Can aging be slowed? Some academic scientists think so

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Visitors to the Human Longevity Laboratory, part of the Potocsnak Longevity Institute at Northwestern University Feinberg School of Medicine, spend up to three hours undergoing a battery of tests.

Physicians assess patients' cardiovascular, neurological, and muscular systems, and measure body composition using tools such as DEXA scanning to quantify fat, muscle, and bone. From a blood sample, doctors analyze subtle changes in DNA, measure thousands of proteins circulating in the body, and assess how sugars are modifying components of the immune system. At the same time, artificial intelligence interprets retinal images and data from routine heart tests - all to estimate whether someone is aging faster, slower, or essentially the same as their birth date indicates. The result is a patient's biological age, as opposed to their chronological age.

The lab's effort is part of a larger quest to unlock the secrets of aging and identify ways to slow or even reverse the processes that lead to diseases such as cancer, heart disease, diabetes, and neurodegenerative conditions. These diseases often lead to months or years of illness and disability at the end of life.

"We've come to understand that age is the most important risk factor for almost every disease we deal with in adult human beings," says Douglas Vaughan, MD, the institute's director. "If we can slow down aging even a bit, we can push back the onset of disease and extend the health span of our species."

Northwestern is one of several academic health centers around the country that have longevity-focused institutes and clinics. Others include the University of Texas (UT) at San Antonio, Cedars-Sinai Medical Center in Los Angeles, the University of Washington in Seattle, and the Albert Einstein College of Medicine in New York City. These centers aim to increase the years people remain free of disease and compress the time they may face life-ending illnesses. The physicians and scientists who work in these centers conduct a wide range of research, create registries of aging patients, and even provide care for people with age-related concerns and others who want to prevent such problems from starting in the first place.

"We want to target your aging before you have diseases," says Nir Barzilai, MD, director of the Institute for Geroscience at the Albert Einstein College of Medicine, who holds several leadership positions in the burgeoning field.

The geroscience revolution

Lifestyle and environmental factors, such as exercise, nutrition, sleep, social connection, and managing life stress, account for about 80% of aging (the other 20% is due to genetics). In fact, adopting healthy habits has been consistently linked to a longer lifespan.

Walking is a good example. Taking 10,000 steps a day, the equivalent of four and a half to five miles, lowers the risk of an early death by 36%, compared with being sedentary, research shows. And sleeping well each night can add as many as five years to the average lifespan, other data suggest.

But geroscientists (those focused on understanding the biological mechanisms of aging, in order to delay or treat age-related diseases) believe that more significant gains in both longevity and, crucially, health span - the years of healthy life - are possible. They have identified roughly 12 interconnected hallmarks of aging, which provide targets for drug development and other interventions. These hallmarks include the shortening of telomeres (the protective caps on the ends of chromosomes), chronic inflammation, genomic instability (the accumulation of DNA damage and mutations over time), and cellular senescence (when damaged cells in the body stop dividing and accumulate in tissues, promoting age-related diseases).

"They're all involved in one way or the other in the development of those diseases that are linked to aging," says Elena Volpi, MD, PhD, director of the Sam and Ann Barshop Institute for Longevity and Aging Studies at UT San Antonio. "The idea of geroscience is that we want to find interventions that can modify more than one of those mechanisms."

For instance, scientists have known for decades that extreme calorie restriction increases longevity; a 35% to 40% reduction in calorie intake significantly extends lifespan and improves health in animal models, though such calorie restriction is challenging in people.

However, following a low-calorie, nutrient-rich diet for five days a month for three months, sometimes called fasting mimicking, appears to mirror the biological effects of calorie restriction, reducing disease risk factors and slowing biological aging in healthy adults, according to research.

Old drugs, new benefits

Novel medications for longevity are in development, but many experts see drugs approved by the Food and Drug Administration (FDA) for other purposes as low-hanging fruit that could yield encouraging results. In his work as head of the Academy of Health and Lifespan Research, Barzilai and his colleagues have identified a number of already available drugs that show promise for testing in human trials.

Intriguing evidence from animal and epidemiology studies has pointed scientists toward the diabetes drug metformin and the immunosuppressant rapamycin. Based on their effects on multiple body systems, products such as GLP-1 receptor agonists, SGLT2 inhibitors, and even the osteoporosis drugs known as bisphosphonates are also viewed as possible candidates.

For example, "SGLT2 inhibitors, which were designed to eliminate glucose from the kidneys, are now shown to improve kidney function and cardiac function and to provide a more global benefit in the health of patients," says Volpi.

In some cases clinical trials are planned or are underway, though investigators must contend with regulatory and funding challenges. The FDA doesn't recognize aging as a disease, which makes clinical trials hard to define. Drug manufacturers are also less inclined to fund studies of inexpensive older drugs, say experts.

"The problem we've got is that in the current environment, the incentive structures are all aligned against getting the data we would all like to see," says Matt Kaeberlein, PhD, founder of the Healthy Aging and Longevity Research Institute at the University of Washington, and cofounder and CEO of Optispan, a Seattle-based longevity-medicine clinic.

Meanwhile, such drugs are sometimes prescribed off label for their longevity benefits. "It's legal for your doctor to give you any one of these drugs," says Barzilai.

Many clinicians, though, see them as options for patients who are already candidates for the medications.

"We want to provide evidence-based care for healthy longevity, but we don't really have the evidence yet," says Volpi. "When looking at the individual patients, we should look at the whole package and see what current diseases and conditions they have. Where there are risk factors, then you can act."

Doctors are hopeful that new options will soon be available.

Here are snapshots of initiatives from a few longevity labs and clinics.

The Human Longevity Laboratory at Northwestern University Feinberg School of Medicine

The work of the laboratory, which was launched in 2022, stems in part from Vaughan's research with an Amish population of about 20,000 people in northwestern Indiana. A gene mutation common in the community allows carriers to live an average of 10 years longer than others. About 10% of the population carries this genetic variant, Vaughan says.

"They have longer telomeres, they don't get diabetes, they have preserved vascular function later in life, and they live longer," he says.

The lab's research is focused on developing approaches to switching off the age-related gene in people who lack the favorable mutation. And researchers are conducting a clinical trial to see how the use of stress-calming exercises on an app affects participants' biological aging.

"We're also trying to build a network of similar laboratories around the country and the world, with the same platform, tools, and approach, to test interventions," says Vaughan, who has connected with colleagues in South Africa, Brazil, and the Middle East, among others.

"We're in such an interesting scientific space in the world of aging right now, because the biology of aging has been largely demystified," he says. "We know a lot more about aging now than we did 20 or 30 years ago. And simultaneously, we now have the ability to measure biological age with precision, which never existed before."

The Institute for Geroscience at Albert Einstein College of Medicine

The institute was established in 2001, and its work spans basic and clinical research - from cellular processes to studies of brain aging and centenarian genetics - with the goal of extending health span. Through the institute's Longevity Genes Project, Barzilai and his team have conducted genetic research on more than 800 centenarians - healthy elderly people between ages 95 and 112, and their children. The researchers hope that identifying longevity-related genes could lead to new drug therapies.

"My centenarians not only live longer. They live healthier, and they're sick very little at the end of their life," says Barzilai. "That's what we want. That's the vision."

Existing pharmaceuticals represent another area of research. Several of the institute's investigators have designed, together with the FDA, a trial called Targeting Aging with Metformin (TAME), and there's interest in developing other gerotherapeutics.

"Studies show that metformin, SGLT2 inhibitors, and GLP-1 receptor agonists prevent cardiovascular disease, diabetes, and kidney disease, and may also prevent Alzheimer's disease," says Barzilai. "They are very powerful drugs."

The institute recently launched the BIO-VITAL (Batia and Idan Ofer Center for Validation of Interventions Targeting Aging and Longevity) program, in an effort to rigorously evaluate potential longevity interventions - testing whether the use of drugs or other approaches affect the biological processes of aging. The program offers standardized, independent testing to biotechnology and pharmaceutical companies, as well as academic collaborators.

The Barshop Institute for Longevity and Aging Studies at UT San Antonio

The institute has a rich history of basic research into aging and longevity, dating back three decades. Significantly, Barshop published the first study demonstrating the effectiveness of the repurposed drug rapamycin in extending longevity in mice in 2009.

The study was conducted in conjunction with the Jackson Laboratory in Bar Harbor, Maine, and the University of Michigan in Ann Arbor, as part of the National Institutes of Health's Interventions Testing Program. The NIH subsequently investigated other agents for life-lengthening qualities, including the diabetes drugs acarbose and SGLT2 inhibitors, in mice.

Now Barshop is increasingly turning to trials in humans. "Our mission is to rapidly move our findings on the very basic mechanisms of aging into the clinical world," says Volpi.

Barshop recently received funding to test whether three FDA-approved medications can slow age-related decline in healthy older adults.

"We're going to test rapamycin, dapagliflozin [an SGLT2 inhibitor], and semaglutide [a GLP-1 receptor agonist] head to head, to see if they can prevent the decline in 'intrinsic capacity' in a population of people in their 60s," Volpi says. This composite index for healthy aging measures locomotion, cognitive function, psychological function, vitality, and sensory function.

The trial is set to start in 2027.

The Healthspan Clinic at Cedars-Sinai Medical Center

Patterned after a similar center at the Mayo Clinic, the Healthspan Clinic is the newest to focus on helping patients boost their long-term health and remain independent as long as possible.

"The idea behind the clinic is to help patients develop a plan for healthy aging that is based on evidence and provide an opportunity for patients who might be interested in participating in research," says Sara Espinoza, MD, the clinic's medical director.

People seeking care first undergo a comprehensive evaluation of their physical and cognitive health, lifestyle habits, and overall condition. The clinic's recommendations for healthy aging come from established guidelines, including adopting a plant-forward diet with healthy fats and whole grains. The clinic also focuses on achieving or maintaining an optimal weight and stresses the importance of proper sleep and social engagement.

Patients may be offered the opportunity to participate in clinical trials at Cedars-Sinai, such as one studying the effects of senolytic medications, overseen by Nicolas Musi, MD, director of the Diabetes and Aging Center at Cedars-Sinai. These medications are a class of experimental therapies designed to eliminate senescent cells, those that have stopped dividing but don't die off as they should and thus promote disease.

"The study is comparing senolytic medications with lifestyle interventions in young and older adults who are both obese and lean," says Espinoza.

Patients at the clinic can also contribute to a biorepository that collects blood samples and other data to track biomarkers linked to the onset or progression of disease.

"It's a pretty exciting time," says Espinoza. "We feel there could be significant discoveries in the next few years. But there's still much work to be done, especially around the area of biomarker discovery and identifying what type of patient is appropriate for what type of intervention. Aging research is a work in progress."