sometimes use ground straps all day to protect sensitive devices, are healthier than average.

 

[MTskibum]

Hopefully 2-3 independent researchers pick up below claim. The problem is that double blind studies involving psilocybin are impossible is the conclusion that other researchers came to when trying to setup a double blind study involving psilocybin. They noted that near 100% of the time patients could tell when they got the placebo verse when they got the drug.

Psilocybin, the main psychoactive ingredient in magic mushrooms, extends the lifespan of human cells, a lab study suggests. Researchers also found that the psychedelic compound slows certain hallmarks of aging in older mice while improving their fur quality.

The findings, published July 8 in the journal npj Aging, provide the first experimental evidence of psilocybin's potential anti-aging properties.

'I was floored by the data': Psilocybin shows anti-aging properties in early study

The psychedelic psilocybin, found in magic mushrooms, slows certain hallmarks of aging in human cells and older mice, a lab study suggests.

www.livescience.com

 

[Softballguy]

Not sure if this is helpful, but Google’s AI-powered study tool, NotebookLM, provides access to expert-curated notebooks covering a wide variety of topics, including Eric Topol's NotebookLM on "Secrets of the Super Agers."

I haven't spent a ton of time looking at NotebookLM notebooks, but it looks promising.

Get health and longevity advice by drawing on the expertise of bestselling author Eric Topol, professor at the Scripps Research Institute and one of the most cited researchers in all of medicine. Ask lifestyle questions about diet, sleep or exercise and get detailed, science-backed recommendations, based on Topol's latest book, Super Agers and his popular Substack, Ground Truths. Listen to Audio Overviews explaining the importance of healthspan over lifespan and the new possibilities of an AI diet, or explore a mind map of all the longevity-related topics covered in the notebook.

 

[Terminalxylem]

Diet: Topol highlights that diet is profoundly important, noting a systematic assessment that linked poor diet to 22% of all deaths globally, exceeding tobacco or cancer.

• Ultra-Processed Foods (UPFs): These industrially produced substances are described as "alien" and "not even food". Their damage comes from chemical additives and physical processing that accelerate digestion, leading to spikes in blood glucose and insulin. A randomized trial by Kevin Hall and colleagues at NIH demonstrated that consuming UPFs led to an extra 500 calories eaten per day and significant weight gain. Topol details how UPFs are associated with a markedly heightened risk of numerous conditions, including cardiovascular and metabolic diseases, insulin resistance, inflammation, type 2 diabetes, obesity, cognitive impairment, cancer, and even a 62% increased risk of all-cause mortality with over four servings daily. He, like Chris van Tulleken, a British physician-scientist and author of Ultra-Processed People, points to dramatic internal changes, such as hormonal shifts and body-wide inflammation, observed in individuals on high-UPF diets. Topol strongly advises minimizing UPF intake by reading labels, avoiding additives and artificial sugars, and primarily shopping the perimeter of grocery stores where fresh foods are found. He critically notes the "supersized chokehold influence" of Big Food on U.S. regulatory bodies like the FDA, which he suggests has led to a lack of awareness or action regarding UPF dangers, likening them to cigarettes in terms of suppressed public awareness.
• Sweeteners: Excessive sugar, particularly from sugar-sweetened beverages, is clearly detrimental, linked to increased mortality and cardiovascular issues. Artificial sweeteners, while less worrisome than sugar, have conflicting data, with some studies suggesting associations with cardiovascular disease and changes in the gut microbiome.
• Salt: The link between sodium intake and hypertension is clear, though its effect size varies. High intake (over 5 grams/day) is associated with increased cardiovascular risk and even cognitive impairment. Topol suggests limiting added salt and considering potassium chloride substitutes.
• Macronutrients – It's About Quality: Topol stresses that the subtype of carbohydrates, protein, and fat is crucial.
  • Carbohydrates: "Carbotoxicity" refers to risks from excessive carbs, but good quality carbs like dietary fiber (25-30 grams/day from non-starchy vegetables, legumes, fruits, whole grains) are highly beneficial, linked to reduced mortality, type 2 diabetes, and colon cancer. Low-quality refined grains, however, are associated with weight gain and increased cardiovascular deaths.
  • Protein: Current dietary recommendations for protein may be too low for older adults to prevent age-related muscle loss (sarcopenia). While higher protein intake may be needed, Topol cautions against excessive leucine-rich animal proteins, which have been linked to atherosclerosis and pro-inflammatory metabolites.
  • Fats: The quality of fat matters more than its total amount. Unsaturated fats, especially plant-based ones like olive oil and avocados, are associated with better longevity and reduced cardiovascular and type 2 diabetes risk. The ketogenic diet, despite its popularity, is linked to higher cholesterol, cardiovascular risk, and fatty liver disease. Dairy products, once discouraged for their fat content, are now, counter-intuitively, linked to reduced cardiovascular disease and type 2 diabetes, particularly unsweetened yogurt and hard cheeses.
• Red Meat and Plant-Based Diets: Processed meats are classified as carcinogenic, and unprocessed red meat as "probably carcinogenic," both associated with increased mortality. Topol highlights that plant-based foods are "plainly healthier," consistently linked to reduced risks of type 2 diabetes, all-cause mortality, cardiovascular disease, and cancer. New research discussed by Topol underscores red meat's negative impact on the gut microbiome (promoting inflammation) and its association with dementia and cognitive decline, noting that these risks can be mitigated by substituting plant-based proteins.
• The Mediterranean Diet: Topol underscores the Mediterranean diet as a "whole package" of "good food" (fruits, vegetables, legumes, whole grains, nuts, seeds, healthy fats, fatty fish) that is robustly supported by randomized trials. It has shown significant benefits for reducing all-cause mortality, cardiovascular diseases, cancer, and neurodegenerative diseases, and even positively modulates the gut microbiome to reduce frailty and inflammation in older adults.
• Caloric Restriction and Time-Restricted Eating: While promising in some experimental models for longevity, strict caloric restriction is difficult to maintain and can lead to bone and muscle loss. Time-restricted eating (e.g., 16:8) and intermittent fasting are less extreme but have mixed results in human trials. Topol's practical advice is to eat an early dinner, at least 3-4 hours before bed, and avoid caloric intake until breakfast, aligning with circadian rhythms.
• Supplements: Topol takes a skeptical stance on most supplements, stating there's "little or no hard evidence for the benefit of taking any vitamins or supplements, especially in those who are following a healthy diet". He notes some promising, but unproven, "longevity vitamins" like taurine and choline, but advises taking such claims "with a grain of salt" until randomized trials provide definitive evidence.

Environmental Toxins: An Unacknowledged Burden​

Toxins pose "significant risks" and are often inadequately recognized or addressed.

• Air Pollution: Identified as the leading contributor to global disease burden, even short-term exposure is linked to increased mortality, and there's no safe threshold for chronic exposure. It's tied to type 2 diabetes, cognitive decline, inflammation, and increased lung cancer risk.
• Other Widespread Toxins:
  • Secondhand smoke and radon are recognized indoor health hazards.
  • Pesticides are associated with various cancers, type 2 diabetes, and neurological conditions.
  • Noise pollution, particularly at night, is linked to increased stress hormones, inflammation, and cardiometabolic issues.
  • Microplastics (MNPs) and Nanoplastics: Topol expresses deep concern over these pervasive substances. They carry thousands of chemicals and are now ubiquitous, found in our air, water, food, and almost every human organ, including the brain, arteries, blood clots, placenta, and testes. A "landmark prospective study" highlighted by Topol revealed MNPs in the carotid artery plaques of 58% of patients, correlating with marked inflammation and a 4.5-fold heightened risk of heart attack, stroke, or death. Disturbingly, new research shows MNPs accumulate in the brain, with 7-30 times higher concentrations than in other organs, and are significantly elevated in the brains of people with dementia. Mouse models further suggest MNPs can cross the blood-brain barrier, activating immune responses, causing blood flow stagnation, and leading to clots and neurological abnormalities. Topol stresses that despite the "overwhelming accumulation of evidence for their toxicity," little is being done, and calls for urgent action to reduce plastic production and reliance on single-use items.
  • PFAS ("Forever Chemicals"): These human-made chemicals persist indefinitely and are linked to various cancers, obesity, high blood pressure, and damage to multiple organ systems, with most Americans having measurable levels in their blood. Regulation is minimal.
  • Ionizing radiation from medical imaging (CT scans) and metals are also cited as contributors to health hazards.

Topol concludes environmental factors likely contribute to the "marked rise of various cancers in younger adults in recent years".

 

[Terminalxylem]

Exercise: The "Miracle Breakthrough"​

Topol champions regular exercise as the "single most effective medical intervention that we know, with profound, diverse benefits across all organ systems.

• Comprehensive Benefits: Exercise leads to favorable adaptations in the cardiovascular system, brain, pancreas, muscles, gut, liver, adipose tissue, and immune system. It boosts insulin sensitivity, protects against atherosclerosis, reduces inflammation, and enhances mitochondrial function.
• MoTrPAC Initiative: Topol highlights the NIH's Molecular Transducers of Physical Activity Consortium (MoTrPAC), which has provided multiomic data validating the protective effects of physical training across multiple organs. Discussions with MoTrPAC leader Euan Ashley reveal that regular exercise "literally every tissue is changed dramatically," with findings supporting the concept of hormesis—that the body learns to deal with stress through recurrent exercise. Ashley emphasizes that the "multisystem, multi-tissue, multidimensional response to exercise" means an "exercise pill" is unlikely. Topol also notes the "sex-specific findings" that underscore how exercise affects males and females differently, particularly in adipose tissue.
• Quantified Impact: As Euan Ashley relays, "one minute of exercise bought you five minutes of extra life," and "seven or eight minutes" for high-intensity exercise. Brisk walking for 450 minutes per week is associated with living 4.5 years longer. A systematic review linked increased physical activity to a 31% reduction in all-cause mortality.
• Types and Intensity: Topol corrects his own past focus on only aerobic exercise, stressing the equal importance of strength, resistance, and balance training as we age. While moderate activity (brisk walking, gardening) offers significant benefits, higher intensity exercise can yield additional gains. He notes the often-cited 10,000 steps/day goal is unvalidated, with studies showing benefits starting much lower (e.g., 2,500-2,700 steps/day) and plateauing around 7,500-8,800 steps/day for mortality reduction. Resistance training, even for 60 minutes/week, is linked to a 25% reduction in all-cause mortality, along with benefits for muscle mass, bone density, and mental well-being. Grip strength and balance are highlighted as crucial prognostic metrics for healthy aging.
• Mental and Cognitive Health: Exercise "seems to do wonders" for depression, anxiety, and stress, potentially outperforming some medications. It's also linked to reduced dementia risk and improved cognitive function, partly through increased brain neurogenesis and anti-inflammatory effects. Notably, exercise has been shown to lower levels of p-Tau217, a crucial biomarker for Alzheimer's disease.
• "Never Too Late": Topol cites the inspirational case of Richard Morgan, a 93-year-old who began regular exercise in his seventies and achieved extraordinary fitness, demonstrating that exercise can counter and potentially even reverse age effects.
• Sitting is Detrimental: Prolonged sitting is independently linked to higher all-cause and cardiovascular mortality, though physical activity can mitigate some of these effects.

Sleep: The Brain's "Dishwasher"​

Topol describes sleep as a "non-negotiable biological state" fundamental to health and restoration.

• Glymphatic System and Waste Clearance: Recent scientific advancements have revealed the brain's unique "glymphatic system," a plumbing network that clears metabolic waste products, like beta-amyloid (a precursor to Alzheimer's disease), primarily during non-rapid eye movement (NREM) sleep. Topol quotes pioneering researcher Maiken Nedergaard: "Sleep is like turning on the dishwasher before you go to bed and waking up with a clean brain". Even a single night of sleep deprivation can lead to beta-amyloid accumulation.
• Brain Aging: As we age, glymphatic efficiency declines, leading to waste accumulation and contributing to neurodegenerative diseases. There's a vicious cycle where decreased sleep leads to more toxic proteins, which in turn disrupt sleep.
• Optimal Duration and Health Outcomes: Topol highlights that about seven hours of sleep is optimal. Both insufficient sleep (less than 6 hours) and excessive sleep (more than 8 hours) are consistently linked to cognitive and mental health decline, unfavorable brain structure changes, and heightened all-cause, cardiovascular, and cancer mortality.
• Sleep Epidemic: A significant portion of Americans (35-40%) regularly sleep less than seven hours.
• Sleep Aids: Topol expresses strong concern about common sleep medications like Ambien (zolpidem), noting that it suppresses glymphatic flow and has been associated with increased Alzheimer's and dementia risk. He states that "none of the commonly used sleep medications or supplements have been shown to improve waste clearance... or promote deep slow-wave sleep without important side effects".
• Promoting Healthy Sleep: Instead, Topol advises focusing on behavioral and lifestyle factors: maintaining a regular sleep schedule, consistent exercise and meal times (with early dinner), a cool, dark, quiet bedroom, avoidance of blue light before bed, and addressing conditions like sleep apnea.

Social Isolation and Socioeconomic Status​

Topol stresses the mounting evidence that loneliness and social isolation are critical public health concerns, linking them to significantly increased all-cause, cardiovascular, and cancer-related mortality. He notes the strong impact of socioeconomic status (SES) as an independent risk factor for premature mortality, as significant as smoking or obesity. Lower SES is disproportionately associated with poorer diet quality, inadequate sleep, higher air pollution exposure, and less physical activity. Topol strongly advocates for dedicated efforts to combat these inequities to ensure that health span improvements are not restricted to certain socioeconomic groups.

The Future of Measuring Health: Precision and Prevention​

Topol is enthusiastic about emerging technologies that will revolutionize how we measure and predict health, moving towards personalized and proactive care.

• p-Tau217: A Breakthrough for Alzheimer's: Topol describes the plasma p-Tau217 biomarker as "one of the most exciting advances in neurology for decades". It offers highly accurate prediction of Alzheimer's disease (AD) by tracking brain neuropathology, appearing more than 20 years before symptom onset. This early detection provides a long "runway of opportunity" for intervention. Crucially, p-Tau217 levels are dynamic and can be lowered by interventions like exercise. While the Alzheimer's Association has advocated for broad screening, Topol argues against routine use in cognitively intact individuals or labeling elevated levels as "Stage 1 Alzheimer's," instead seeing its utility as part of a comprehensive risk assessment for targeted prevention. He envisions a future where p-Tau217 could guide AD prevention akin to how LDL cholesterol guides statin use for heart disease.
• Proteomic Organ Clocks: Pioneering work by Tony Wyss-Coray and others allows for the measurement of thousands of plasma proteins to identify "organ age gaps"—differences between a person's chronological age and the biological age of their individual organs. Topol highlights that about 1 in 5 individuals are "extreme agers" for at least one organ, and these organ-specific age gaps are linked to increased mortality and specific disease risks (e.g., accelerated heart aging linked to heart failure, brain aging to Alzheimer's). These clocks are sensitive to lifestyle factors, offering a way to track the impact of interventions like diet, exercise, and alcohol on individual organs. Topol sees this as a more realistic objective than slowing body-wide aging.
• High-Throughput Proteomics and AI: The ability to measure thousands of plasma proteins, coupled with AI analytics, represents a "quiet revolution". This rich data, integrated with other information like electronic health records and genomics, provides new insights into disease underpinnings, aging, and individualized health forecasting. Proteomic studies have shown that aging is not a linear process, with protein expression peaking at specific ages. This approach can also establish causal relationships between proteins and diseases, and identify modifiable risk factors. Importantly, Topol notes that proteomic signatures can provide a more objective assessment of adherence to dietary patterns than traditional self-reported food diaries.
• The AI Diet: Topol underscores the "naive" notion of a one-size-fits-all diet, given each person's biological uniqueness. Personalized nutrition, leveraging AI to integrate vast datasets (genome, microbiome, metabolism, lifestyle), is the future. He points to seminal work demonstrating the gut microbiome as a key determinant of individual glucose responses to food, measurable by continuous glucose monitors (CGMs). While CGMs are increasingly available, the long-term health outcomes of precisely avoiding glucose spikes are still being studied.

Topol concludes that while these high-tech advancements are exciting and hold "considerable promise to revamp our assessment of health and disease," our ability to prevent or substantially delay age-related diseases will always depend significantly on our attention to these "lifestyle+" factors.

 

[Terminalxylem]

^AI-generated summary of Topol’s book.

Nothing earth-shattering, imo. Nice to see him call out red meat, ketogenic diets, and supplements, while emphasizing uncertainty with time-restricted feeding/fasting. Seems like popular guys like Attia, Huberman, etc. are acting contrary to some of his recs.

Some doctors, like Peter Attia, have advocated for intake of one gram per body weight in pounds (not per kg), which has not been substanti-ated by evidence. Indeed, a study of high-protein diets in people and mice warned of the danger of promoting atherosclerosis through an increase in plasma leucine, an essential amino acid building block of proteins, and im-paired cellular waste disposal (autophagy). The gut microbiome of people who consume a high-protein diet (more than 1.5 g/kg) has been shown to produce pro-inflammatory metabolites. While increasing your diet up to 1.2 gram/kilograms of protein is reasonable, it's the leucine-rich animal proteins that should be avoided. High-protein diets are intended to reduce the risk of sarcopenia—age-related loss of muscle mass and strength—which has been unequivocally demonstrated (in many studies, such as quantify-ing handgrip) is a well-established risk factor for reduced health span. We don't know that increasing protein in the diet with age titrates or negates that risk, which would require a randomized trial with multiyear follow-up that will likely never get done. (That's because randomized trials of diets are extremely hard to do at scale; also, it's difficult to rely on participants' long-term adherence and difficult to obtain financial support.) Further-more, there's no information on food labels about the specific amino acids (nine of the twenty) in our diet that we require because we can't synthesize them—such as leucine, lysine, and methionine. Note that the recommen-dations above break down fats but not proteins. The hard truth is that we could be doing so much more to upgrade our knowledge of dietary protein intake that's not being done.

Tl;dr Eat a minimally processed, plant-based diet, exercise a lot, sleep 7ish hours a day, avoid environmental toxins, and maintain social connections to optimize life- and healthspan.

 

[Joe Bryant]

Tl;dr Eat a minimally processed, plant-based diet, exercise a lot, sleep 7ish hours a day, avoid environmental toxins, and maintain social connections to optimize life- and healthspan.

Outside of the plant based, I think that's exactly what guys like Huberman and Attia are promoting, aren't they? I'm not super familiar with exactly what each promote but from the understanding I have, they're exactly in line there except for Huberman on plant based.

 

[Terminalxylem]

Tl;dr Eat a minimally processed, plant-based diet, exercise a lot, sleep 7ish hours a day, avoid environmental toxins, and maintain social connections to optimize life- and healthspan.

Outside of the plant based, I think that's exactly what guys like Huberman and Attia are promoting, aren't they? I'm not super familiar with exactly what each promote but from the understanding I have, they're exactly in line there except for Huberman on plant based.

Arguably, the single most important component of diet, outside of avoiding ultraprocessed foods, is that it should be plant based.

Attia poo-poos the whole field of nutrition, citing legitimate concerns about confounders and outside influence. But he’s throwing the baby out with the bathwater, imo, as there’s enough restrospective and population data to show clear trends.

Moreover, he advocates very high protein intake throughout life, which conflicts with animal studies on protein restriction and longevity, and one large human study showing increased mortality amongst middle aged adults with high (animal) protein intake.

Attia eats and promotes venison jerky as a staple of his diet. Huberman is a self-professed “omnivore”. They’re both pretty vague about how much plant vs. animal stuff they consume. But it’s clear they prioritize protein and avoiding sarcopenia, while relegating plants to a supporting role.

Maintaining muscle mass is important for functionality, of course, but consistent exercise (daily cardiovascular, with a couple resistance training sessions weekly) and more modest (1-1.6 gram/kg bodyweight/day vs. 1 g/pound) protein intake, predominantly from plant sources, can achieve that goal.

Essentially, you’re balancing your risk from dying from a fall (which increases with age) against dying from heart disease and cancer (much more common). I think Topol’s approach is more congruent with what we currently know about healthy aging, while the gym-bros are putting too much emphasis on muscle.

 

[Terminalxylem]

But yes, Joe, they advocate regular exercise, sleep, and social connections. I assume they agree to minimize environmental toxins as well.

I just have a hard time with their conspicuous avoidance of certain nutrition topics, while simultaneously advocating foods/supplements that aren’t clearly associated with health, at best, and may actually be harmful. With otherwise thoughtful insights into the science, it makes me wonder about secondary gain.

Specifically, I think they don’t want to alienate their audience, or sponsors (Huberman).

Low carbohydrate diets have caused people to liberalize animal protein intake, which is American’s tendency anyway, and protein is being gratuitously added to everything nowadays. At the same time, “plant-based” is erroneously seen as shorthand for vegan (by some), which carries negative stereotypes of weakness, sanctimoniousness, and even political affiliation. Middle age dudes and gym aficionados don’t want to hear it.