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 Dr. Frank Lipman sits on a chair, cross-legged, arm resting on the back of the chair, lightly touching his other hand that is resting on his thigh. He is wearing blue denim, a blue dress shirt and a navy textured blazer and black glasses. He is smiling, showing his front teeth looking off to the side.

Dr. Frank Lipman

Chief Medical Officer at THE WELL

Updated: 04/04/2024

With this, my fourth in a series of posts devoted to the “hallmarks of aging,” now it’s time to head to the current front lines of anti-aging science, completing the list of the processes inside the body that we think are responsible for the making us grow old – and hopefully not before our time, if we follow some sensible lifestyle advice.

While the nine hallmarks that were advanced back in 2013, these final three hallmarks have been added only recently. They had been folded into the pre-existing hallmarks, not surprising since all the hallmarks affect each other, one way or another. But now they’ve got their own spot on the marquee. I say, it’s high time. “Compromised autophagy,” “microbiome dysbiosis” and “inflammation” are especially sensitive to the daily choices we make about diet, physical activity and stress, all topics that I’ve been discussing with my patients and my readers for some time. But whether or not your new to these ideas, in brief, here’s why they matter – and what you need to know about the final group of hallmarks:

10. Compromised autophagy — or, when the trash doesn’t get picked up

When the trash doesn’t get picked up in front of your house or apartment, it can be an unsightly nuisance. Inside your cells, it’s more serious than that. Over the past decade or so, researchers figured out that the recycling of old, damaged cell parts (in the cell’s recycling center, the lysosome) is an essential way that cells maintained their own life and, by extension, the life of the organism, or, in this case, you. And as you get older, and your cells get less vigilant about tending to the recycling, bad things happen. Sometimes, the junk parts build up, getting in the way of the business of the cell; sometimes the cells just die before they otherwise would have needed to. We know now that this “compromised autophagy” helps drive some of the other “hallmarks” that I’ve already covered, including DNA damage, impaired nutrient sensing, and protein production/destruction balance. Consequently, it’s now seen as a co-conspirator behind some of the worst diseases of aging, like cancer and neurological and immune system decline.

Fortunately, we have some interesting preliminary evidence indicating that we can enhance autophagy and slow down aging. In one study, researchers did just that with lab rats and increased their lifespans. Closer to home, this time a study with human seniors, the volunteers saw a more robust immune response to a vaccine after receiving an autophagy boost by supplementing with spermidine, a natural compound found in the body and in a wide variety of foods. You may want to look into supplementation with an integrative practitioner. But know that a whole range of healthy stressors (known collectively as “hormesis”), from intermittent fasting to short intense bursts of exercise, look to give your cellular trash-collectors a push in the right direction.

11. Microbiome dysbiosis — or, when your gut bacteria takes a wrong turn

This one is especially close to my heart. While traditional medical systems like Ayurveda from India have always emphasized the importance of the gut in overall human health, modern Western medicine tended to give it the short shrift, that is unless it was dealing with severe inflammatory conditions like colitis. But I, and other, integrative practitioners picked up on newer microbiology research a while ago and for years now have been stressing the key role played by the gut microbiome in maintaining body and mind well-being.

In short, the bacteria that reside in the gut protect the gut lining so that bad actors don’t escape into the bloodstream and they ally with the gut’s own immune system to ward off toxic intruders coming down the pike, as well as helping it not to overreact to non-toxic arrivals like the gluten proteins found in most grains.

When the communities of bacteria in the gut are not in balance – in simplest terms, too few of the good, too many of the bad – inflammation is the result. This “dysbiosis” can show up in a wide range of symptoms, both inside and outside the gut, everything from irritable bowel syndrome (IBS) to skin rashes to depression, brain fog or fatigue.

Over the past few years, researchers have integrated aging into this gut microbiome picture. Like the rest of our parts and systems, the microbiome changes as we enter our senior years. New studies are beginning to identify different gut microbial patterns in older folks that predict both longer and shorter lifespans. There’s still a lot that needs to be parsed out here. But we know enough to say that the better you protect your gut now – think, a high-fiber, whole food diet – the better your gut microbiome will age, just like the rest of you.

12. Inflammation — where (almost) all aging roads lead

As you’ve probably picked up now, most, if not all, of the hallmarks of aging contribute to inflammation. In fact, it was so integrated into the story of our physiological decline that it didn’t merit its own spot on the original list of nine. Now, leading researchers have corrected the omission and given it its own place of dishonor. But let’s be clear. Inflammation has its good side; none of us would ever survive childhood without it. It is our immune system’s first response to injury or infection, sending out a bunch of different cells to cordon off the affected area, setting the stage, if necessary, for the next wave of immune cells, antibodies that target a specific microbial enemy.

But, upside of our inflammatory response begins to run out of gas as we push beyond middle age. It stays turned on for no good reason, and at only partial strength, running down the batteries, so it can’t mount a strong response when a real invader does come along. We call that chronic inflammation. It’s a major driver behind most common diseases of aging like cancer, heart disease and diabetes, to such a degree that some researchers now use the term inflamm-aging to describe the process. And if we’re fortunate enough to elude those diseases in our senior years, chronic inflammation explains how it comes to pass that a formerly non-lethal infection like pneumonia might carry us off in our late 80s or 90s. But the more we can build up what some call our “reserve capacity” before we hit old age – healthy diet, moving the body and not letting stress get the upper hand – the longer and more happily we can postpone that fate.

As it is often said, aging begins at birth. And while we may at times worry that we’re destined to age poorly because of how our relatives did, thinking the family ‘bad genes’ are our destiny, they’re really only part of the story. It’s important to remember that our lifestyle choices, good or bad, can have a tremendous impact on our aging, so keep in mind that how well age is, in many ways, up to us. In other words, even if you made less-than-stellar choices in the past, it’s never too late to start aging well, so the improvements begin!

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