Back in 1965, a 90-year-old French woman named Jeanne Calment signed a “reverse mortgage" deal with her lawyer, a guy named André-François Raffray. In exchange for ownership of her luxurious Parisian apartment, Raffray—then aged 47—agreed to pay Mme Calment 2,500 francs a month and let her live there until she died. It sounded like he’d made a good bet, but unfortunately for the lawyer, he didn’t know that he'd signed a contract with the woman who would go on to become the oldest recorded person in history. She would outlive her only child and her only grandchild, and despite being twice Raffray’s age when they made their deal, Jeanne incredibly outlived him too. The lawyer passed away in 1995 at age 77, by which time he'd paid Jeanne more than double the apartment’s value—turned out not to be such a good bet after all. Her date of birth was preserved with her original birth certificate and her age was documented in over 25 census surveys. She was born in Arles, France, on February 21, 1875 (14 years before the Eiffel Tower was built) and lived on to become the oldest person ever verified, reaching the age of 122 years and 164 days when she passed away on August 4, 1997. We’ve talked before in these posts about keys to healthy aging but reaching 122 is an entirely different matter. These folks are called “superagers,” and it takes a whole lot of good luck, good genes, and good habits to get there.
Beyond the headlines and pop culture promises of eternal youth, true advances in organ transplants, epigenetic clocks, and cellular reprogramming are redefining aging to help people live longer and stay healthier as the years pile up. Some Silicon Valley billionaires publicly
declare they are going to use all kinds of technology and don’t plan to die—we’ll see. It’s even gotten into the heads of some world leaders. A little while back an open microphone picked up Russian President Vladimir Putin and Chinese President Xi Jinping talking about biotechnology and organ transplants and their goal of living to 150 years or even achieving immortality—and probably planning to stay in power until then. All the medical literature on superagers stresses that adding years is not enough; preserving quality of life is crucial. This has given rise to the concept of “healthspan” added to models of lifespan. The main focus of healthspan is not just getting old—really old like into the triple digits—but all the time maintaining your cognitive and intellectual well-being. So, the key to super aging is all in our heads, literally; it’s brain health. We've talked in these pages about healthy habits to help preserve cognitive health, and modern medicine is all over this too.
“Geroprotective” (protecting against the negative effects of aging) drugs are among the most immediately promising treatments to help us slow down the biological aging process and are designed to target molecular pathways common to many age-related diseases. We’ve already talked in these pages about GLP-1s (now available in oral pill forms), and researchers have shown this class of meds has some age-protective effects. Most current research focuses on metformin, rapamycin, and senolytics. Senolytics are a whole new class of meds that are designed to clean up aging cells and promote new cell growth—cellular regeneration. Since the key to healthspan is youthful cognition and intellect as we age, it’s most important for that regeneration to occur in brain cells, since it’s cell loss in our heads that portends cognitive decline and senility. Until very recently, no neuroscientists thought that such a thing as brain cell regeneration existed, but new research has brought some good news and it correlates with just this issue of brain cell regrowth and maintaining cognitive function.
There’s an area of the brain called the hippocampus and it’s vital to our intellectual function. The hippocampus is a seahorse-shaped structure within the brain’s temporal lobe that plays a vital role in forming memories, spatial navigation, social interactions, and emotional processing. The name is appropriate and comes from the Greek words for “sea monster,” reflecting its distinctive curved shape that looks like a mad seahorse. It’s not a storage vault for memories; rather, it acts more like a processing area, a temporary workshop, where new experiences are processed and prepared for long-term storage in other parts of the brain, the cortex. Without the hippocampus to perform this initial encoding, the transfer and memory storage can't happen. That's why people with hippocampal damage can remember details of their childhood but can’t remember where they put their glasses half an hour ago, a common symptom of age-related senility and Alzheimer’s disease.
A study published last month in Nature shed some fascinating insights into the difference between the brains of “super healthspanners” (don’t look it up, I just invented that word cocktail) with intact cognitive function and patients with this kind of age-related Alzheimer’s disease (AD) and senility. The brains of superagers, defined as octogenarians with a memory capacity equal to or better than that of younger adults, contain more than twice as many new neurons as those of typical older adults and 2.5 times as many as those with age-related cognitive decline. This finding is based on cell profiles of 355,997 samples, so it’s pretty statistically meaningful. According to the most interesting part of the research, it turns out it’s in the most very critical area that the difference in cell content was due to cell regrowth—the “super-healthspanners” actually have regeneration of aging nerve cells in the hippocampus, thus preventing AD and senility. This is the first time nerve cell regrowth has been seen in the brain!
The obvious question is whether a truly world-class discovery like this can be put to clinical use. I’ve talked about stem cells in past articles and their critical role in organ rejuvenation. Is it possible there’s some way of juicing along stem cells in the hippocampus of AD patients to enhance regeneration of these critical cells? In 2006, Shinya Yamanaka, a stem-cell biologist then at Kyoto University in Japan, discovered four proteins that aided in cell duplication that he called “transcription factors,” which later came to be known as “Yamanaka Factors.” More recently investigators at MIT in Boston found that these factors could transform and reprogram adult cells into a kind of special stem cell known as “pluripotent stem cells” that are capable of taking on new identities in many parts of the body. This paves the way to stem cell–based therapies where specializer cells are coaxed into adopting a certain function and then injected into a patient, replacing worn-out cells in critical areas that are damaged or aging. Combining this with the findings that brain cells can regenerate would be a huge step forward. Just this February, regulators in Japan approved the first such cell-based therapies for severe heart failure and nerve degeneration in Parkinson’s disease. In other words, stem cells can be “reprogrammed“ to replace damaged dopamine-producing brain cells. That sets up the next step—finding ways to stimulate those cells in the hippocampus to regenerate. It’s a bit off in the future yet, but the research is pointing to some attainable ways to use science to do what Jeanne Calmet accomplished naturally and what Putin and Xi Jinping want to engineer for themselves, immortality. At least it’s an attainable way to ease the burden for patients with Alzheimer’s disease and elderly patients with senility.
So, hang in there—do all the things we’ve talked about to live healthy lives and take comfort that more help is on the way. As always—Fly Safe—otherwise, all the future treatments will be for naught.
