By now, you probably know I have a deep and abiding curiosity about all things related to longevity and healthy aging. And honestly, how could I not? There’s so much new, exciting research, with discoveries popping up almost every day, we’re fortunate indeed to be living in such scientifically fruitful times. These discoveries generate fresh insights about how we can age better—with more vitality than older generations had access to. 

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Of course, the essentials still matter—a lot. Eating well, staying active, managing stress, getting good sleep, these will always be the foundation for a long, vibrant life. But behind the scenes in the lab, scientists are getting better and better at understanding the biological processes that drive aging: how our cells wear down, why inflammation becomes chronic, and what leads to the slow-but-steady decline we think of as “getting old.”

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But, now that we know so much about the biology of aging, and the 12 major markers of aging, can we actually treat it? Can we slow it down, or even reverse some of aging’s effects? The answer is getting closer every day. In fact, in a few cases, we may already have some powerful tools at hand. But only now are we beginning to understand how best to use them. So, which ones may be the game changers when it comes to living better for longer? Here’s a topline on the most promising ‘big three’ tools currently in our longevity toolbox:

The Big Three have one odd thing in common: diabetes.

When we think of meds with potentially life-lengthening benefits, the dreaded rapid-ager disease of diabetes probably isn’t the first thing that comes to mind. But metformin and newer meds like the GLP-1 agonists and SGLT2 inhibitors do share a common purpose, which is to manage blood sugar levels (due to either a patient’s insufficient insulin production or resistance to insulin). While certainly helpful for those with diabetes, these meds also seem have a positive impact on mitochondrial function and energy production, which is essential for healthy aging. As mitochondrial function tends to decline as we age (along with our energy), the idea is that these meds may have potential uses in mitigating the aging process – an unexpected bonus.

The original anti-ager in millions of medicine cabinets: Metformin.

Let’s start with one the oldest, and one of the most intriguing, examples: a humble little drug called metformin, the med that’s generally well-tolerated, widely available, inexpensive and has been used safely for decades.  Originally derived from a natural compound found in a plant called goat’s rue, or French lilac, it’s been a frontline treatment for type 2 diabetes since the 1950s in Europe, and widely available in the U.S. since the mid-90s. It’s estimated that roughly 200 million or so people take it every day to help regulate their blood sugar.

Metformin’s multi-purpose magic.

Helpful as it is for blood sugar management, metformin isn’t just a diabetes drug anymore. Over the past decade, researchers have noticed something especially interesting about the stuff: people with diabetes who take metformin often live just as long—or longer—than people without diabetes. Not surprisingly, those findings got scientists wondering… could metformin be doing something to impact the aging process itself?

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It turns out, yes. Metformin seems to reduce inflammation, improve mitochondrial function, and even mimic the effects of caloric restriction — all of which are known to support longevity. What’s more, one large study found a 51% decrease in the risk of cognitive impairment, with the biggest benefit seen in patients who’d been on the drug for more than six years, indicating that metformin may be helpful for brain function to boot. 

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As studies continue, we in the longevity world are looking forward to learning even more about metformin’s ability to delay the onset of age-related disease upon the completion of the 6-year ‘Targeting Aging with Metformin Trial’ (TAME) which will study over 3,000 subjects between the ages of 65-79 at 14 research institutions.

The new(ish) kid on the block: the GLP-1 Agonists.

Metformin may be the most talked-about diabetes drug in the longevity world, but it’s far from the only one in the spotlight these days.  Next in the longevity lineup? You guessed it – the GLP-1 agonists, also known by their brand names Ozempic, Wegovy, Mounjaro, and so on. Like metformin, these drugs were also originally developed for diabetes, but they’re quickly gaining attention as potential allies in our quest for healthier, longer lives.

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About two decades ago, the first medication in a class called GLP-1 receptor agonists (short for glucagon-like peptide-1) was approved to help manage diabetes. These drugs work by mimicking a natural hormone that helps regulate blood sugar, slow digestion, reduce appetite, and stimulate insulin production. While the resulting weight loss alone can slash the risk of age-related diseases, the benefits go well beyond a trimmer waistline. In just the past few years, GLP-1 agonists have proven to be powerful tools not only for blood sugar control and weight management, but also for reducing the risk of major cardiovascular events, improving overall metabolic health, and possibly even protecting the brain by calming inflammation. There’s growing interest in their potential to treat conditions like kidney disease and sleep apnea as well. In short, the GLP-1 agonists, like metformin, may have a much broader role to play in enhancing long-term health and pushing back against aging.

Turning down the ‘noise,’ and hope for addictive behaviors.

Another incredibly exciting aspect of the GLP-1s is how these drugs affect the brain. Besides protecting brain health, anecdotal reports suggest the meds may offer a bonus for people with addictive tendencies. Studies are showing that GLP-1s can dampen compulsive pleasure-seeking behaviors and blunt users' appetites for addictive substances, such as alcohol, nicotine, cocaine or opioids. And, no surprise here, that’s a boon to over-all health and, ultimately, longevity. Here again is a potentially fruitful ‘re-purposing’ of a medication that was developed with a very different purpose in mind. 

The relative newcomer: SGLT2 inhibitors.

Last but not least, there’s another group to know about, and that’s the SGLT2 inhibitors, which arrived on the scene about a decade ago. Not as widely known as metformin and the GLP-1s, these meds – with brand names like Jardiance and Farxiga -- help the body eliminate excess glucose through the urine. They’ve been shown to protect the heart and the kidneys—two organs that can take a real beating as we get older. They improve mitochondrial function while also promoting autophagy, the cellular process that removes damaged components, further supporting cellular health. And they may also promote metabolic flexibility, that is, the body’s ability to switch back and forth between burning fats and glucose for energy. That looks to improve metabolic health by tamping down inflammation and oxidative stress, two prime drivers of aging.

What’s next – and what does all this mean for longevity?

While certain factors, like age, gender, comorbidities, and genetics can influence how individuals respond to these meds, there’s a growing sense within the scientific community that we’re on the brink of a new era in medicine—where we don’t just treat age-related diseases as they pop up, but we can start to address the root causes of aging itself. And, as always, it is essential to consult with skilled healthcare professional before considering any of these drugs for off-label use (non-diabetic use). If we haven’t quite found the fountain of youth just yet, with these three meds, plus a few more coming down the pike in the next few years, we are getting closer to the next best thing: tools that help us stay healthier for longer.