I’m betting by now many of my readers are familiar with the standard melatonin story – it’s the hormone secreted by the pineal gland deep inside your brain that regulates the body’s sleep/wake cycle, aka our circadian rhythm. And most of you have heard about the mitochondria, the “power plants” inside our cells where fuel – mostly glucose and fatty acids – is combusted into the energy – ATP molecules – that runs the body. 

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However, you may not be up on more recent research uncovering the connection between the two “M”s – melatonin and mitochondria, which helps explain a lot about how and why our body ages. For starters, most of the body’s melatonin supply is actually produced inside the mitochondria, think of it as the oil that keeps the car engine running smoothly. And with age, not only does that engine (mitochondria) put out less power, and generate more exhaust (metabolic waste), but the oil levels (melatonin) drop as well. That creates a vicious cycle that, with the passing of the decades, make us look and feel older, not to mention becoming more prone to chronic disease. But when we really understand what’s going on, we have the tools and the opportunity to start to push back. How to get the ball rolling? Here’s what you need to know: 

So, how does melatonin affect our energy? 

First a caveat: most of the research has been done in the lab, not in humans. But the picture that’s emerging is fascinating, important and potentially life-altering in a good way. Let’s go inside the mitochondria that live inside most of our cells. It’s walled off from the rest of the cell inside its own membrane layers. With age, that membrane begins to dissolve, allowing stored mitochondrial DNA to leak into the rest of the cell. That in turn triggers the production of “reactive oxygen species, or, in plainer English, “free radicals” which further eat away at the mitochondria and generate more damage, yet another vicious cycle. 

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Some of this damage is an inevitable part of the aging process, and mitochondrial dysfunction is one of the chief “hallmarks of aging.” But the more melatonin our bodies can make, the more we can limit the fall-out. By shoring up the mitochondrial membranes, it helps slow down free radical production and helps apply the brakes to other nasty things leaky mitochondria can do, like encouraging cells to die (apoptosis) before their time and interfering with the making of new cells. Sometimes, the damage escapes into the rest of the body, when old mitochondria influence old cells not to die when their time should be up. They become “senescent.” So, instead of doing their normal jobs, they secrete inflammatory molecules – cytokines --that travel the bloodstream stirring up trouble. 

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Part of the job description of the melatonin produced by the pineal gland, circulating throughout the body as a hormone, is to help neutralize this threat – they’re anti-inflammatory antioxidant scavengers. As if all this damage-control wasn’t enough, melatonin also helps the cellular power plants do what they’re supposed to do more efficiently, that is, produce the ATP energy that drives the entire system. 

The aging brain: running on empty? 

There are a lot of reasons we can’t run a mile at age 50 or 60 as swiftly as we could in our teens. (Or run one at all.) But having the mitochondria in our muscle cells shrink and grow sloppy is part of the story, aided and abetted by the corresponding decline in our melatonin levels. However, for most of us, what’s more essential is being able to think clearly and having a memory we can trust. Safe to say we’d all like to hold on to that for as long as humanly possible. But the brain is where the drop in mitochondria and melatonin can really do a number on us. 

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As we age, inflammation progressively injures the brain as we miss more and more of the buffering effect of our youthful melatonin levels. But what’s less widely appreciated is that the brain is an energy-hungry organ, on average, accounting for about 2% of our body mass but 20% of our total energy consumption. (Our heart, muscles, and kidneys also have big energy appetites and consequently are also vulnerable to age-related mitochondrial dysfunction.) 

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As older mitochondria pump out less ATP and more metabolic garbage, our brains literally become underpowered, and more vulnerable to functional decline. Most people by their 80s will have some degree of at least mild cognitive impairment and about a third will have Alzheimer’s disease. How much of a causal role the drop in melatonin plays here isn’t known. But the stats suggest a plausible connection. On average, eighty-year-olds have melatonin levels three to four times lower than teenagers, and people with Alzheimer’s have levels seven times lower than their counterparts who don’t suffer from the condition. 

Defending your melatonin…and your mitochondria.

For both your melatonin and mitochondria, the strategy is to postpone the day when either of the “M”s decline below some functional threshold and you’ve lost capacity – be it everyday energy or muscular strength or cognitive sharpness – that you’ll never get back. But, conveniently for us, what’s good for one M is generally good for the other. 

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One of the most impactful lifestyle changes you can make, which affects melatonin directly and mitochondria indirectly, has to do with the sleep/wake cycle, aka your circadian rhythm. Yes, you may have heard me talk about powering down in the evening and staying away from screens anywhere near bedtime, to cue the pineal gland to secrete the melatonin that prepares the body for sleep. But it’s the proper daily rhythm of dark and light that locks the body into hormonal health mode. 

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In practical terms, that means getting outside and taking in the bright early morning sunshine which stimulates our primary energy hormone, cortisol, the yang to melatonin’s yin. A brisk 30-60 minute walk would be great (the aerobic exercise also builds up your mitochondria, a double benefit!) but even 10 minutes in the sun can meaningfully enhance your sleep. 

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As our melatonin levels drop with age, we want to do everything in our power to protect that good night’s sleep which, yes, becomes more challenging to come by. Besides honoring our natural circadian rhythms, that means maintaining the same sleep schedule (even on the weekends) and laying off the alcohol and coffee. It’s during the deep, restorative phase of sleep that the brain clears out the day’s accumulation of metabolic wastes, much of it produced by the mitochondria in the brain cells. This “glymphatic” system helps protects the brain from neurodegenerative diseases like Alzheimer’s which becomes more and more common as we age. (It's no accident that night shift workers, whose sleep schedules are topsy turvy, suffer much higher disease rates than the rest of us, including a 1.5 times higher risk of Alzheimer’s. For good measure, healthy sleep habits keep a lid on the chronic stress that can eat away at the mitochondria, giving your mitochondria a chance to reset and repair. It’s all connected! 

Good stress vs. bad stress.

Just as bad stress (chronically elevated cortisol levels) can eat away at the mitochondria, good stress, what we call hormesis, does the opposite. Exercise is the perfect example. While unremitting hard-care endurance exercise can leave you stressed out, and your immune system washed-out, moderate aerobic activity provides a fine mitochondrial tonic. And upping the challenge, for short bursts, as in resistance training or HIIT (high-intensity interval training) can provide an even stronger boost, increasing both the number and size of your mitochondria. Along with minding our circadian rhythms, exercise, and physical activity in general, is our most powerful ally when it comes to a good night’s sleep.

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The same health-stress principle applies, if not as dramatically, to other forms of metabolic (mild) shock therapy, for instance cold or heat therapy (think cryotherapy/ice baths and saunas, especially infra-red saunas). Intermittent fasting or time-restricted eating provides a different kind of metabolic stress. The body responds by becoming metabolically more efficient, sharpening up the insulin response and stimulating autophagy, the recycling of old warn-out cell parts for new ones.  

Consuming your “M”s.

When it comes to mitochondria, antioxidant-rich foods are the ticket, especially foods rich in polyphenols, like berries, dark leafy greens and green tea. They stimulate our own antioxidant enzymatic defenses to go into action, protecting us from the oxidative stress that our own bodies constantly produce. Supplements are another avenue of self-defense. There are any number of them that boost levels of nutrients involved in the mitochondrial production of energy. Besides the B vitamins, there’s Co Q10, ALA, Acetyl L-carnitine, Urolithin, NAD+ precursors, magnesium, omega-3 fatty acids, and that’s only a partial list. An integrative health care provider can help you develop a smart supplement strategy. 

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Melatonin is trickier. Some foods contain small amounts, for instance, walnuts, tomatoes and rice, and tart cherry juice, in particular, has been shown to modestly increase body melatonin levels and sleep times. (It’s also packed with sugar so I don’t advise going overboard.) 

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One can also go the melatonin supplement route. At doses usually in the 3-5 milligram range, it is for some an effective sleep aid, especially when used intermittently to deal with disrupted sleep patterns, for instance, caused by jet lag. When you’re older though, say once you’re over 50, your melatonin levels have dropped, your body’s simply not making much melatonin anymore, so with supplementation, in effect, you’re replacing it, or filling in the gap. For example, as an antioxidant and doe mitochondrial support I take about 10 mgs a night, but some people may need to go up to 20mg a night, while others are good with just 5 mg. You may fall somewhere in between. How much is too much? If a higher dose makes you drowsy in am or gives you nightmares, cut back on the dose.  

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Melatonin supplementation exclusively for brain health is still a work in progress; we still don’t know for sure that melatonin, orally consumed, behaves the same way as the molecule the body itself produces. But the potential is tantalizing. One review article pooled some 22 randomized controlled trials and found evidence to support the hypothesis that supplementation could improve cognitive performance in people with early-stage Alzheimer’s. 

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Safe to say the research is early days, especially when it comes to dosing which is all over the map, and there are concerns that the higher doses of melatonin investigated in these studies could cause early-morning grogginess or suppression of the body’s own melatonin production. I recommend working with an integrative health-care practitioner if you’re interested in exploring this approach.