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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

In this four-part series on what scientists call “the hallmarks of aging,” the specific biochemical processes that are happening in your body every day, every second, which, taken together, take us from our physical peak in our twenties right on through to the end of our lives.

The idea, as I explained, is “know your enemy,” as in, if we can identify what’s going on in the body, we can take steps to fight back against it, whether that’s healthy lifestyle choices now or, down the line, with the help of new treatments being studied in the lab today. Thus far, we’ve looked at the first six hallmarks of aging – genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing and mitochondrial dysfunction. In this post, we’ll take a look at the next three hallmarks of aging, cellular senescence, stem cell exhaustion and altered intercellular communication – and what you need to know them:

7. Cellular senescence — or, when cells hang on too long

Certain kinds of cells in our body are designed to continually replenish themselves by dividing, for instance, the cells in the skin, the gut, the blood, the immune system. When they come to the end of their ability to divide, they die and clear out, making way for new ones. But some of these old cells don’t get the memo and they just hang around, becoming “senescent.” This process is likely a ”downstream” effect, set in motion by some of the hallmark processes that take place inside the cell nucleus that I discussed in the previous post, like mutations to the DNA or running out of the telomeres which make cell division possible. When we’re young, some of these senescent cells may perform a valuable function, preventing cells from turning cancerous. But as we age, they become more numerous and more likely to outstay their welcome. They become malingerers, so-called “zombie cells,” interfering with tissue repair, driving inflammation and generally helping to invite the physical changes that are the downside of growing old. But researchers have in recent years made real progress puzzling out how to keep these cells in check or outright usher them off the stage.

Supplements like quercetin, fisetin, spermidine, luteolin, apigenin and piperlongumine look to have anti-senescent (or “senolytic”) effects, as do certain pharma drugs like metformin. (In one study, researchers extended the lifespan of mice by a third, by combining quercetin with a chemotherapy drug, Dasatinib.) But simply eating smartly can help put the “zombies” in their place. Apples and grapes (containing the compound quercetin), carrots and broccoli (luteolin) and turmeric (curcumin) are just some of your potential nutritional allies. We also have good evidence that exercise, especially strength-building exercise, can help put the zombies in their place.

8. Stem cell exhaustion — it’s not easy being a stem cell!

The aging body is something like an old car. It can keep running for a long time as long as we can keep replacing old, worn-out parts with new ones. That’s the job of our stem cells. Now, I have described how cells can divide, doubling their number, with the help of the telomeres which protect the ends of our chromosomes during cell division. But it’s not quite that simple. Our “differentiated” cells – say, a liver cell or a bone marrow cell or a gut cell – can’t pull off this doubling trick by themselves. They require the services of a partner, a corresponding adult stem cell which can divide, creating new copies of that particular type of cell. (Adult stem cells are distinct from embryonic stem cells formed in the first days after conception, which can and do form all the different types of cells that the body will eventually need.) And, by now this won’t surprise you, our bodies’ capacity to create new stem cells to regenerate or replace damaged tissues declines with age. We pay a price for that.

Over time, we become more and more susceptible to neurodegenerative diseases, infections that slip through a weaker immune system and slower tissue healing after injury. Right now, there’s no therapy being tested in the lab (that I’m aware of) that might rejuvenate stem cells on such a grand scale that it could be said to slow aging. Instead, we have clinical trials and for-profit clinics (mostly outside the FDA’s purview) which are injecting adult stem cells, derived from bone marrow or fat, that target particular problem areas, joint pain and deterioration being the most common. (We’ve also had full-on bone-marrow transplants as a last-line therapy for blood cancers for some decades now.) But when it comes to rejuvenation, your body’s own ability to generate stem cells across the board, it’s back to the lifestyle basics and the usual supplement/pharma suspects like curcumin, vit D3, vit C, fish oil, and metformin that you may want to explore with an integrative physician. Colostrum, resveratrol and seabuck thorn berry extract look interesting, but the jury is still out on them. Some pro-active folks are availing themselves of companies that bank their frozen adult stem cells – the younger you do it, the younger the stem cells, the more potent they should be – saving them for that rainy day when they need that “spare part” and, hopefully, the regeneration technology is that much more advanced.

9. Altered intercellular communication — or, when your cells’ reception gets patchy

A lot of what makes human life possible is different kinds of cells talking to each other. Maybe it’s neurons in the brain sending signals to muscle cells to move the body in a certain way. Or it could be hormones secreted by your pancreas, directing glucose to be burned for energy, or from your adrenals putting your entire system on high alert.

Our bodies couldn’t manage the complex business of staying alive without countless numbers of these inter-cellular conversations happening every second. And, as you’ve probably guessed by now, over time, the cells’ reception gets spottier. Any number of the “hallmarks of aging” can be contributing to this degradation but researchers think inflammation (more on that in a moment) is particularly important. Not only does chronic inflammation get in the way of efficient cellular communication, but this impaired cell talk drives further inflammation. Important conversations drop out or become garbled, helping to accelerate the aging process across the board and driving up the risk of cancer and dementia, in particular. What can we do about it? A good bit. The omega 3 fats in oily fish (salmon, herring, anchovies) and nuts and seeds make the best building material for the cell walls, helping to keep them supple and fluid, allowing information to pass between cells more easily. Managing stress so that it doesn’t become chronic, so you’re not pickling your cells in stress hormones, is important. And, here once again, the research backs up the positive effect of physical activity, especially in the more sustained form that we call exercise.

So where do we go from here? What comes after cellular senesce, stem cell exhaustion and altered intercellular communication? See my post next week when I cover the final three hallmarks of aging, including: compromised autophagy, microbiome dysbiosis and inflammation.

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