Most people know that melatonin is an important hormone for regulating sleep, but did you know that melatonin might have the potential to slow down the ageing process? This is the topic of a recent paper in Rejuvenation Research. In this paper, authors discuss how melatonin is important not only for regulating sleep, but also several other important processes related to ageing, and speculate that supplemental melatonin might be useful for preventing and managing age-related diseases.
Melatonin is known to most as the ‘sleep hormone’, but what exactly is it doing? While we are not consciously aware of it, a brain region called the suprachiasmatic nucleus (SCN) continuously tracks the time of day using a system called the master clock. The master clock goes through a roughly 24 hour cycle that regulates many aspects of our biology based on the time of day. This 24 hour cycle is known as the circadian rhythm and is maintained even when we are not consciously aware of the time. It is the reason we get jet lag – the master clock prevents us from sleeping during the night, because it is still aligned to the old day/night cycle, and is signalling that the body should be awake.
Melatonin is, simply put, the chemical that tells the body that it should be asleep. It exists in a two way relationship with the master clock. Melatonin is produced during the dark and suppressed by light and helps keep the master clock properly aligned with the day/night cycle. This is why taking melatonin at night helps with jet lag – it helps the master clock sync up with the new day/night cycle faster. It’s also why seeing too much light in the evening, or too little in the morning, can be so detrimental to sleep quality.
So, how might melatonin protect against the ageing process? The authors of the paper outline three main benefits of melatonin outside of sleep regulation:
Reduced oxidative stress
Oxidative stress is a term used to describe an imbalance between reactive oxygen species (ROS) and antioxidants. ROS are molecules produced by our metabolism that can damage other important molecules like proteins and DNA. To protect against this, our cells produce antioxidants that neutralise ROS and protect valuable cellular components from damage. As we age, ROS production starts to outstrip our antioxidant capacity, and this is thought to be a contributor to general ageing and age-related disease.
Melatonin is not only a powerful antioxidant by itself, it also activates other antioxidants. It’s good at crossing cell membranes, meaning it can effectively protect deeper components of a cell.
Protecting and repairing
Melatonin enhances and protects another important molecule called NRF2. NRF2 controls the activity of a number of important genes. In particular, NRF2 protects cells against inflammation and enhances the destruction of damaged cellular components. This ‘housekeeping’ process, in which structures that no longer work properly are degraded and recycled, is important for protecting against age-related disease. The authors suggest that the interaction between melatonin and NRF2 could have many benefits including protection against cardiovascular disease, neurodegeneration and cancer.
As we have all heard a hundred times, the mitochondria are the power plants of the cell, but they also play an important role in the ageing process. As we grow older, our mitochondria become increasingly ‘leaky’ and inefficient. These dysfunctional mitochondria are also a major source of the ROS we mentioned earlier.
Melatonin seems to be concentrated within the mitochondria – levels of melatonin in the mitochondria have been found to be higher than those in the blood. Melatonin enhances the efficiency of the mitochondria, which also reduces the amount of ROS byproducts they produce. Another important benefit of melatonin is that it enhances the destruction and recycling of defective mitochondria. This function of melatonin has the potential to be very beneficial for delaying the progression of ageing, because dysfunctional mitochondria are considered to be key players in many age-related diseases. They also promote senescence, another important component of the ageing process in which cells are no longer able to divide.
Preserving the circadian rhythm
Of course, melatonin’s primary role is in regulating sleep, which seems to play a crucial role in the ageing process. The authors note that beyond the 6th decade of life, the amount by which melatonin levels vary over the course of a day declines, probably contributing to disruption of the circadian rhythm and less/poorer quality sleep in older people.
While we still don’t fully understand the relationship between sleep and the ageing process, we do know that sleep deprivation has a devastating effect on health, and that there is a strong correlation between sleep disturbance and age related diseases. Studies suggest that melatonin can extend lifespan in animals and is effective in humans for correcting circadian rhythm disturbances. So, the effects of melatonin on sleep patterns alone make it worthy of investigation as an age-delaying drug.
The take-home message:
Supplemental melatonin can not only address sleep disturbances, but also combats some processes thought to be fundamental to ageing including inflammation, oxidative stress, mitochondrial dysfunction and senescence. However, there are many ways to enhance your body’s natural ability to produce melatonin. The most important practice is to control how much light you are exposed to throughout the day. Specifically, see as much sunlight as possible soon after waking, and limit how much artificial light you receive during the evening. For a full guide on how to optimise your sleep for longevity, check out our series on the subject.
Title image by Kate Stone Matheson, Upslash
Crosstalk Between Aging, Circadian Rhythm, and Melatonin https://doi.org/10.1089/rej.2023.0047