In the first article in this series, Why You Wake at 2:17 a.m., we looked at what disrupts sleep: the CO₂ instability loop that pulls you to the surface at the same time every night, and why the brainstem’s set point changes slowly. In this article we go deeper into what deep sleep is actually doing while it runs, and why the quality of that sleep matters far more than many of us realize.
A discovery nobody saw coming
For most of scientific history, the brain was considered an anomaly. Every other organ in the body has a lymphatic system: a network of vessels that drain waste, clear metabolic byproducts, and maintain the chemical environment cells need to function. The brain, surrounded by its protective barrier, appeared to have no equivalent. Scientists assumed it simply managed differently.
In 2012, neuroscientist Maiken Nedergaard and her team at the University of Rochester discovered it does not manage differently at all. It has its own system. They named it the glymphatic system, after the glial and lymphatic support cells that make it possible[1].
The simplest way to understand it is this: while the brain is awake, it is like a busy kitchen in constant use. Dishes pile up. Metabolic waste accumulates between cells. There is no time to clean. Sleep is when the dishwasher finally turns on.
What happens when the dishwasher runs
During deep, slow-wave sleep, something remarkable happens. The spaces between brain cells expand by up to 60 percent[2]. This is not a side effect of sleep. It appears to be one of its purposes. With those spaces widened, cerebrospinal fluid flows through channels that were too narrow to use during waking hours, flushing out metabolic waste and carrying it toward the body’s drainage system.
Among the substances cleared every night are amyloid-beta and tau: proteins that, when allowed to accumulate over years and decades, are strongly associated with Alzheimer’s and Parkinson’s disease[1,2]. The glymphatic system does not wait for damage to occur. It runs maintenance every night, as a matter of routine, the way a dishwasher runs after dinner. A 2026 clinical trial with 39 human participants confirmed this directly: normal sleep increased morning blood levels of Alzheimer's biomarkers compared to sleep deprivation, consistent with active overnight clearance[8].
This reframes what sleep deprivation actually means. A bad night is not just fatigue the next day. It is a night the dishwasher did not finish. One interrupted cycle will not cause lasting harm. But the consequences of decades of shallow, fragmented sleep, decades in which the cleaning cycle kept getting interrupted, are now beginning to be understood.
What switches the dishwasher on
The glymphatic system does not run simply because the brain is asleep. It needs a specific chemical environment to engage. And the signal that creates that environment will be familiar from the first article in this series.
As breathing slows during sleep, less CO₂ is exhaled. It accumulates in the blood. Arterial CO₂ rises by approximately five to 15 percent above waking levels during healthy sleep[3,4,5]. That rise widens blood vessels in the brain, improving circulation and creating the conditions the glymphatic system needs to operate. Without that gentle CO₂ rise, the cleaning cycle never fully engages.
This is the same CO₂ rise we explored in the first article, in the context of the 2am waking pattern. There, CO₂ dropping too low was the problem. Here, CO₂ rising high enough is the requirement. The two articles are describing the same mechanism from different angles: CO₂ stability during sleep is not just about staying asleep. It is about what the brain can accomplish while sleep runs undisturbed.
In 2025, a research team led by neuropsychologist Sephira Ryman took this further. They found that brief, controlled increases in CO₂ inhaled while awake stimulated glymphatic clearance in both healthy adults and people with Parkinson’s disease. Cerebrospinal fluid movement increased. Markers of toxic proteins appeared in the blood, suggesting waste was being actively cleared from the brain[6]. CO₂ does not merely correlate with the cleaning cycle. It appears to help activate it, even outside of sleep.
What fragmentation does to the cycle
Every time the brain surfaces during the night, the cleaning cycle stalls. CO₂ drops as breathing destabilises. Blood vessels constrict. The widened spaces between brain cells begin to close. When sleep resumes, the system tries again. If the next arousal comes, it stalls again.
For people who wake repeatedly through the night, this is what is happening in the background. The dishwasher is not broken. It is being interrupted before it can finish. And unlike a kitchen dishwasher that simply picks up where it left off, the glymphatic system is most active in the deepest stages of sleep, the stages that are hardest to reach and easiest to lose[7].
This is what 30 years of fragmented sleep meant for Catharina, who opened the first article in this series. Every one of her five to 10 nightly awakenings was a cycle interrupted. The system kept trying to clean. And kept being told to stop.
What this means in practice
Three conditions consistently support the cleaning cycle, and they will feel familiar.
Reaching deep sleep is where the work happens. Light, fragmented sleep keeps the dishwasher running at reduced capacity. Everything that supports deeper, more stable sleep supports the cleaning cycle: nasal breathing during the day, regular low-intensity movement, a nervous system that is not running on chronic low-level activation.
Allowing CO₂ to rise during sleep is the specific requirement. Slow nasal breathing through the night keeps CO₂ from dropping, blood vessels from constricting, and the conditions from collapsing. The mechanism is the same one that determines whether you surface at 2am or stay under.
Building CO₂ tolerance during the day may do more than improve sleep. The 2025 Ryman study suggests that raising CO₂ levels while awake can activate glymphatic clearance directly. The cleaning cycle, it turns out, is not exclusively nocturnal. Consistent nasal breathing practice, breathing retraining, and regular exercise while breathing through the nose all build the CO₂ response the brain appears to need, day and night.
What comes next
This is the second of three articles on sleep and CO₂.
The third is a first-person account: what 10 days of forced mouth breathing did to Anders’s adrenaline levels, mood, cravings, and sleep quality, and what happened the night it stopped. It is one of the most striking pieces of self-experimentation in the breathing field, and it makes everything in these first two articles suddenly very concrete.
References
[1] Iliff JJ, Wang M, Liao Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid-beta. Sci Transl Med. 2012;4(147):147ra111.
[2] Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):373–377.
[3] Midgren B, Hansson L. Changes in transcutaneous PCO₂ with sleep in normal subjects and in patients with chronic respiratory diseases. Eur J Respir Dis. 1987;71(5):388–394.
[4] Douglas NJ, White DP, Weil JV, Pickett CK, Zwillich CW. Hypercapnic ventilatory response in sleeping adults. Am Rev Respir Dis. 1982;126(5):758–762.
[5] Berthon-Jones M, Sullivan CE. Ventilation and arousal responses to hypercapnia in normal sleeping humans. J Appl Physiol. 1984;57(1):59–67.
[6] Ryman SG, Vakhtin AA, Caprihan A, et al. The influence of intermittent hypercapnia on cerebrospinal fluid flow and clearance in Parkinson’s disease and healthy older adults. npj Parkinson’s Dis. 2025;11(1):334.
[7] Bae H, Park I, Joo EY. Assessment of effects of carbon dioxide exposure on sleep stability in insomnia. J Sleep Med. 2024;21(1):44–50.
[8] Dagum P, Elbert DL, Giovangrandi L, et al. The glymphatic system clears amyloid beta and tau from brain to plasma in humans. Nat Commun. 2026;17:715.
The information in this article is for educational purposes only and does not constitute medical advice. If you have a diagnosed sleep disorder or are currently using medical equipment to manage your sleep, please consult your healthcare provider before making changes to your treatment.
