The ongoing investigation into the genetics of longevity is revealing important insights about health as we age, including the potential link to hearing health and other age-related conditions. Researchers at Washington University School of Medicine in St. Louis are utilizing an $80 million grant to further their studies through the Long Life Family Study, an extensive, international initiative focused on families that exhibit exceptional longevity, with some members living to 100 years and beyond.
Founded in 2004, the Long Life Family Study has leveraged Washington University’s prominence in genetics and genomics. Positioned as a significant contributor to the Human Genome Project, the institution aims to identify genetic factors contributing to healthy aging, particularly as the population ages and faces a rising tide of chronic illnesses such as heart disease, diabetes, and Alzheimer’s disease.
According to lead researcher Michael A. Province, PhD, understanding the genetic profile of families with remarkable longevity may shed light on how these individuals evade or postpone common age-related diseases, eventually guiding treatment and prevention strategies for healthier, longer lives.
“Most medical research concentrates on genetic issues that lead to diseases; however, I am intrigued by the opposite question: Are there genetic variants that facilitate positive outcomes in the body? Our study suggests numerous genetic possibilities enabling these long-lived families to avoid chronic diseases as they age,”
Michael A. Province, PhD
New Insights on Healthy Aging
Involving over 5,000 participants from more than 530 families residing in the U.S. and Denmark, the study tracks health patterns across generations. The inaugural group, which began enrolling in 2006, consisted of participants averaging 90 years old, with some living beyond 110. This generational design allows researchers to examine inherited genetic variations that could shield family members from typical age-related ailments. The study also compares findings with the well-established Framingham Heart Study, which has monitored families since 1948.
Recent findings from the Long Life Family Study have begun to pinpoint various health attributes associated with longevity. Different families displayed diverse traits; some excelled in cognitive health or exhibited optimal blood pressure, while others showcased exceptional lung function or grip strength. Overall, these families tend to show lower incidences of diabetes. Notably, researchers identified a genetic variant linked to lower hemoglobin A1c levels, an indicator used in diagnosing diabetes.
Many families have exhibited exceptional cardiovascular and metabolic health. However, perplexing paradoxes persist, such as the prevalence of obesity being comparable between long-lived families and those studied in Framingham, while the instance of diabetes in these longer-lived families is approximately half of what would be expected.
“Something appears to protect them from diseases typically associated with obesity,” Province noted, indicating the need for further exploration to uncover these protective factors.
Moreover, the longevity of participants has facilitated the identification of a new gene associated with late-onset Alzheimer’s disease. Interestingly, researchers also discovered a genetic variant correlated with both extreme longevity and lower blood pressure, accompanied by a slightly elevated risk for head and neck cancers. Caution is warranted in developing therapies that address rare variants due to their dual impact on health.
The study is poised to tap into the latest advancements in „Long-Read“ sequencing technology to conduct a comprehensive reanalysis of the entirety of participants‘ genomes, potentially expanding the total participant count to 7,800. This cutting-edge approach aims to explore what is often referred to as the “dark matter” of the genome, previously overlooked by older sequencing technologies, thereby revealing additional genetic clues to longevity.
As many of the oldest participants have passed, the research team is actively seeking new families with significantly long-lived relatives, particularly aiming to diversify the genetic background of their cohort, which currently comprises mostly European descendants.
“We plan to enroll more families, particularly of African descent. A larger and more diverse dataset will enable better identification of inherited genetic variants linked to longevity and help differentiate between true protective factors and those simply inherited,” Province explained. “This is a critical inquiry as we work toward finding ways to replicate these protective effects for individuals who lack the beneficial genetic variants.”
With study sites based in the U.S. and across the globe, researchers at WashU Medicine collaborate with various institutions, including Boston University and Johns Hopkins University, among others, to further this vital research into the genetics of longevity and overall health.
