Key Points:
- Agreed-upon blood markers of aging, such as insulin growth factor (IGF-1), can predict cardiovascular disease and metabolic disorders.
- Other blood markers pertain to systemic inflammation, such as interleukin-6 (IL-6), high levels of which are associated with heart disease and chronic inflammation.
- Some of the markers of aging relate to physical function, such as a test of grip strength, and others pertain to DNA molecular tagging patterns (DNA methylation) used to predict biological age—an age assessment reflecting potential longevity.
Published in the Journals of Gerontology, 60 aging research experts from various international institutions, including the University of Pennsylvania and the Germany-based Max Planck Insitute for Biology and Ageing, arrived at a consensus to designate markers of aging—referred to as biomarkers. These aging markers included some related to physiological function, inflammation, physical function, or DNA methylation patterns used to assess biological age. At the end of three rounds of suggesting, recommending, and rejecting biomarkers of aging, the panel of experts arrived at a consensus where 70% or more of the experts agreed on 14 specific biomarkers of aging.
Since no large consortium had agreed on a set of biomarkers of aging previously, these 14 biomarkers may serve as a starting point for assessing the efficacy of aging interventions. In that sense, in future studies, researchers can test whether treating older adults with certain therapeutics alleviates aging, according to tests done with these biomarkers.
Physiological Biomarkers of Aging
Two identified physiological biomarkers relating to overall physiological function are assessed through blood tests: insulin-like growth factor 1 (IGF-1) and growth-differentiation factor 15 (GDF-15). IGF-1 is a hormone that plays a crucial role in growth, development, and metabolism, and lower levels in older adults are associated with conditions like frailty and cognitive impairment. GDF-15, on the other hand, is a hormone that regulates metabolism and appetite, and elevated GDF-15 in older adults is associated with cardiovascular disease and dysfunctional metabolism. Accordingly, low IGF-1 and elevated GDF-15 are associated with reduced physiological functioning related to physical vigor, cognition, cardiovascular well-being, and metabolism.
Inflammatory Biomarkers of Aging
Two biomarkers of aging labeled as inflammation-related are also assessed with blood tests: high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). hsCRP is an inflammatory protein produced primarily in the liver in response to inflammation in the body, and high hsCRP levels are associated with an elevated risk for heart disease. The other inflammatory blood marker, IL-6, is a protein with key roles in inflammation and the immune response, and elevated levels of IL-6 are associated with cardiovascular issues, cancer, liver disease, diabetes, and Alzheimer’s disease. As such, hsCRP and IL-6 blood tests can suggest problems related to the cardiovascular system, cancer, the liver, metabolism, or neurodegenerative conditions.
Biomarkers of Aging Related to Physical Function
The experts’ consensus included nine biomarkers of physical function. These physical functioning biomarkers were muscle mass, muscle strength, hand grip strength, the timed-up-and-go test, gait speed, the standing balance test, frailty index, cognitive health, and blood pressure.
Muscle mass refers to the total weight of muscle tissue in the body. Low muscle mass in older adults is associated with conditions like diabetes, heart failure, and arthritis. Thus, low muscle mass may infer ailments related to metabolism, cardiovascular function, and joint health.
Muscle strength, another physical function-related biomarker of aging, is the ability of muscles to exert force against resistance. In older adults, having low muscle strength is associated with age-related diseases like diabetes, heart disease, cancer, frailty, and osteoporosis. Accordingly, low muscle strength can suggest metabolic, cardiovascular, cancer-related, or bone-related conditions.
Another biomarker of aging, hand grip strength, refers to the force exerted by muscles in the hand and forearm when squeezing an object. Low hand grip strength is associated with numerous age-related conditions like heart disease, diabetes, kidney disease, liver disease, cancer, and cognitive impairment. Thus, low hand grip strength suggests age-related diseases associated with the cardiovascular system, metabolism, the kidney, the liver, or the nervous system.
Another physical function-related biomarker of aging, the timed-up-and-go test, assesses a person’s functional mobility and risk for falls. For a brief description, the test measures the time it takes to stand up from a chair, walk a short distance, turn, and sit down again. Taking a longer time to perform this task is often considered a sign of an increased risk for falls. Since 78.0 out of 100,000 older US adults died from falling in 2021, a lower time on this test may suggest a reduced chance of mortality from a fall.
Gait speed, another physical function-related biomarker, refers to how quickly someone can walk a specific distance on a level surface. Our gait speed typically declines as we get older, and lower gait speeds can be used to predict falls, hospitalization, and mortality. Furthermore, research suggests that consistent walking combined with strength training may improve gait speed in older adults. Improving gait speed may thus serve as a way to reduce the risk of falls.
The standing balance test, another agreed-upon biomarker of aging, assesses an individual’s ability to maintain balance while standing and performing various movements. This test can be used to suggest age-related visual issues and nerve damage. As such, the researchers associated poor performance on this test with aging.
Another biomarker of aging, the frailty index, represents the accumulation of health problems in an individual. Scored from 0 to 1, a score at or above 0.35 would suggest moderate to severe frailty—the age-related condition of being weak. Interestingly, the frailty index can be improved with interventions like physical activity, dietary changes, and possibly future aging intervention therapeutics.
Cognitive health, a biomarker of aging, is the ability to think, learn, and remember clearly. This metric also encompasses functions like reasoning, problem-solving, and decision-making. Cognitive health can be assessed with certain neurocognitive tests, and poor cognitive health may suggest cognitive decline or dementia. An aging intervention therapeutic that improves this biomarker of aging may effectively slow or reverse cognitive aging.
Finally, the last physical function-related biomarker of aging, blood pressure, refers to the force of blood pushing against artery walls as the heart pumps blood throughout the body. High blood pressure, a condition known as hypertension, puts people at risk for a stroke, heart attack, or other cardiovascular problems. If certain aging intervention therapeutics reduce blood pressure in hypertensive patients, this may support their efficacy against this aspect of aging.
DNA Methylation Patterns as a Biomarker of Aging
DNA methylation-based aging clocks, first developed in 2011, have been used to predict individuals’ biological age. Interestingly, the consortium of aging experts from this study identified these aging clocks as biomarkers of aging. In that sense, any future aging intervention therapeutic that reverses biological age as predicted with any of these clocks may effectively work against the ravages of aging.
Figuring Out What Combinations of the 14 Biomarkers of Aging to Use
Aside from agreeing on these 14 biomarkers of aging related to physiology, inflammation, physical function, and DNA methylation, figuring out which combination of biomarkers to use for assessing the efficacy of aging interventions will be key. Perhaps measuring the effects on all of them at once over the course of six months to a year would suffice. Researchers studying the efficacy of aging interventions must analyze these biomarkers to determine which of them most effectively represents aspects of aging.
Whatever the case may be, having this list of biomarkers of aging will serve as a solid start in evaluating currently-researched or future aging intervention strategies. Along those lines, some strengths associated with this list are that it came from a multi-national consortium of aging experts and that 60 of these experts completed the full assessment of biomarkers. Future analyses of biomarkers of aging may also reflect on the methods used to generate these 14 biomarkers of aging to potentially improve upon these biomarkers used to gauge the effectiveness of aging intervention therapeutics.
Comments