Importance of Sleep

Eric Topol, in his new book Super Agers and through his Ground Truths newsletter, consistently champions sleep as an absolutely essential component of a healthy "lifestyle+", equating its necessity to that of air, food, and water. He underscores how restful, high-quality sleep is crucial for extending healthspan and maintaining well-being across nearly every physiological system.

Here's a detailed look at the profound importance of sleep, drawing from the sources:

The Brain's "Plumbing System": Glymphatic Clearance

• Discovery and Function: A major breakthrough in understanding sleep's vital role came in 2012 with Maiken Nedergaard's discovery of the brain's glymphatic pathway. This system, analogous to the body's lymphatic system but without lymph nodes, is a network of fluid-filled channels alongside blood vessels that drains metabolic waste from the brain and facilitates cerebrospinal fluid movement.
• Waste Clearance During Sleep: The glymphatic system is primarily active during non-rapid eye movement (NREM) sleep, particularly deep, slow-wave sleep (stage N3). During this phase, large waves of cerebrospinal fluid flow act as a "pump," driven by norepinephrine levels and blood-brain volume oscillations, to clear out toxic proteins and metabolic waste.
• "Neurons that fire together, shower together": Recent Nature publications highlighted that synchronized neuronal activity is critical for activating glymphatic waste clearance, indicating that neurons act as "master organizers" for this crucial "brainwashing" process.
• Clearing Beta-Amyloid: The efficient clearance of toxic proteins, such as beta-amyloid, is fundamental to brain health. A single night of sleep deprivation can lead to a substantial increase in beta-amyloid accumulation in brain regions linked to Alzheimer's disease, and chronically poor sleep is prospectively linked to the risk and progression of this neurodegenerative condition.

Broad Health Outcomes Linked to Sleep

• Reduced Mortality: The relationship between sleep and health outcomes is profound, impacting all-cause mortality, cardiovascular mortality, and cancer mortality. Studies from the UK Biobank, tracking nearly 99,000 participants with sleep trackers, showed clear correlations between sleep regularity and reduced mortality risks.
• Cardiovascular and Metabolic Health: Sleep deprivation and poor sleep regularity are associated with a significant rise in heart attacks (e.g., following daylight savings time) and increased risk of total cardiovascular disease. It also negatively impacts metabolic function, increasing the risk of type 2 diabetes and metabolic syndrome, partly through deleterious pro-inflammatory changes at the molecular level in adipose tissue and muscle.
• Cognitive Function and Mental Health: Optimal sleep duration is crucial for cognition and mental health. Poor sleep is linked to an increased risk of dementia, with studies showing a 30% increased risk for individuals aged 50-60 sleeping six hours or less. Exercise, as discussed by Topol and Euan Ashley, indirectly supports brain health by promoting better sleep, which is the primary driver for clearing metabolic waste from the brain.
• Immune System: Sleep plays a vital role in immune system function.

Optimal Sleep Duration: The "Sweet Spot"

• Seven Hours is Key: Research, including data from nearly 500,000 UK Biobank participants, indicates that about seven hours is the optimal duration of sleep.
• Risks of Too Little or Too Much: Both insufficient sleep (less than seven hours) and excessive sleep (more than eight hours) are associated with adverse outcomes. Each hour below the 7-8 hour threshold is linked to a 6% higher risk of total cardiovascular disease, while each hour above it is associated with a 12% higher risk. Long sleep duration (more than eight hours) is consistently associated with cognitive and mental health decline and a heightened all-cause mortality risk of approximately 30%.

Sleep Challenges in Aging Adults

• Decline in Deep Sleep: Older adults face unique sleep challenges, notably a significant reduction in precious NREM deep, slow-wave sleep. By the late forties, deep sleep is over 60% lower than in teenagers, and by age seventy, it can be down 80-90%.
• Fragmented Sleep and Circadian Regression: They also experience more fragmented sleep (reduced sleep efficiency) and a regression of circadian timing, leading to earlier bedtimes and awakenings. This is critical because disrupted meal timing also desynchronises circadian clocks, inducing glucose intolerance.
• Vicious Cycle: The aging brain naturally accumulates metabolic waste and experiences diminished glymphatic and meningeal lymphatic drainage, which can be exacerbated by sleep disruption, creating a vicious cycle where decreased sleep leads to more toxic proteins, which then interfere with sleep.

The Perils of Sleep Medications

• Ambien's Adverse Effect: Ironically, commonly used sleep aids can be detrimental. Ambien (zolpidem) has been shown to suppress norepinephrine effects and reduce glymphatic flow, essentially "backfiring" on the brain's waste disposal mechanism.
• Broader Concerns: Benzodiazepine-like sleep medications have been associated with a heightened risk of Alzheimer's disease and dementia, potentially through their impairment of "brainwashing" processes. Topol notes that none of the commonly used sleep medications or supplements have been proven to improve waste clearance or promote deep sleep without significant side effects.

Promoting Healthy Sleep: Lifestyle Interventions

Given the lack of effective and safe pharmacological interventions for sleep quality, Topol emphasises behavioral and lifestyle factors:

• Regularity: Maintaining consistent bedtime and awakening schedules, even on weekends, is crucial.
• Exercise: Regular physical activity, while not explicitly mentioned as a direct driver of glymphatic flow (that's sleep's role), is a key part of a healthy lifestyle that promotes better sleep quality.
• Dietary Habits: Avoiding late-night eating, particularly within a few hours of bedtime, aligns with time-restricted eating principles and supports healthy sleep.
• Environment: A cool, fully dark, and quiet bedroom, along with avoiding blue light from electronic devices, helps regulate circadian rhythm and melatonin production.
• Addressing Sleep Apnea: This common sleep disruption significantly increases the risk of cardiovascular and metabolic diseases and should be diagnosed and managed in symptomatic individuals.
• Relaxation Techniques: Cognitive behavioral therapy, including digital versions via smartphone apps, is a first-line treatment for improving sleep quality and insomnia symptoms.

Topol highlights that while much has been known about diet and exercise for millennia, our knowledge about sleep and its impact on healthy aging has grown tremendously. Investing in better sleep through these lifestyle adjustments is a fundamental step towards a longer, healthier life, consistent with the overarching message of Super Agers.

The glymphatic system is a crucial, recently discovered "plumbing system" of the brain, analogous to the body's lymphatic system but operating without lymph nodes. Eric Topol, in his Ground Truths newsletter and Super Agers book, frequently highlights this system as fundamental to brain health and healthy aging, particularly in its role of waste clearance.

Here's a breakdown of what the glymphatic system is and how it functions:

• Discovery: The glymphatic pathway was discovered in 2012 by Maiken Nedergaard and her colleagues at the University of Rochester.
• Structure and Function: It consists of a network of fluid-filled channels, specifically involving aquaporin-4 (AQP4) expressed on astrocytes, that run alongside blood vessels (paravascular spaces). Its primary function is to drain metabolic waste from the brain and facilitate the movement of cerebrospinal fluid (CSF).
• Mechanism of Waste Clearance:
  • Cerebrospinal fluid (CSF) flows through this network, flushing out interstitial solutes and metabolic waste.
  • This process is primarily active during non-rapid eye movement (NREM) sleep, especially during deep, slow-wave sleep (stage N3).
  • During NREM sleep, oscillations in blood-brain volume, mediated by norepinephrine levels, act as a "pump" to drive glymphatic flow.
  • Recent Nature publications in early 2024 demonstrated that synchronised neuronal activity is crucial for activating glymphatic waste clearance, leading to the phrase: "neurons that fire together, shower together". Blocking neuronal firing prevents waste clearance.
  • Brain macrophages, specifically parenchymal border macrophages (PBMs), also play an important role in this flow pattern.
  • Waste material accumulating around arteries is cleared alongside veins to lymphatics outside the brain, including meningeal lymphatic vessels and neck lymph nodes.
• Importance for Brain Health: The efficient clearance of toxic proteins, such as beta-amyloid, is critical. Accumulation of beta-amyloid is a known precursor to Alzheimer's disease. A single night of sleep deprivation can lead to a substantial increase in beta-amyloid in brain regions linked to Alzheimer's. Chronically poor sleep is prospectively linked to the risk and progression of Alzheimer's disease. The glymphatic system is essentially "turning on the dishwasher before you go to bed and waking up with a clean brain," as Maiken Nedergaard describes it.
• Impact of Aging: As individuals age, the efficiency of glymphatic and vascular dynamics decline, and sleep becomes more disrupted, with less NREM deep, slow-wave sleep and less synchronised neural activity. This contributes to the accumulation of metabolic waste and toxic proteins in the brain, creating a vicious cycle where decreased sleep leads to more toxic proteins, which then interfere with sleep. The exit route of meningeal lymphatics also diminishes in the aged brain, accompanied by chronic inflammation.
• Adverse Effects of Sleep Aids: Ironically, some common sleep medications can hinder this vital process. For example, Ambien (zolpidem) has been shown to suppress norepinephrine effects and reduce glymphatic flow, effectively "backfiring" on brain waste disposal. Benzodiazepine-like sleep medications have been associated with a heightened risk of Alzheimer's and dementia, possibly through impairment of these "brainwashing" mechanisms.

Topol emphasises that while much of this knowledge was initially accumulated from rodent models, the first demonstrations of glymphatics in humans were reported in late 2024. Understanding and promoting healthy sleep is therefore paramount for maintaining effective glymphatic function and safeguarding brain health against age-related neurodegenerative diseases.

Eric Topol, in his new book Super Agers and through his Ground Truths newsletter, frequently underscores sleep as a non-negotiable biological state essential for human life and healthy ageing, akin to the fundamental needs for air, food, and water. Improving sleep is crucial, particularly because of its profound impact on brain health and overall longevity.

The Critical Role of Sleep and Consequences of Poor Sleep

Topol highlights the groundbreaking discovery of the brain's glymphatic pathway, a "plumbing system" that clears metabolic waste products, including toxic proteins like beta-amyloid, primarily during non-rapid eye movement (NREM) sleep. This process is vital for preventing what Maiken Nedergaard, the discoverer, likens to "dirty brains that age faster". Neuronal synchronisation, driven by norepinephrine levels and blood-brain volume oscillations, acts as a "pump" for this waste clearance.

Insufficient or poor sleep has widespread adverse effects:

• Increased risk of dementia: Even one night of sleep deprivation can lead to a substantial increase in beta-amyloid accumulation in Alzheimer's-related brain regions. Chronically poor sleep (six hours or less at ages 50-60) is associated with a 30% increased risk of dementia.
• Cardiovascular and metabolic issues: Poor sleep is linked to increased all-cause, cardiovascular, and cancer mortality. It can cause pro-inflammatory changes in adipose tissue and muscle, increase the risk of heart attacks, and affect metabolic function and obesity.
• Cognitive and mental health decline: Both insufficient and excessive sleep are associated with cognitive and mental health decline and unfavourable brain structure changes.

Optimal Sleep Duration and Ageing Challenges

Research, particularly from the UK Biobank, indicates that approximately seven hours of sleep is optimal. Both sleeping less than seven hours and more than eight hours are associated with adverse outcomes and heightened mortality risk.

As people age, sleep quality often deteriorates, presenting a threefold problem:

• Less deep, slow-wave NREM sleep: This precious sleep stage, which promotes health and memory, decreases significantly with age (by 60-90% from teenage years to age 70).
• More fragmented sleep: Older adults experience reduced sleep efficiency and more disruptions.
• Circadian rhythm regression: This can lead to earlier bedtimes and awakenings. This creates a "vicious loop" where poor sleep exacerbates toxic protein accumulation, which in turn interferes with sleep.

Strategies for Sleep Improvement

Given the critical importance of sleep, Topol advocates for various behavioural and lifestyle factors to promote healthy sleep, while also cautioning against certain interventions.

Recommended Strategies:

• Maintain regularity: Go to bed and wake up at the same time each day, including weekends.
• Regular exercise: Physical activity is consistently linked to improved sleep quality. Topol, citing Euan Ashley, a leader of the MoTrPAC initiative, emphasizes that exercise induces a multisystem, multidimensional response, positively influencing nearly every tissue and organ, which in turn supports restorative sleep.
• Optimal eating patterns: Avoid eating late at night, ideally having an early dinner at least three to four hours before bedtime. Time-restricted eating might also align meal timings with circadian rhythms, which are affected by nutrient absorption and gut hormone production.
• Create a conducive sleep environment: Ensure the bedroom is cool, fully dark, and quiet.
• Avoid blue light: Steer clear of electronic devices before bed, as blue light disrupts circadian rhythm and suppresses melatonin production.
• Address sleep apnea: If suspected, diagnose and manage sleep apnea, as it significantly disrupts sleep and is associated with increased risk of cardiovascular and metabolic diseases.
• Relaxation techniques and CBT-I: Cognitive behavioural therapy for insomnia (CBT-I) is recommended as a first-line treatment, often achievable through trained therapists or smartphone apps.
• Moderate napping: While debated, napping one to two times weekly has been linked to reduced cardiovascular events, but longer afternoon naps (over an hour) are associated with risk.

What to Avoid:

• Common sleep medications: Topol specifically cautions that drugs like Ambien (zolpidem) can suppress glymphatic flow and reduce waste disposal, potentially contributing to Alzheimer's risk. Many other sleep aids may have similar adverse effects. These medications have not been shown to improve the principal function of sleep (waste clearance) or promote deep slow-wave sleep without significant side effects.
• Alcohol: Avoid alcohol, especially within three hours of going to bed, as it can disrupt sleep.
• Supplements: Melatonin, magnesium, and ashwagandha supplements have shown only small effects for promoting sleep quality, with low-quality evidence supporting their efficacy.

The integration of lifestyle factors is critical. The "lifestyle+" concept, which Topol details in Super Agers, illustrates that optimal diet, exercise, and sleep collectively contribute to extending healthspan and mitigating the risks of age-related diseases. For instance, exercise can lower the p-Tau217 biomarker for Alzheimer's disease, suggesting that interventions can impact the progression of neurodegenerative conditions. This demonstrates the interconnectedness of these factors in maintaining brain and overall health.

Sleep's role in brain health

Drawing from sources like his new book, Super Agers, and his Ground Truths newsletter, Eric Topol underscores the absolutely vital role of sleep in maintaining brain health and, indeed, overall healthy aging. Sleep isn't just a period of rest; it's a critical biological state essential for human life, on par with the need for air, food, and water.

Here's a breakdown of sleep's role in brain health, as illuminated in the sources:

• Brain's Waste Clearance System (Glymphatics): A significant understanding of sleep's function emerged in 2012 with the discovery of the brain's glymphatic pathway by Maiken Nedergaard and her colleagues. This system acts like the brain's plumbing, similar to the body's lymphatic system but without lymph nodes, draining chemical waste and facilitating the movement of cerebrospinal fluid and interstitial fluid.

  • Synchronised Neuronal Activity: Recent findings in 2024 revealed that synchronised neuronal activity is key to activating this glymphatic waste clearance. As Nedergaard's team aptly put it, "neurons that fire together, shower together," meaning that the collective firing of neurons drives the brain's cleansing process. Blocking neuronal firing prevents waste clearance. This process involves arterial vasomotion and the release of neuronal peptide molecules.
  • During Non-REM Sleep: The sources highlight that sleep is the principal driver of glymphatic flow and waste clearance, primarily occurring during the non-rapid eye movement (NREM) phase, especially deep slow-wave sleep (stage N3). During NREM sleep, large waves of cerebrospinal fluid flow are observed, mediated by norepinephrine levels, acting as a pump.

• Clearing Toxic Proteins and Preventing Neurodegenerative Diseases: One of sleep's major functions is the clearance of toxic proteins from the brain, such as β-amyloid and tau, which are critical for brain health.

  • Alzheimer's Disease: Accumulation of β-amyloid is considered a precursor to Alzheimer's disease. Just one night of sleep deprivation has been shown to result in a substantial increase in β-amyloid accumulation in brain regions linked to Alzheimer's. Chronic poor sleep is prospectively linked to an increased risk and progression of Alzheimer's. For example, a study of nearly 8,000 participants over 25 years found that individuals aged 50-60 sleeping six hours or less had a more than 20% increased risk of developing late-onset dementia. The p-Tau217 biomarker, an early indicator for Alzheimer's, has also been shown to respond to lifestyle interventions like exercise.
  • Parkinson's Disease: Similarly, in Parkinson's disease, the accumulation of alpha-synuclein is linked to impaired waste clearance.

• Impact of Aging on Brain Cleansing: As we age, the efficiency of the glymphatic system and vascular dynamics naturally decline. Sleep also becomes more disrupted with age, characterised by more arousals, less synchronized neural activity, and a significant reduction in NREM stage 3 deep slow-wave sleep. This decline leads to the accumulation of metabolic waste, deposition of extracellular matrix, and dysfunctional brain macrophages, all contributing to a "dirty brain" that ages faster. This creates a vicious cycle, where decreased sleep leads to more toxic proteins, which in turn interfere with sleep.

• Optimal Sleep Duration: Topol highlights studies, including one from the UK Biobank with nearly 500,000 participants, indicating that about seven hours is the optimal duration of sleep. Deviations from this optimal duration, both too little (less than seven hours) and too much (more than eight hours), are associated with cognitive and mental health decline, unfavourable changes in brain structure, and heightened all-cause mortality. Each hour's decrease below the 7-8 hour threshold is linked to a 6% higher risk of total cardiovascular disease, while each hour above it is associated with a 12% higher risk.

• Sleep Medications and Supplements: Many commonly used sleep medications, such as Ambien (zolpidem), can suppress norepinephrine levels and reduce glymphatic flow, effectively backfiring on the brain's waste disposal. This inhibitory effect may explain why such medications, and other benzodiazepine-like drugs, have been associated with a heightened risk of Alzheimer's disease and dementia in multiple studies. Crucially, none of the commonly used sleep medications or supplements have been shown to improve waste clearance or promote deep slow-wave sleep without significant side effects.

• Lifestyle Recommendations for Healthy Sleep: Given the limitations of pharmacologic interventions, Topol advocates for behavioural and lifestyle factors to promote healthy sleep. These include:

  • Maintaining a regular bedtime and awakening pattern daily, including weekends.
  • Regular exercise, while avoiding late-day exertion too close to bedtime.
  • Avoiding late eating close to bedtime; an early dinner, at least 3-4 hours before bed, is recommended.
  • Avoiding alcohol, especially within three hours of going to bed.
  • Ensuring a cool, fully dark, and quiet bedroom.
  • Avoiding blue light from electronic devices, which disrupts circadian rhythm and suppresses melatonin production.
  • Diagnosing and treating sleep apnea if present, due to its association with increased risk of cardiovascular and metabolic diseases.
  • Considering relaxation training techniques or digital cognitive behavioural therapy.

In his book Super Agers, Topol categorises sleep as a crucial "lifestyle+" factor, emphasising that while seemingly "low tech," our refined understanding of its mechanisms, like the glymphatic system, has profoundly enhanced our knowledge of healthy aging. The goal is to leverage these insights to promote "brainwashing" as we age, thereby reducing the toll of neurodegenerative diseases in the future.

Eric Topol, across his recent book Super Agers and his Ground Truths newsletter, frequently underscores the profound and indispensable role of sleep in maintaining brain health, particularly regarding its critical function in waste clearance and its broad implications for cognitive function and the prevention of neurodegenerative diseases. Sleep deprivation, as he explains, directly compromises these vital processes.

Here's how sleep deprivation affects the brain, drawing on the sources:

• Impaired Waste Clearance via the Glymphatic System:

  • During sleep, particularly during non-rapid eye movement (NREM) sleep (including deep, slow-wave N3 stage), the brain's unique glymphatic system becomes highly active. This system, akin to the body's lymphatic system but without lymph nodes, is a network of fluid-filled channels, specifically involving aquaporin-4 (AQP4) expressed on astrocytes, that runs alongside blood vessels to drain chemical waste and facilitate the movement of cerebrospinal fluid (CSF).
  • This "brainwashing" function is crucial for ridding the brain of unwanted molecular waste products. As Maiken Nedergaard, a pioneer in this field, vividly put it, "It's [sleep] like turning on the dishwasher before you go to bed and waking up with a clean brain".
  • Sleep deprivation directly impairs the efficiency of this waste clearance. Even a single night of sleep deprivation in young, healthy individuals can lead to a substantial increase in the accumulation of β-amyloid protein in brain regions linked to Alzheimer's disease. This protein is a well-known precursor to the development of Alzheimer's.
  • Furthermore, synchronized neuronal activity is shown to activate glymphatic waste clearance, with "neurons that fire together, shower together". Sleep deprivation disrupts this synchronisation.
  • Norepinephrine levels mediate the cerebrospinal fluid flow during NREM sleep, acting as a pump to drive glymphatic flow.

• Increased Risk of Neurodegenerative Diseases and Cognitive Decline:

  • Chronic poor sleep is prospectively linked to the risk and progression of Alzheimer's disease. Studies, including one with nearly 8,000 participants followed for 25 years, showed that individuals aged under 50 or 60 years who consistently slept six hours or less had a greater than 20% increased risk of developing late-onset dementia. Reduced non-REM sleep, in particular, has been tied to the risk of early Alzheimer's disease.
  • As the brain ages, the efficiency of glymphatics and vascular dynamics naturally decline, and sleep often becomes more disrupted with less deep NREM stage 3 sleep and more arousals. This creates a vicious cycle: decreased sleep leads to more toxic protein accumulation (like β-amyloid and tau), and these toxic proteins, in turn, interfere with sleep.
  • The accumulation of metabolic wastes and dysfunction of parenchymal border macrophages (PBMs) in the aging brain, exacerbated by poor sleep, contribute to the build-up of unwanted molecular waste.
  • Beyond specific diseases, sleep deprivation is consistently linked to cognitive and mental health decline.

• Inflammation and Immune System Dysfunction:

  • The clearance of toxic proteins interacts with the brain's immune system, suggesting that accumulated waste can induce harm through immune mechanisms.
  • In the aged brain, diminished lymphatic drainage from the meninges is accompanied by an untoward immune response, leading to chronic inflammation, which further impairs the exit route of waste products.
  • A study in young, healthy men showed that just one night of deprived sleep, compared to full sleep, led to deleterious pro-inflammatory changes in the transcriptome, proteome, epigenome, and blood metabolites of adipose tissue and muscle. This body-wide inflammatory response likely extends to the brain.

• Impact of Microplastics:

  • Eric Topol also highlights a deeply concerning emerging threat: microplastics and nanoplastics (MNPs) accumulating in the brain. Recent studies have shown these particles in human brain cells, including in patients with brain tumours.
  • Worryingly, a new study reported MNP concentration in the brain to be 7-30 times greater than in other vital organs like the liver or kidneys, and significantly higher in the brains of people with dementia compared to healthy individuals. While causality is not yet established, this "striking accumulation" is paralleled by evidence of MNPs inciting an aggressive inflammatory response across multiple organ systems, which could contribute to neurodegenerative processes.
  • Experimental models further demonstrate that MNPs can cross the blood-brain barrier, activate the immune system, lead to stagnation of blood flow, cause blood clots in brain capillaries, and result in neurological abnormalities. This adds a significant layer of concern regarding brain health in the context of pervasive environmental toxins.

• Adverse Effects of Sleep Medications:

  • Ironically, commonly used sleep medications can interfere with these vital processes. Ambien (zolpidem), for instance, was assessed for its effect on glymphatic flow and was found to suppress the norepinephrine effect and reduce glymphatic flow, essentially "backfiring" on waste disposal.
  • Benzodiazepine-like drugs and other sleep medications have been associated with a heightened risk of Alzheimer’s disease and dementia in multiple studies, with the mechanism potentially being the impairment of brain waste clearance induced by these medications.

In essence, Eric Topol's work strongly suggests that adequate, restorative sleep is not merely a luxury but a fundamental requirement for the brain's daily maintenance, actively clearing toxic waste and preventing the accumulation of harmful proteins and substances like microplastics that contribute to aging, inflammation, and neurodegenerative conditions. Sleep deprivation undermines these essential "brainwashing" functions, leading to significant adverse effects on cognitive health and increasing the risk of severe neurological diseases.

Optimal duration of sleep

Drawing on the insights shared by Eric Topol in his book Super Agers and his Ground Truths newsletter, the optimal sleep duration for adults is a crucial aspect of maintaining overall health and preventing age-related decline.

According to Topol, a significant study from the UK Biobank, which involved nearly 500,000 participants, provides a principal finding on this matter. This extensive research, which included brain imaging for 48,000 participants and a 6-to-10-year follow-up for 156,000 individuals, concluded that about seven hours is the optimal duration of sleep.

It is particularly noteworthy that the relationship between sleep duration and health is not linear. Topol points out that:

• Less than optimal sleep: A sleep duration of six hours or less for individuals aged 50 to 60 years was associated with a 30% increased risk of dementia in a study with nearly 8,000 participants followed for 25 years. Furthermore, every one-hour decrease in sleep below the seven-to-eight-hour threshold is linked to a 6% higher risk of total cardiovascular disease.
• More than optimal sleep: Surprisingly, sleeping beyond seven hours also showed consistent signs of cognitive and mental health decline, as well as unfavourable changes in brain structure. Long sleep, defined as more than eight hours, was associated with a heightened all-cause mortality (approximately 30%) in a study of nearly 1.4 million people. Every one-hour increase in sleep duration above the seven-to-eight-hour threshold is linked to a 12% higher risk of total cardiovascular disease.

Topol's work, especially in Super Agers, underscores that sleep is a "non-negotiable biological state required for the maintenance of human life," paralleling our needs for air, food, and water. The evidence collectively supports seven hours as the sweet spot for sleep duration to promote healthy aging and mitigate various health risks.

How sleep deprivation profoundly affects the brain

Eric Topol, author of Super Agers, frequently underlines the profound importance of sleep as a "non-negotiable biological state required for the maintenance of human life," equating its necessity to that of air, food, and water. Indeed, a good night's sleep offers a "magical sense of restoration and wellness". However, when sleep is disrupted or deprived, the consequences for brain health can be quite severe, contributing to what Topol refers to as "dirty brains that age faster".

Here's how sleep deprivation profoundly affects the brain, according to the sources:

• Impaired Brain Waste Clearance

  • Glymphatic System Dysfunction: During non-rapid eye movement (NREM) sleep, especially the deep, slow-wave (Stage N3) phase, the brain's glymphatic system—a network of fluid-filled and water channels—actively clears metabolic waste products. This "brain's plumbing system" is crucial for draining chemical waste and facilitating cerebrospinal fluid movement. Sleep is the "principal driver" of this waste clearance.
  • Accumulation of Toxic Proteins: Just one night of sleep deprivation can lead to a substantial increase in beta-amyloid accumulation in brain regions linked to Alzheimer's disease, as shown by PET scanning. This protein, along with tau, aggregates to form plaques and tangles, which are precursors to Alzheimer's disease. Chronic poor sleep is prospectively linked to the risk and progression of Alzheimer's disease.
  • Bidirectional Vicious Loop: Decreased sleep not only leads to more toxic proteins but also, these toxic proteins interfere with sleep, creating a "vicious loop" that accelerates brain aging.

• Increased Risk of Neurodegenerative Diseases

  • Alzheimer's and Dementia: Studies have shown that sleeping six hours or less at ages 50 to 60 is associated with a 30% increased risk of dementia. In a large cohort, people aged less than 50 or 60 years with 6 hours of sleep or less had a greater than 20% increased risk of developing late-onset dementia.
  • Brain Aging: As we age, the efficiency of the glymphatics and vascular dynamics declines, and sleep becomes more disrupted, with less NREM deep slow-wave sleep. This leads to the accumulation of metabolic waste and progressive dysfunction of parenchymal border macrophages (PBMs).
  • Impact on Biomarkers: Exercise, a key component of Topol's "lifestyle+" framework, has been shown to reduce plasma p-Tau217 levels, a biomarker for Alzheimer's disease, which is dynamic and responds to interventions. This suggests that improving lifestyle factors, including sleep, could potentially alter the course of neurodegenerative conditions.

• Cognitive and Mental Health Decline

  • Beyond the risk of dementia, poor sleep negatively impacts overall cognition and mental health. Optimal sleep duration, around seven hours, is crucial, as both shorter and longer durations are associated with consistent signs of cognitive and mental health decline.
  • Sleep Fragmenation and Circadian Rhythm Disruption: Older adults particularly face challenges with less deep sleep, more fragmented sleep, and regression of circadian timing, leading to earlier bedtimes and awakenings. The disruption of meal timing can also desynchronize the body's peripheral clocks, inducing glucose intolerance and affecting immune cells in the gut and inflammatory response.

• Detrimental Effects of Sleep Medications

  • Paradoxically, commonly used sleep aids like Ambien (zolpidem) can suppress the norepinephrine effect and reduce glymphatic flow, essentially "backfiring" on the brain's waste disposal system. This mechanism may contribute to the heightened risk of Alzheimer's disease and dementia associated with Ambien and other benzodiazepine-like sleep medications in multiple studies.

In essence, Eric Topol's work highlights that healthy sleep is a cornerstone of a robust "lifestyle+" approach to healthy aging. The intricate mechanisms of brain waste clearance underscore why adequate and quality sleep is not merely restorative but vital for preventing the accumulation of toxic substances that drive brain aging and neurodegenerative diseases.