Category: Aging

New Longevity Drugs for Dogs Can Be Proof-of-Concept for Longevity Drugs for People

(p. A1) “When you adopt a dog, you’re adopting future heartbreak,” said Emilie Adams, a New Yorker who owns three Rhodesian Ridgebacks. “It’s worth it over time because you just have so much love between now and when they go. But their life spans are shorter than ours.”

In recent years, scientists have been chasing after drugs that might stave off this heartbreak by extending the lives of our canine companions. On Tuesday, the biotech company Loyal announced that it had moved one step closer to bringing one such drug to market. “The data you provided are sufficient to show that there is a reasonable expectation of effectiveness,” an official at the U.S. Food and Drug Administration informed the company in a recent letter. (Loyal provided a copy of the letter to The Times.)

That means that the drug, which Loyal declined to identify for proprietary reasons, has met one of the requirements for “expanded conditional approval,” a fast-tracked authorization for ani-(p. A19)mal drugs that fulfill unmet health needs and require difficult clinical trials. The drug is not available to pet owners yet, and the F.D.A. must still review the company’s safety and manufacturing data. But conditional approval, which Loyal hopes to receive in 2026, would allow the company to begin marketing the drug for canine life extension, even before a large clinical trial is complete.

. . .

. . . the letter, which came after years of discussion between Loyal and the F.D.A., suggests that the agency is open to canine longevity drugs, Ms. Halioua said.

. . .

Aging may be an inevitability, but it is not an unyielding one. Scientists have created longer-lived worms, flies and mice by tweaking key aging-related genes.

These findings have raised the tantalizing possibility that scientists might be able to find drugs that had the same life-extending effects in people. That remains an active area of research, but canine longevity has recently started to attract more attention, in part because dogs are good models for human aging and in part because many pet owners would love more time with their furry family members.

“There’s not a lot you wouldn’t do if you could stack the deck in your favor to preserve the life of your hairy, four-legged child,” said Ms. Adams, the Rhodesian Ridgeback owner.

For the full story, see:

Emily Anthes. “A Drug Aims to Extend Dogs’ Lives, Yes It Does.” The New York Times (Saturday, November 29, 2023): A1 & A19.

(Note: ellipses, and bracketed year, added.)

(Note: the online version of the story was updated Nov. 29, 2023, and has the title “Could a Drug Give Your Pet More Dog Years?”)

Alleged Upper Bounds to Lifespans Continue to Be Surpassed

(p. A2) In a 2002 paper, “Broken Limits to Life Expectancy” the demographers Jim Oeppen and James Vaupel showed that for nearly 100 years, estimates of when life expectancy would hit its limit were proven wrong, often in just a few years. In 2020, Max Roser of the University of Oxford noted that this trend was still intact.

There is no guarantee, of course, that this trend will continue over time or everywhere. Perhaps pandemics, weather disasters or fentanyl deaths will become widespread enough to outweigh improvements in cancer treatment and so on. But I wouldn’t bet on it.

The better bet, according to demographers, is that children born this year will live longer than children born in any previous year.

For the full commentary, see:

Josh Zumbrun. “THE NUMBERS; The Good News About Life Expectancy.” The Wall Street Journal (Saturday, December 16, 2023): A2.

(Note: the online version of the commentary has the date December 15, 2023, and has the title “THE NUMBERS; The (Surprisingly) Good News on Life Expectancy: It’s Still Going Up.”)

The Oeppen and Vaupel article mentioned above is:

Oeppen, Jim, and James W. Vaupel. “Broken Limits to Life Expectancy.” Science 296, no. 5570 (May 10, 2002): 1029-31.

The 2020 article by Roser, updating the Oeppen and Vaupel paper, is:

Roser, Max. “The Rise of Maximum Life Expectancy: Predictions of a Maximum Limit of Life Expectancy Have Been Broken Again and Again.” Last updated March 1, 2020 [cited Sat., Dec. 16, 2023]. Available from https://ourworldindata.org/the-rise-of-maximum-life-expectancy.

Many Long-Lived Ashkenazi Jews Did NOT Follow Usual Advice on Exercise, Diet, Sleep, and Social Connectivity

(p. B10) Louise Levy, who along with hundreds of others 95 and older was part of a study to understand how their genetic makeup led to their good physical and cognitive health during extremely long lives, died on July 17 [2023] in Greenwich, Conn. She was 112.

. . .

Mrs. Levy was one of more than 700 people, all 95 or older, recruited since 1998 to participate in a study by the Institute for Aging Research at the Albert Einstein School of Medicine in the Bronx to learn the genetic reasons for their unusually long, healthy lives.

“It’s not luck,” Dr. Nir Barzilai, an endocrinologist who directs the institute, said by phone. “They exceeded luck. The biggest answer is genetics.”

Using the blood and plasma of the test group, all Ashkenazi Jews — a comparatively homogeneous population whose genetic variations are easier to spot — the institute’s Longevity Genes Project has discovered gene mutations that are believed to be responsible for slowing the impact of aging on people like Mrs. Levy and protecting them against high cholesterol, heart disease, diabetes and Alzheimer’s disease.

“The most striking thing about them is they had a contraction of morbidity,” Dr. Barzilai said. “They are sick, as a group, for very little time at the end of their lives.”

He added, “Did they do what we know we should do — exercise, diet and sleep and have social connectivity? The answer is mostly no. Sixty percent were smoking. Less than 50 percent did much household activity or biking. Fifty percent were overweight or obese. Less than three percent were vegetarians. So they weren’t special in that sense.”

The goal of the research is the development of drugs that would imitate what the centenarians’ genes do to protect their health.

For the full obituary, see:

Richard Sandomir. “Louise Levy, 112, Longtime Subject in a Genetic Study of Human Longevity.” The New York Times (Saturday, July 29, 2023): B10.

(Note: ellipsis, and bracketed year, added.)

(Note: the online version of the obituary was updated July 31, 2023, and has the title “Louise Levy, Who Was Studied for Her Very Long Life, Is Dead at 112.”)

“If You Work Forever, You Can Live Forever”

(p. B12) At age 80, Byron Wien compiled “20 Life Lessons” from a long career as a Wall Street soothsayer. “Never retire” was No. 20. “If you work forever, you can live forever,’’ he explained. “I know there is an abundance of biological evidence against this theory, but I’m going with it anyway.”

Mr. Wien (pronounced ween) didn’t outrun biology. But when he died on Oct. 25 [2023], at 90, he was still engrossed daily in reading the economic tea leaves for his most recent employer, the private equity firm Blackstone. He continued to call politicians, central bankers and financial titans around the world for intelligence to help shape his strategic reports for his firm. And if he felt that his own colleagues weren’t picking his brain enough or adding him to enough meetings, he would tell them he had plenty of bandwidth.

“He was thirsty for knowledge and probably the most curious individual I have ever come across,” said Joan Solotar, the global head of the private wealth division at Blackstone, who was Mr. Wien’s boss.

“I had the pleasure of giving Byron his annual review,” she added, in an interview, “and he would sit down and every year ask the same question: ‘Tell me what I can do better.’”

For the full obituary, see:

Trip Gabriel. “Byron Wien, 90, Wall Street Seer of the Unexpected.” The New York Times (Saturday, November 11, 2023): B12.

(Note: bracketed year added.)

(Note: the online version of the obituary has the date Nov. 9, 2023, and has the title “Byron Wien, Wall Street Seer of the Unexpected, Dies at 90.”)

“Flowers Never Bend, With the Rainfall”

Sometimes when I am in a dark mood I wonder how you keep moving forward when you do not know how much time is left. Some seek an answer in religion. I am more open to a kind of stoicism combined with the other gift of Prometheus: blind hope.

(p. 3) A few months into treatment, I realized that Josh might not make it to the next spring, when we would normally visit my extended family in Greece. I told Dr. Sara that I would like to take my husband to Greece, because he might not get the chance again.

. . .

My diary reminds me that while we were there, I asked Josh what he would do differently in life. “Not get cancer,” he said.

. . .

As for me, I kept hearing the lyrics to a Simon and Garfunkel song in my head: “So, I’ll continue to continue to pretend, my life will never end, and flowers never bend, with the rainfall.” It was my soundtrack.

For the full commentary, see:

Anemona Hartocollis. “My Husband’s Doctor, Onscreen.” The New York Times, SundayStyles Section (Sunday, November 20, 2022): 1-3.

(Note: the online version of the commentary was updated June 20, 2023 [sic], and has the title “Cancer, My Husband’s Doctor, and Catherine Deneuve.”)

Okinawans Think Ikigai (a Reason for Living) Is Important for Long Life

(p. A11) Ask most people if they want to live to be 100 and the response is likely to be “Sure!” followed by “Wait a sec . . .” Questions suddenly abound: Am I going to be healthy? Am I going to be lonely? Will I be financially stable? Will I have outlived everyone I knew and loved? What author-researcher Dan Buettner set out to demonstrate in “Live to 100: Secrets of the Blue Zones” is that the solutions to those concerns are also the keys to longevity itself.

. . .

What is clear early on is that what Mr. Buettner “discovers” during his visits to Sardinia; Singapore; Okinawa, Japan; Ikaria, Greece; and even Loma Linda, Calif., is largely what we would expect: that much of what helps people live longer isn’t necessarily the purple Japanese sweet potatoes, or going to church every day, or having the limited stress load of a Greek shepherd. It is an Okinawan diet rich in nutrients and fiber, the walking uphill to the Sardinian church, and the community to which one belongs in Loma Linda when one is, for instance, a Seventh Day Adventist who plays pickleball.

. . .

There are many correlating clues to a longer life across the locations in “Live to 100.” Okinawans emphasize the importance of having an ikigai, or reason for living; in Costa Rica the same thing is called one’s plan de vida.

For the full television review, see:

John Anderson. “Netflix’s Lessons in Longevity.” The Wall Street Journal (Wednesday, Aug. 30, 2023): A11.

(Note: ellipses added.)

(Note: the online version of the television review has the date August 29, 2023, and has the title “‘Live to 100: Secrets of the Blue Zones’ Review: Lessons in Longevity.” In the original the word ikigai and the phrase plan de vida are in italics.)

Buettner’s latest book on blue zones is:

Buettner, Dan. The Blue Zones Secrets for Living Longer: Lessons from the Healthiest Places on Earth. Washington, D.C.: National Geographic, 2023.

Michael Milken Applies “Entrepreneurial Zeal” to Quest to Live Forever

(p. B3) Michael Milken wants to live forever.

. . .

Milken in April [2023] published “Faster Cures,” a book that is part memoir, part a recounting of his efforts to bring the results of medical research to patients more quickly.

. . .

Shortly after his release from prison in 1993, he received a diagnosis of terminal prostate cancer and was told he had 12 to 18 months to live. He survived thanks to a relentless pursuit of the latest treatments and a dramatic change in diet. Longevity is one focus of the Milken Institute.

. . .

While at Berkeley, Milken read a book called “Corporate Bond Quality and Investor Experience” that examined, among other things, yield charts and default rates for bonds issued by railroads, utilities and industrial companies between 1900 and 1943.

The data revealed something surprising, he recounted in “Faster Cures:” While risk and return had always been presumed to be directly correlated, the reality was that the market had historically overestimated the risk of higher-yielding investments. Investors actually got lower returns on a portfolio of high-grade bonds than they did on a portfolio of low-grade ones over time because the higher yields more than made up for the higher level of defaults.

Milken continued his work on high-yield bonds while pursuing an M.B.A. from the University of Pennsylvania’s Wharton School. When he graduated in 1970, he joined the staff of Drexel, where he had previously worked as a consultant.

Bonds issued by Drexel were the primary source of financing for the likes of cable-industry titan Ted Turner, cellular pioneer Craig McCaw, fiber-optic entrepreneur William McGowan and casino magnate Steve Wynn.

“There was an entrepreneurial zeal in that firm that I haven’t seen since,” said Ted Virtue, a Drexel alumnus who now runs private-equity firm MidOcean Partners.

. . .

Milken’s work on prostate cancer has also made him an influential figure in medical research, where he has developed a reputation for being data-driven and impatient with bureaucracy. Every year he hosts a summit for scientists working on prostate cancer.

“Mike looked at the problem of cancer like a business problem to be solved,” said Dr. Karen Knudsen, CEO of the American Cancer Society. “He wasn’t focused on the flashy. He really focused on what is going to make a difference.”

When the Prostate Cancer Foundation lacked the resources to fund a major study Knudsen needed to conduct to advance her research, she said, Milken introduced her to executives from a pharmaceutical company who he thought would be interested in the science. The company ended up funding the study.

For the full story, see:

Miriam Gottfried. “Bond King, Felon, Billionaire Philanthropist.” The Wall Street Journal (Saturday, July 15, 2023): B3.

(Note: ellipses, and bracketed year, added.)

(Note: the online version of the story was updated July 14, 2023, and has the title “Bond King, Felon, Billionaire Philanthropist: The Nine Lives of Michael Milken.”)

Milken’s book on how to cure more diseases faster is:

Milken, Michael. Faster Cures: Accelerating the Future of Health. New York: William Morrow, 2023.

Psychedelics May Return Brains to More “Plastic” Adaptable Form

(p. C4) New studies suggest that psychedelics, carefully administered in controlled settings with trained therapists, can help treat mental illnesses like depression, addiction and PTSD. But just how do psychedelics achieve these therapeutic effects?

A new study in the journal Nature by the neuroscientist Gul Dolen at Johns Hopkins and colleagues tackles this question.

. . .

. . ., Dolen’s team gave mice a variety of psychedelics and observed their effects. Mice, like people, have what are called “critical periods” for various kinds of development—times when the brain is especially open to new experiences and especially likely to learn and change. After a critical period closes, that type of learning is much harder. These specific critical periods reflect a more general phenomenon: Brains start out more “plastic,” easier to change and more sensitive to experience, and get more efficient but more rigid as people—or mice—grow older.

. . .

As expected, the different drugs acted through different chemical mechanisms. But all of them ultimately activated genes that made the brain more “plastic,” more easily changed.

Other research shows that psychedelics may reopen other kinds of critical periods. For example, amblyopia, or “lazy eye,” must be treated early for the visual cortex to rewire properly. But a 2020 study published in Current Biology found that ketamine reopened the visual critical period in mice, allowing older animals to recover from amblyopia.

These results have important implications for psychedelic therapy. We know that the effects of psychedelics depend on “set and setting”—the context and the attitude of the person who takes them—and that psychedelic experiences can feel wonderful or terrible to the user. The new research suggests that psychedelics work by opening up the brain to new possibilities, allowing it to escape from old ruts, change and learn. That might give humans a chance to change addictive habits or destructive thought patterns.

For the full commentary, see:

Alison Gopnik. “MIND & MATTER; The New Promise of Psychedelics.” The Wall Street Journal (Saturday, July 22, 2023): C4.

(Note: ellipses added.)

(Note: the online version of the commentary has the date July 20, 2023, and has the same title as the print version.)

The academic article discussed in the passages above is:

Nardou, Romain, Edward Sawyer, Young Jun Song, Makenzie Wilkinson, Yasmin Padovan-Hernandez, Júnia Lara de Deus, Noelle Wright, Carine Lama, Sehr Faltin, Loyal A. Goff, Genevieve L. Stein-O’Brien, and Gül Dölen. “Psychedelics Reopen the Social Reward Learning Critical Period.” Nature 618, no. 7966 (June 14, 2023): 790-98.

“Best-Funded Startup” in History Seeks Longevity by Rejuvenating Cells

(p. B1) Arch is the largest institutional investor in Altos, which already has $3 billion of committed investments, likely making it the biotech indus-(p. B2)try’s best-funded startup on record.

Nelsen is characteristically unrestrained when discussing Altos’s prospects.

“Epigenetic reprogramming is the biggest thing in healthcare in 100 years. Or ever,” he says. “We will clearly live much healthier and longer lives if this works.”

. . .

A native of Walla Walla, Wa., Nelsen studied biology and economics at the University of Puget Sound before getting an M.B.A. at the University of Chicago.

. . .

His manic energy can lead to confrontations. Nelsen drives his GMC Yukon so aggressively that some friends avoid riding with him. He’s started fights with supermarket customers who resisted using plastic bags.

“I hate plastic bag bans, because the assumption that they are better for the environment than paper is flawed and I am grown up enough to not have government choose my bag for me,” Nelsen says.

. . .

Taking cells back to their youthful, healthier state long captured the imagination of scientists, but seemed unlikely. Then a breakthrough paper published in 2006 by Japanese scientist Shinya Yamanaka and a colleague showed mature skin cells of mice could be reprogrammed into primordial, immature stem cells—called induced pluripotent stem cells—in effect resetting their molecular clocks. Yamanaka, who later shared a Nobel Prize for work in this area, is an adviser to Altos. In 2016, Spanish biochemist Juan Carlos Izpisua Belmonte, Altos’s founding scientist, showed how the age of cells could be reverted without changing their genome and identity. His work demonstrated the potential for toggling between the ‘old’ and ‘young’ states of cells—the basis for Altos’s effort to rejuvenate cells.

For the full story, see:

Gregory Zuckerman. “Fear of Death Drives A Venture Capitalist.” The Wall Street Journal (Monday, Aug. 21, 2023): B1-B2.

(Note: the online version of the story has the date August 20, 2023, and has the title “For This Venture Capitalist, Research on Aging Is Personal; ‘Bob Has a Big Fear of Death’.”)

With Repetitions Surgeons Gain Informal Knowledge, Such as “Muscle Memory”

(p. C6) Imagine you’ve been admitted to the hospital and you’re meeting the physician taking care of you for the first time. Who are you hoping walks through that door? Would you rather they be in their 50s with a good amount of gray hair, or in their 30s, just a few years out of residency?

In a study published in 2017, one of us (Dr. Jena) and colleagues set out to shed some light on the role of age when it came to internists who treat patients in hospitals. These physicians, called hospitalists, provide the majority of care for elderly patients hospitalized in the U.S. with some of the most common acute illnesses, such as serious infections, organ failure and cardiac problems.

. . .

. . ., the results suggested if the over-60 doctors took care of 1,000 patients, 13 patients who died in their care would have survived had they been cared for by the under-40 doctors. We repeated the analysis using 60- and 90-day mortality rates, in case longer term outcomes might have been different, but again, the pattern persisted: Younger doctors had better outcomes than their more experienced peers.

. . .

Younger doctors possess clinical knowledge that is more current. If older doctors haven’t kept up with the latest advances in research and technology, or if they aren’t following the latest guidelines, their care may not be as good as that of their younger peers.

. . .

. . ., a separate study by Dr. Jena and colleagues looked at about 900,000 Medicare patients who underwent common non-elective major surgeries (for example, emergency hip fracture repair or gall bladder surgery) performed by about 46,000 surgeons of varying age.

. . .

The results showed that unlike hospitalists, surgeons got better with age. Their patient mortality rates had modest but significant declines as they got older: mortality was 6.6% for surgeons under 40, 6.5% for surgeons age 40-49, 6.4% for surgeons age 50-59, and 6.3% for surgeons over age 60.

Clearly something different was happening here. It may be that for hospitalists, the benefit of steadily increasing experience starts to be outweighed by their waning knowledge of the most up-to-date care. It’s different for surgeons, though, who hone many of their skills in the OR. Surgeons build muscle memory through repetition, working in confined spaces with complex anatomy. They learn to anticipate technical problems before they happen and plan around them based on prior experience. Over time, they build greater technical skills across a wider variety of scenarios, learn how to best avoid complications, and choose better surgical strategies.

What does this mean for all of us as patients when we meet a new doctor? Taking studies of hospitalists and surgeons together, it’s clear that a doctor’s age isn’t something that can be dismissed out of hand—age does matter—but nor can it be considered in isolation. If we’re concerned about the quality of care we’re receiving, the questions worth asking aren’t “How old are you?” or even “How many years of experience do you have?” but rather “Do you have a lot of experience caring for patients in my situation?” or “What do you do to stay current with the research?”

For the full essay, see:

Anupam B. Jena and Christopher Worsham. “Do Younger or Older Doctors Get Better Results?” The Wall Street Journal (Saturday, July 8, 2023): C6.

(Note: ellipses added.)

(Note: the online version of the essay was updated July 8, 2023, and has the same title as the print version.)

The essay quoted above is adapted from the book:

Jena, Anupam B., and Christopher M. Worsham. Random Acts of Medicine: The Hidden Forces That Sway Doctors, Impact Patients, and Shape Our Health. New York: Doubleday, 2023.

The “Deliciously Guilty Pleasure” and “Disorienting Joy” of California Skiing in August

(p. A20) This weekend, . . . hordes of Californians are smearing pink and yellow zinc oxide on noses, shoving feet into hard plastic ski boots and gliding over to the lifts at Mammoth Mountain for yet another day on the slopes. A reminder: It’s August.

. . .

Unpredictable change is the new status quo.  . . . it can also, in a rare instance like the chance to ski in the dog days of summer, bring a disorienting joy.

. . .

In mid-July [2023], well after all the hot dogs and fireworks, I headed up to the Sierra and ran into so much lingering snow that the road through Yosemite National Park hadn’t yet opened for the season. I took an alternate route, 108 over Sonora Pass, and saw people parking in turnouts, carrying skis up dirt trails through trees, stepping onto sunny snow slopes and linking turns back down to ice chests full of cold drinks before, you know, maybe going for a swim. When I finally got to Kelly’s place, the creek on her high desert property frothed in a fabulous white and clear torrent through sage lands sparkling with superblooming yellow mule’s ear, red paintbrush and white phlox. The big peaks, meanwhile — in the dead heat of a California summer — remained so heavily blanketed in snow that I felt I was seeing them the way Indigenous people must have during the Little Ice Age, 500 years ago.

The premise of California’s secular faith in nature is that water plus sunshine equals enlightenment. In high school I was transfixed by a description on the jacket of Bank Wright’s classic “Surfing California” of “skiing Mount Baldy in the morning and surfing Hermosa Beach in the afternoon.” That struck the teenage me as the absolute perfect way of snatching healthy peace and giddy fun from the predictable maw of adult misery.

. . .

. . . when I drove to Mammoth, put on my favorite cowboy hat against the sun and sipped iced coffee while watching tiny black figures ski down blinding white slopes, the experience was perhaps best likened to the queasy adrenalized thrill of an oncoming manic episode after a long and dark depression — worrisome, yes, bound for nowhere good but, as long as we’re just talking here and now, a deliciously guilty pleasure.

For the full commentary, see:

Daniel Duane. “The Upside of Climate Chaos? Skiing in August.” The New York Times (Monday, August 7, 2023): A20.

(Note: ellipses, and bracketed year, added.)

(Note: the online version of the commentary has the date Aug. 6, 2023, and has the title “It’s August. Californians Are Still Skiing. Don’t Ask.”)