Slowing Aging Could Transform Society As We Know It
People's lives have been getting longer for more than a century. In 1900, in even the wealthiest countries, life expectancy was under 50, according to the World Health Organization. By 2015, the worldwide average was 74, and a girl born in Japan that year could expect to live to 87. Most of that extra lifespan came from improvements in nutrition and sanitation, and the development of vaccines and antibiotics.
People's lives have been getting longer for more than a century. In 1900, in even the wealthiest countries, life expectancy was under 50, according to the World Health Organization. By 2015, the worldwide average was 74, and a girl born in Japan that year could expect to live to 87. Most of that extra lifespan came from improvements in nutrition and sanitation, and the development of vaccines and antibiotics.
The question is, how will slowing aging change society?
But now scientists are trying to move beyond just eliminating the diseases that kill us to actually slowing the aging process itself. By developing new drugs to tackle the underlying mechanisms that make our bodies grow old and frail, researchers hope to give people many more years of healthy life. The question is, how will that change society?
There are several biological mechanisms that affect aging. One involves how cells react when they're damaged. Some die, but others enter a state called senescence, in which they halt their normal growth and send out signals that something's gone wrong. That signaling causes inflammation at the sight of a wound, for instance, and triggers the body's repair processes. Once everything is back to normal, the senescent cells die off and the inflammation fades. But as we age, the machinery for clearing senescent cells becomes less efficient and they begin to pile up. Some researchers think that this accumulation of senescent cells is what causes chronic inflammation, which has been implicated in conditions such as heart disease and diabetes.
The first clinical trial in humans of senolytic drugs is happening now.
In 2015, researchers at the Mayo Clinic in Minnesota and the Scripps Research Institute in Florida tested the first so-called senolytic drugs, which cause senescent cells to die. After the scientists treated mice with a combination of an anti-cancer drug and a plant pigment that can act as an antioxidant, some of the senescent cells shrank away and caused the mouse's heart function to revert to that of a much younger mouse.
"That suggests that senescence isn't just a consequence of aging, it's actually a driver of aging," says Paul Robbins, a professor of molecular medicine at Scripps and one of the researchers involved. Other animal studies have found that reducing the number of senescent cells improves a variety of age-related conditions, such as frailty, diabetes, liver disease, pulmonary fibrosis, and osteoporosis.
Now the same researchers are moving those tests to humans in the first clinical trials of senolytic drugs. In July 2016, the Mayo Clinic launched what may be the first clinical trial of senolytic therapy, studying the effect of the two drugs, called dasatinib and quercetin, on people with chronic kidney disease, which they hope to complete in 2021. Meanwhile Mayo and Scripps researchers have identified six different biochemical pathways that give rise to senescence, along with several drug candidates that target those pathways. Robbins says it's likely that different drugs will work better for different cells in the body.
Would radical life extension lead to moral deterioration, risk aversion, and an abandonment of creativity?
In Robbins' work, treating mice with senolytic drugs has extended their median lifespan—the age at which half the animals in his experiment have died—by about 30 percent, but hasn't extended the maximum lifespan. In other words, the oldest mice treated with the drugs died at the same age as mice who hadn't been treated, but more of the mice who received senolytics lived to that ripe old age. The same may turn out to be true for humans, with more people living to the limits of the lifespan—estimated by some to be about 115—but no one living much longer. On the other hand, Robbins says, it's early days for these therapies, and it may turn out that delaying aging actually does push the limit of life farther out.
Others expect more radical extensions of human life; British gerontologist Aubrey DeGray talks about people living for 1000 years, and people who call themselves transhumanists imagine replacing body parts as they wear out, or merging our minds with computers to make us essentially immortal. Brian Green, an ethicist at Santa Clara University in California, finds that concept horrifying. He fears it would make people value their own lives too highly, demoting other moral goods such as self-sacrifice or concern for the environment. "It kind of lends itself to a moral myopia," he says. "Humans work better if they have a goal beyond their own survival." And people who live for centuries might become averse to risk, because with longer lives they have more to lose if they were to accidentally die, and might be resistant to change, draining the world of creativity.
Most researchers are focused on "extending the 'healthspan,' so that the people who live into their 90s are vigorous and disease-free."
He's not too worried, though, that that's where studies such as the Mayo Clinic's are headed, and supports that sort of research. "Hopefully these things will work, and they'll help us live a little bit longer," Green says, "but the idea of radical life extension where we're going to live indefinitely longer, I think that is very unrealistic."
Most of the researchers working on combatting aging don't, in fact, talk of unlimited lifespans. Rather, they talk about extending the "healthspan," so that the people who live into their 90s are vigorous and disease-free up until nearly the end of their lives.
If scientists can lengthen life while reducing the number of years people suffer with dementia or infirmity, that could be beneficial, says Stephen Post, a professor of medicine and director of the Center for Medical Humanities, Compassionate Care, and Bioethics at Stony Brook University in New York. But even increasing the population of vigorous 90-somethings might have negative implications for society. "What would we do with all these people who are living so long?" he asks. "Would we stop having children? Would we never retire?"
Adding 2.2 healthy years to the U.S. life by delaying aging could benefit the economy by $7.1 trillion over 50 years.
If people keep working well past their 60s, that could mean there would be fewer jobs available for younger people, says Maxwell Mehlman, professor of bioethics at Case Western Reserve University's School of Law in Ohio. Mehlman says society may have to rethink age discrimination laws, which bar firing or refusing to hire people over a certain age, to make room for younger workers. On the other hand, those who choose to retire and live another two or three decades could strain pension and entitlement systems.
But a longer healthspan could reduce costs in the healthcare system, which now are driven disproportionately by older people. Jay Olshansky, an epidemiologist at the University of Illinois at Chicago School of Public Health, has estimated that adding 2.2 healthy years to the U.S. life by delaying aging would benefit the economy by $7.1 trillion over 50 years, as spending on illnesses such as cancer and heart disease drop.
For his part, Robbins says that the scientific conferences in the anti-aging field, which tend to focus on the technical research, should hold more sessions on social and economic impacts. If anti-aging therapies start extending healthy lifespans, as he and other researchers hope they will within a decade or so, society will need to adjust.
Ultimately, it's an extension of health, not just of longevity, that will benefit us. Extra decades of senescence do nobody any good. As Green says, "Nobody wants to live in a nursing home for 1000 years."
If you look back on the last century of scientific achievements, you might notice that most of the scientists we celebrate are overwhelmingly white, while scientists of color take a backseat. Since the Nobel Prize was introduced in 1901, for example, no black scientists have landed this prestigious award.
The work of black women scientists has gone unrecognized in particular. Their work uncredited and often stolen, black women have nevertheless contributed to some of the most important advancements of the last 100 years, from the polio vaccine to GPS.
Here are five black women who have changed science forever.
Dr. May Edward Chinn
Dr. May Edward Chinn practicing medicine in Harlem
George B. Davis, PhD.
Chinn was born to poor parents in New York City just before the start of the 20th century. Although she showed great promise as a pianist, playing with the legendary musician Paul Robeson throughout the 1920s, she decided to study medicine instead. Chinn, like other black doctors of the time, were barred from studying or practicing in New York hospitals. So Chinn formed a private practice and made house calls, sometimes operating in patients’ living rooms, using an ironing board as a makeshift operating table.
Chinn worked among the city’s poor, and in doing this, started to notice her patients had late-stage cancers that often had gone undetected or untreated for years. To learn more about cancer and its prevention, Chinn begged information off white doctors who were willing to share with her, and even accompanied her patients to other clinic appointments in the city, claiming to be the family physician. Chinn took this information and integrated it into her own practice, creating guidelines for early cancer detection that were revolutionary at the time—for instance, checking patient health histories, checking family histories, performing routine pap smears, and screening patients for cancer even before they showed symptoms. For years, Chinn was the only black female doctor working in Harlem, and she continued to work closely with the poor and advocate for early cancer screenings until she retired at age 81.
Alice Ball
Pictorial Press Ltd/Alamy
Alice Ball was a chemist best known for her groundbreaking work on the development of the “Ball Method,” the first successful treatment for those suffering from leprosy during the early 20th century.
In 1916, while she was an undergraduate student at the University of Hawaii, Ball studied the effects of Chaulmoogra oil in treating leprosy. This oil was a well-established therapy in Asian countries, but it had such a foul taste and led to such unpleasant side effects that many patients refused to take it.
So Ball developed a method to isolate and extract the active compounds from Chaulmoogra oil to create an injectable medicine. This marked a significant breakthrough in leprosy treatment and became the standard of care for several decades afterward.
Unfortunately, Ball died before she could publish her results, and credit for this discovery was given to another scientist. One of her colleagues, however, was able to properly credit her in a publication in 1922.
Henrietta Lacks
onathan Newton/The Washington Post/Getty
The person who arguably contributed the most to scientific research in the last century, surprisingly, wasn’t even a scientist. Henrietta Lacks was a tobacco farmer and mother of five children who lived in Maryland during the 1940s. In 1951, Lacks visited Johns Hopkins Hospital where doctors found a cancerous tumor on her cervix. Before treating the tumor, the doctor who examined Lacks clipped two small samples of tissue from Lacks’ cervix without her knowledge or consent—something unthinkable today thanks to informed consent practices, but commonplace back then.
As Lacks underwent treatment for her cancer, her tissue samples made their way to the desk of George Otto Gey, a cancer researcher at Johns Hopkins. He noticed that unlike the other cell cultures that came into his lab, Lacks’ cells grew and multiplied instead of dying out. Lacks’ cells were “immortal,” meaning that because of a genetic defect, they were able to reproduce indefinitely as long as certain conditions were kept stable inside the lab.
Gey started shipping Lacks’ cells to other researchers across the globe, and scientists were thrilled to have an unlimited amount of sturdy human cells with which to experiment. Long after Lacks died of cervical cancer in 1951, her cells continued to multiply and scientists continued to use them to develop cancer treatments, to learn more about HIV/AIDS, to pioneer fertility treatments like in vitro fertilization, and to develop the polio vaccine. To this day, Lacks’ cells have saved an estimated 10 million lives, and her family is beginning to get the compensation and recognition that Henrietta deserved.
Dr. Gladys West
Andre West
Gladys West was a mathematician who helped invent something nearly everyone uses today. West started her career in the 1950s at the Naval Surface Warfare Center Dahlgren Division in Virginia, and took data from satellites to create a mathematical model of the Earth’s shape and gravitational field. This important work would lay the groundwork for the technology that would later become the Global Positioning System, or GPS. West’s work was not widely recognized until she was honored by the US Air Force in 2018.
Dr. Kizzmekia "Kizzy" Corbett
TIME Magazine
At just 35 years old, immunologist Kizzmekia “Kizzy” Corbett has already made history. A viral immunologist by training, Corbett studied coronaviruses at the National Institutes of Health (NIH) and researched possible vaccines for coronaviruses such as SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome).
At the start of the COVID pandemic, Corbett and her team at the NIH partnered with pharmaceutical giant Moderna to develop an mRNA-based vaccine against the virus. Corbett’s previous work with mRNA and coronaviruses was vital in developing the vaccine, which became one of the first to be authorized for emergency use in the United States. The vaccine, along with others, is responsible for saving an estimated 14 million lives.On today’s episode of Making Sense of Science, I’m honored to be joined by Dr. Paul Song, a physician, oncologist, progressive activist and biotech chief medical officer. Through his company, NKGen Biotech, Dr. Song is leveraging the power of patients’ own immune systems by supercharging the body’s natural killer cells to make new treatments for Alzheimer’s and cancer.
Whereas other treatments for Alzheimer’s focus directly on reducing the build-up of proteins in the brain such as amyloid and tau in patients will mild cognitive impairment, NKGen is seeking to help patients that much of the rest of the medical community has written off as hopeless cases, those with late stage Alzheimer’s. And in small studies, NKGen has shown remarkable results, even improvement in the symptoms of people with these very progressed forms of Alzheimer’s, above and beyond slowing down the disease.
In the realm of cancer, Dr. Song is similarly setting his sights on another group of patients for whom treatment options are few and far between: people with solid tumors. Whereas some gradual progress has been made in treating blood cancers such as certain leukemias in past few decades, solid tumors have been even more of a challenge. But Dr. Song’s approach of using natural killer cells to treat solid tumors is promising. You may have heard of CAR-T, which uses genetic engineering to introduce cells into the body that have a particular function to help treat a disease. NKGen focuses on other means to enhance the 40 plus receptors of natural killer cells, making them more receptive and sensitive to picking out cancer cells.
Paul Y. Song, MD is currently CEO and Vice Chairman of NKGen Biotech. Dr. Song’s last clinical role was Asst. Professor at the Samuel Oschin Cancer Center at Cedars Sinai Medical Center.
Dr. Song served as the very first visiting fellow on healthcare policy in the California Department of Insurance in 2013. He is currently on the advisory board of the Pritzker School of Molecular Engineering at the University of Chicago and a board member of Mercy Corps, The Center for Health and Democracy, and Gideon’s Promise.
Dr. Song graduated with honors from the University of Chicago and received his MD from George Washington University. He completed his residency in radiation oncology at the University of Chicago where he served as Chief Resident and did a brachytherapy fellowship at the Institute Gustave Roussy in Villejuif, France. He was also awarded an ASTRO research fellowship in 1995 for his research in radiation inducible gene therapy.
With Dr. Song’s leadership, NKGen Biotech’s work on natural killer cells represents cutting-edge science leading to key findings and important pieces of the puzzle for treating two of humanity’s most intractable diseases.
Show links
- Paul Song LinkedIn
- NKGen Biotech on Twitter - @NKGenBiotech
- NKGen Website: https://nkgenbiotech.com/
- NKGen appoints Paul Song
- Patient Story: https://pix11.com/news/local-news/long-island/promising-new-treatment-for-advanced-alzheimers-patients/
- FDA Clearance: https://nkgenbiotech.com/nkgen-biotech-receives-ind-clearance-from-fda-for-snk02-allogeneic-natural-killer-cell-therapy-for-solid-tumors/Q3 earnings data: https://www.nasdaq.com/press-release/nkgen-biotech-inc.-reports-third-quarter-2023-financial-results-and-business