The First Hundred Years: Healthy Longevity May Ultimately Define the Future
Humankind has eternally searched for the fabled fountain of youth. While we suspect that a magical elixir to turn back time may never be discovered, in 2023 we are coming ever closer to a more achievable goal: using scientific breakthroughs to slow the process of aging and therefore prolong our healthspan. As the number of Americans celebrating their 90th, 95th and even 100th birthdays continues to rise, aging research has radically shifted from efforts to extend the lifespan to enhancing function and years lived independently. Countless studies, encompassing everything from launching stem cells into space to investigating the genetics of “super agers”, are underway. Below we explore some of the newest thinking and exciting breakthroughs to come with nationally recognized expert George Kuchel, MD, whose decades of successful research both at the bench and in clinical settings have contributed to shaping a new vision of how we age.
“We can’t reach old age by another man’s road. My habits protect my life but they would assassinate you.” – Mark Twain, 1905
Individuality in Aging
“We used to look at older adults as if they were all the same, with everyone becoming old the day they retired at 65,” says Dr. Kuchel, director of the UConn Center on Aging, which was established in 1985, making it one of the first multidisciplinary centers focused on improving the lives of older adults through research, education and clinical care. “While aging is inevitable and a normal part of the lifespan process, there’s tremendous heterogeneity, or variability, in how each of us ages. When we study the rate at which individuals age in terms of physical and cognitive function, frailty, disability, and disease development, we find increasing heterogeneity with age. Therefore, rather than focusing on averages typically culled from observational studies of older people compared to younger people, we are focusing on the differences within those averages.”
Geroscience and Aging Adults
Better understanding the uniqueness of each individual as they age has inspired Dr Kuchel and his colleagues to spearhead the burgeoning new field of Precision Gerontology. The overarching goal is to develop treatments for older patients that are more effective in promoting health and independence by being more precise and targeted. Adding exponentially to this knowledge base is the field of Geroscience, which seeks to delay the onset and progression of different chronic diseases by targeting the shared biological mechanisms that make aging a major risk factor and driver of common chronic conditions and diseases of older people.
“Many older people have multiple ongoing chronic conditions, and see different physicians for each,” says Kuchel. “However, as geriatricians and concierge medicine physicians were among the first to recognize, looking at the whole patient is essential. Geroscience transforms the ‘one disease at a time’ approach by studying the role of biological aging in enabling all these conditions.”
The 2021 launch of the NIA Older Americans Independence “Pepper” Center at UConn, one of only 15 National Institutes of Health (NIH)-funded centers across the country dedicated to enhancing function and independence in older adults through research, has significantly advanced the scope of studies at the university. According to Kuchel, “We are combining evidence-based geriatric care with more individualized treatments involving emerging interventions designed to delay the onset of chronic diseases by targeting biological aging. Our work moves us closer to the mission of extending the healthspan of greater numbers of individuals.”
Studies Related to Healthy Aging and Longevity
Promising studies under the microscope at UConn and other prominent research institutions include:
Can chronic diseases be delayed by targeting aging?
A geroscience-based trial to test the effectiveness of diabetes drug metformin in slowing the onset of chronic diseases in older adults is slated to be announced in 2023. The randomized, six-year TAME (Targeting Aging with Metformin) trial, led by the American Federation for Aging Research, will engage over 3,000 individuals nationwide between the ages of 65 and 79 to test if those taking metformin experience decreased or delayed onset or progression of age-related diseases such as cardiovascular disease, cancer and dementia.
Dr. Kuchel believes that conducting the trial will prove revolutionary. “Metformin has an excellent safety profile, proven over more than six decades,” he says, “and uniquely among other oral hypoglycemics, it appears to have a broad effect on many aspects of aging.” By collecting and analyzing trial participants’ serum, plasma, blood, urine and stool for varied biomarkers, the study will also provide information about a person’s risk of developing a disease, and lay a solid foundation for future biomarker discovery and validation as well as accelerating the pace of geroscience research.
Worth noting: In earlier stages is the study of rapamycin, an immunosuppressant currently used in high doses in transplant patients. However, when used in much lower doses the drug promotes longevity and reduces age-related disease in animal models, while it improves influenza vaccine responses in community-dwelling older adults.
This entirely new class of drugs may one day be used to halt cellular senescence, a hallmark of aging. As cells age and lose their ability to divide, they secrete molecules that trigger inflammation and cause much of the damage seen in osteoporosis, arthritis, diabetes, sarcopenia, cardiovascular disease and cancers. In numerous animal trials, use of senolytic drugs such as fisetin to selectively eliminate and clear senescent cells from the body were shown to significantly improve function. Multiple placebo-controlled, double-blind studies with older patients are planned or underway through the National Institute of Aging Translational Geroscience Network and elsewhere.
Inside the microbiome
This topic of intense interest continues to build an impressive body of research, including a recently completed collaboration between UConn Center on Aging and Julia Oh, PhD, at the Jackson Laboratory for Genomic Medicine on the same campus. This study showed the presence of an altered microbiome (the millions of microbes living in our gut, mouth, skin and elsewhere) in nursing home residents. Importantly, the changes were specific to frailty rather than biological age, and linked to bacteria associated with severe infections and antibiotic resistance. Going forward, in keeping with a focus on Precision Gerontology, clinical approaches may be used to identify individuals with high risk for severe infections and to explore treatments for restoring the microbiome to a state characteristic of younger or less frail individuals.
Personalized influenza vaccines
Another example of Precision Gerontology research is underway with Duyu Ucar, PhD, at the Jackson Laboratory and the Icahn School of Medicine at Mount Sinai, studying adults aged 65 and older over the next three influenza seasons to pinpoint the age-related immune alterations that reduce influenza vaccine effectiveness. “We know the body’s ability to produce a robust immune response after receiving the flu shot decreases with age, and we’ll be testing whether next-generation influenza vaccines, including mRNA-based ones, can help boost these immune responses. Understanding the factors that predict good responses to each vaccine will allow us to ultimately personalize our recommendations,” explains Kuchel.
“This is truly a time of meaningful change and ongoing advances in the field of aging,” says Kuchel. “Each day we uncover new answers to the question that has inspired our research from the start: ‘How can we add life to our years?’”
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