Lack of sleep opens a Pandora’s box for metabolism, damaging cardiovascular health and memory

Sleep is like a kind of reset for the body. A reboot of the human operating system, where cells take advantage of the opportunity to rest, replenish, or repair themselves. It’s an essential function for life, and when it fails, a difficult-to-close Pandora’s box of health problems opens. A scientific review published Tuesday in the journal Science Signaling has focused on the metabolic effects that lack of sleep has on the body and has found that this deprivation of a vital function has a direct impact on the health of the entire body, including the brain: according to the authors, poor sleep alters the metabolic functioning of many cells, including neurons, and this also has an impact on cognition and long-term memory. The metabolic effects described by lack of sleep are similar to those observed in neurodegenerative diseases, such as Alzheimer’s.

Losing a night’s sleep, therefore, doesn’t just leave a person with temporary tiredness or a bad mood. The impact can be much deeper. Insomnia (understood as sleeping less than five hours or having broken sleep, according to experts) has already been associated with an increased risk of obesity, cardiovascular disease, and type 2 diabetes, all of which are linked to metabolic dysfunction — that is, an imbalance in the body’s processes for producing and using energy and staying healthy. The new study delves into this relationship between insomnia and metabolism and concludes that, in situations of sleep deprivation, some cells prioritize allocating their energy expenditure to cell survival, which causes a fuel shortage to power other “metabolically demanding” but non-essential activities, such as the formation of long-term memory.

When sleep is insufficient, the body’s metabolism is turned upside down. Energy homeostasis — the balance between energy intake and energy expended for the body to function properly — is deregulated, triggering a kind of domino effect in which some vital processes begin to fail. For example, explains Ana Fortuna, coordinator of the Sleep Unit at Sant Pau Hospital in Barcelona, “glucose is not eliminated properly, there is an alteration in the hormones that regulate satiety, inflammation and oxidative stress are promoted...” And all these metabolic alterations can have cardiovascular and neurodegenerative repercussions.

The authors of the scientific review, a group of scientists from Saint Joseph’s University (United States), have analyzed the evidence on the impact of this metabolic disruption on different parts of the body, from circadian rhythms and heart and liver cells to neurons. Nothing is immune to the effects of insomnia. Not even brain cells.

Sleep is, in the words of neurologist and sleep expert Alejandro Iranzo, “like a recycling bin, with memories you either throw away or store.” It’s a time the brain uses to discard unimportant memories. It’s also a time to enhance learning and consolidate relevant memories stored during waking hours. During sleep, there is also a kind of sweeping of toxins that accumulate on the brain’s highways, a key hygiene system for maintaining neurological health. A sleep disturbance hits this brain cleansing mechanism hard and completely alters the energy balance of an organ that has particularly high fuel needs to function — the brain consumes approximately 20% of the body’s total oxygen and 25% of its total glucose intake to maintain normal function.

Relationship with neurodegeneration

Researchers explain that the impact of imbalances caused by insomnia varies across different cell types. However, they point out that in some cells with high metabolic activity, such as neurons, lack of sleep alters their functioning and impairs, for example, energy-intensive processes, such as the creation of synapses — connections between neurons. These metabolic changes due to lack of sleep are similar to those observed in neurodegenerative diseases, such as Alzheimer’s or Parkinson’s.

In a way, decreased sleep duration, impaired metabolic function, and neurodegeneration are interconnected. In fact, sleep disorders, such as apnea and REM sleep disorders, are early markers of neurodegenerative diseases such as Parkinson’s and Lewy body dementia. “Insomnia has been characterized as a risk factor for neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease; and it is also correlated with an increased risk of hypertension, hyperglycemia, and obesity. In both Alzheimer’s and Parkinson’s patients, sleep disturbance occurs before the onset of other symptoms and is associated with a greater symptom burden. Surprisingly, the metabolic profiles of Alzheimer’s and Parkinson’s are similar to those observed after sleep deprivation, especially in relation to energy production and oxidative stress,” the scientists reflect in the article.

The authors believe that these similarities "could indicate" that all of these conditions have underlying metabolic mechanisms. "After sleep deprivation, there is evidence of a negative energy balance and increased oxidative stress in neurons and glia [another type of brain cells]. These same effects are observed in Alzheimer's and Parkinson's at the pathological level, ultimately resulting in severe mitochondrial dysfunction and cell death." The authors consider it "imperative" to accurately understand the metabolic consequences of sleep deprivation in order to prevent and treat these and other neurodegenerative disorders. "The extreme metabolic changes observed in neurodegenerative disorders would suggest that the metabolic consequences of sleep loss accumulate over time," they add.

Lost sleep is not recovered

The long-term metabolic repercussions of continued sleep loss are unclear. What scientists do know is that sleep is not easily recovered. One example: sleep deprivation modulates hippocampal sharp waves, a crucial element for memory consolidation and retrieval. “In humans, two nights of recovery sleep are not sufficient to fully recover the memory or hippocampal connectivity deficits observed after a single night of total sleep deprivation. Therefore, a single episode of sleep loss can lead to lasting metabolic effects, impairing the ability to recover from further sleep loss,” the scientists note in the article.

María José Martínez Madrid, coordinator of the chronobiology working group at the Spanish Sleep Society, argues that, at most, “you can recover the sleep from one or two nights ago.” No more. “The metabolic damage from accumulated sleep deficit or the accumulation of toxins cannot be cleared,” she warns. And that has consequences, although the real long-term impact is unclear, she admits: “Less is known about sleep than about the surface of Mars. We still need to understand what exactly happens while we sleep and the long-term consequences of not doing so.” The Spanish Neurological Society estimates that between 20% and 48% of the population has sleep problems.

In any case, there’s no doubt about the shock that lack of sleep can have on the body. The metabolic imbalance is such that the authors of the scientific review have chosen a suggestive title for their article and directly define lack of sleep as a “metabolic disorder” in itself.

Martínez Madrid slightly disagrees and clarifies that, rather, it would be more pertinent to say that “sleep loss acts as a precipitating factor or a causal mechanism that leads to metabolic disorders.” When faced with sleep deprivation, she explains, “the body goes into saving mode, burns energy less efficiently, and promotes fat storage.” “In the long term, these disorders can contribute to the development of obesity or type 2 diabetes. Although saying that sleep loss is a metabolic disorder may sound shocking, in my view, the most accurate statement is that sleep deprivation acts as a powerful trigger for metabolic imbalances,” reflects the scientist, who did not participate in the study.

Fortuna, on the other hand, defends this provocative point: “What they intend is for importance to be given to sleep deprivation. For sleep to be valued the same way you value sugar. Insomnia is a trigger, but it’s at the heart of many mechanisms.”

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