This article reviews two significant scientific studies. One, published in Nature, explores the role of mitochondria in sleep regulation. Through research on fruit flies, it reveals that mitochondrial function changes, especially those related to respiration and ATP synthesis, are crucial for the generation of sleep need. Manipulation of mitochondrial dynamics can directly affect sleep duration and depth. The other study, published in Cell, focuses on the relationship between mitochondria and lifespan. By comparing multiple mammalian species and analyzing within - species differences, it shows that mitochondrial - related gene expression patterns are associated with lifespan, and enhancing mitochondrial function can potentially delay aging. Overall, these studies highlight mitochondria as a key factor in both sleep regulation and lifespan determination, and future research in this area may lead to new insights for improving human health.
In the hustle and bustle of our daily lives, we've all likely had those moments - deadlines looming, adventures calling, or simply binge - watching that addictive series. And there it is, that pesky feeling of sleepiness creeping in, making us wish there was a simple "off" switch for sleep. Conversely, for those plagued by insomnia, a "sleep - on" button would be a dream come true. Well, as it turns out, the key to this sleep "switch" might be hidden within some of the tiniest components of our cells - mitochondria.
Mitochondria: The Sleep - Regulating Switch
A recent study published in Nature titled "Mitochondrial origins of the pressure to sleep" has shed new light on the connection between our sleep needs and mitochondria. Sleep is an essential physiological process for all living organisms. However, the exact reasons why we need sleep and how the sleep drive is generated have long puzzled the scientific community. In this research, a team from the University of Oxford delved deep into the sleep - regulating mechanisms of fruit flies to uncover the role of mitochondria.
DOI: 10.1038/s41586-025-09261-y
The team hypothesized that the need for sleep could be closely linked to the functional state of mitochondria, particularly processes related to mitochondrial respiration and ATP synthesis. To explore the molecular basis of sleep need, they first conducted single - cell transcriptome sequencing on the brains of fruit flies that had either been sleep - deprived or had normal rest. Using fluorescent labeling techniques, they specifically enriched sleep - regulating neurons that project to the dorsal fan - shaped body (dFBNs) and compared them with other types of neurons. Through high - throughput sequencing, the researchers obtained the gene expression profiles of these neurons in both sleep - deprived and normal - rest states.
Subsequently, with the help of bioinformatics tools, the team analyzed the changes in gene expression in dFBNs neurons after sleep deprivation. They discovered that genes upregulated after sleep deprivation were almost all those encoding proteins related to mitochondrial respiration and ATP synthesis, while downregulated genes mainly involved synaptic transmission and neuronal excitability. This finding strongly suggests that changes in mitochondrial function could be a crucial factor in the increased need for sleep.
Figure: Mitochondrial electron excess induces sleep
The researchers then observed the morphological changes in mitochondria within dFBNs neurons of fruit flies after sleep deprivation. They found that sleep deprivation led to an increase in mitochondrial fragmentation, more contact points between mitochondria and the endoplasmic reticulum, and enhanced mitophagy. These morphological changes are closely associated with alterations in mitochondrial function.
To further investigate the impact of mitochondrial dynamics on sleep, the team used gene - editing techniques to specifically manipulate the expression of proteins related to mitochondrial fission and fusion in dFBNs neurons. The experimental results clearly showed that promoting mitochondrial fission reduced sleep, while promoting mitochondrial fusion increased sleep. This directly proves the important role of mitochondrial dynamics in sleep regulation.
In addition, the research team also used fluorescent ATP sensors and electrophysiological recording techniques to monitor the effects of sleep deprivation and mitochondrial dynamics manipulation on ATP concentration and electrophysiological properties in dFBNs neurons. They found that sleep deprivation led to an increase in ATP concentration in dFBNs neurons, while promoting mitochondrial fission decreased ATP concentration and reduced neuronal excitability. These results further support the close link between mitochondrial function and sleep need.
In summary, through a series of experiments, the research team reached a clear conclusion: after sleep deprivation, the upregulated genes in dFBNs neurons mainly encode proteins related to mitochondrial respiration and ATP synthesis, indicating that sleep deprivation may trigger a compensatory response in mitochondria to meet increased energy demands. The morphological changes such as increased mitochondrial fragmentation, more endoplasmic reticulum contact points, and enhanced mitophagy also suggest that mitochondria play a key role in the generation of sleep need. Moreover, by manipulating the expression of proteins related to mitochondrial fission and fusion, they were able to directly affect the duration and depth of sleep, providing new molecular targets for sleep regulation.
Figure: Sleep history alters mitochondrial dynamics
Mitochondria and the Secrets of Longevity
The wonders of mitochondria don't stop at regulating sleep; they are also intricately linked to the length of our lives. You may have heard the saying, "Why sleep for a long time during life when you will sleep forever after death?" In reality, both the "long sleep" during life and the "forever sleep" after death seem to be closely related to mitochondria.
In the field of biology, the length of lifespan has always been a topic of great interest to scientists. From small rodents with a lifespan of only a few years to large whales that can live for over two centuries, there is a huge difference in lifespan among species. Even within the same species, there are significant differences between long - lived and short - lived individuals. Naked mole - rats, certain bats, and humans, with their unusually long lifespans, have become the focus of scientific research. Recently, a research team from Harvard Medical School published a study in Cell titled "Distinct longevity mechanisms across and within species and their association with aging", revealing the crucial role of mitochondria in lifespan regulation.
DOI: 10.1016/j.cell.2023.05.002
The research team first performed RNA sequencing on multiple tissues of 41 mammalian species, ranging from the short - lived shrew to the long - lived bowhead whale, which have a wide lifespan span. After analyzing these data, the scientists found that there were significant differences in the expression patterns of mitochondrial - related genes between long - lived and short - lived species. Specifically, genes related to mitochondrial translation and the respiratory chain were upregulated in long - lived species, while genes related to protein degradation and the TCA cycle were downregulated.
This discovery implies that long - lived animals may optimize mitochondrial function, reducing energy metabolism losses and damage, thereby delaying the aging process. For example, the bowhead whale, which can live over 200 years, shows highly efficient regulation of energy metabolism in its mitochondrial gene expression pattern.
In addition to cross - species comparisons, the research team also explored the differences in lifespan among individuals within the same species. They found that even in long - lived species like humans, there are significant differences in mitochondrial function among different individuals. By analyzing mouse models, the scientists confirmed that regulating the expression of mitochondrial - related genes through gene - editing techniques can significantly affect the lifespan of mice.
For example, inhibiting the IGF1 (insulin - like growth factor 1) signaling pathway can extend the lifespan of mice and improve their health, and this pathway is closely related to mitochondrial function, further verifying the central role of mitochondria in lifespan regulation. Interestingly, longevity interventions such as rapamycin and calorie restriction can also extend lifespan by affecting mitochondrial function.
Graphical abstract
Aging is a complex biological process involving the gradual decline of multiple systems and organs. Mitochondria, as the "energy hub" within cells, play a crucial role in this process. As we age, mitochondrial function gradually declines, leading to insufficient energy supply and the accumulation of cell damage. This damage not only affects the normal function of cells but also triggers a series of inflammatory responses and oxidative stress, further accelerating the aging process.
However, studies have also found that enhancing mitochondrial function can slow down the aging process. For example, by supplementing with mitochondrial protectants such as NAD+ (nicotinamide adenine dinucleotide), the energy metabolism efficiency of mitochondria can be improved, oxidative stress and inflammatory responses can be reduced, thus extending lifespan and improving health.
In conclusion, this research not only reveals the mysteries of mitochondria in lifespan regulation but also provides new ideas for the development of anti - aging drugs and interventions. For example, by regulating the expression of mitochondrial - related genes or supplementing with mitochondrial protectants, we may be able to delay the aging process, improve the quality of life, and extend the healthy lifespan.
Conclusion
In conclusion, the two research papers discussed above, from different physiological processes (longevity and sleep), confirm the view that "mitochondrial function is the core hub for regulating the homeostasis of living organisms." The pressure for sleep stems from the imbalance of homeostasis caused by abnormal mitochondrial function, and the mechanism of longevity also depends on the optimization of mitochondrial metabolism to delay aging. This connection suggests that the regulation of mitochondrial function may be the key node linking "sleep" and "aging." Truly, mitochondria, despite their small size, possess great power.
In the future, with the continuous deepening of mitochondrial research, we will gradually uncover the secrets of aging and longevity hidden within these tiny structures, contributing scientific strength to unlocking new ways for human health and longevity. Let's look forward with anticipation and witness more breakthroughs and discoveries in this field.