The Results of Most Potential Biomarkers of Aging Vary Considerably

As expected, a study finds that the numerous candidate biomarkers of aging vary widely in their assessments of biological age. This makes complete sense, as (a) aging is caused by a number of distinct processes of damage accumulation, and (b) most of the assessments measure one or more metrics that are more influenced by some forms of damage than by others. To pick an easy example, when measuring aging by skin-related metrics such as wrinkles, appearance, and elasticity, what is seen is primarily the consequences of cross-linking. If measuring fibrosis in organs, then that is primarily cellular senescence and immune system dysfunction. If measuring grip strength, falling numbers here are caused by the contributions to sarcopenia, which so far appears to be caused primarily by failing stem cell activity.

Of all of the potential biomarkers of aging, I would hypothesize that those based on patterns of DNA methylation are the best to date, as they likely measure blended cellular responses to all of the forms of damage that cause aging. That said, it is thought-provoking to see the evidence here suggest that a suitable combination of simple measures such as grip strength and bloodwork is more effective. The conclusion that biomarkers of aging are still a work in progress is no doubt an accurate one.

A head-to-head comparison of 11 different measures of aging, including blood and chromosome tests like those being sold commercially, has found that they don't agree with one another on how fast a given person is growing older. This comparison is based on a life-long study of nearly 1,000 people in Dunedin, New Zealand who have been studied extensively from birth to age 38. Researchers working with this study cohort had earlier reported that a panel of 18 biological measures might be used to predict the pace of aging, based on how these markers had changed from age 26 to 38 in a given individual. But when they expanded their analysis to look at whether these measures and others all pointed in the same direction at age 38, the picture was much less clear.

"People age at different rates and geriatric medicine needs a way to measure that, but when measuring all sorts of different aspects of a person's physiology, from genes to blood markers to balance and grip strength, you see a lot of disagreement. Based on these results, I'd say it's premature to market aging tests to the public."

For comparisons, the researchers drew on physical measures of aging collected from the Dunedin study group, including balance, grip, motor coordination, physical limitations, cognitive function and decline, self-reported health and facial aging as judged by others. Measuring the length of telomeres, protective caps of DNA at the end of chromosomes that unravel as we age, turned up no evidence of the ability to predict physical or cognitive changes, except possibly facial aging. "Telomeres are a fundamental mechanism of aging and cancer prevention, that's true. But saying it's useful to measure in a 50-year-old to see whether they're aging is a different matter."

The team also examined hundreds of locations in the genome to see changes in the patterns of DNA methylation, molecular controls that govern whether a gene is active or not. These epigenetic patterns have been studied by other researchers as clocks thought to measure the aging rate. The researchers measured the clocks when people were 26 and again when they were 38 and found the expected 12 years of progress. The good news is that the three different epigenetic clocks they tested seem to keep time pretty well. "But the clocks were less clearly related to changes in people's physiology or problems with physical or cognitive performance. That raises questions about whether they could be used to survey patients or populations to predict health span."

The team also applied algorithms developed by other teams to analyze a large collection of physiological measures, including blood markers and tests of heart and lung function, and found a somewhat stronger signal. When they statistically examined all of their tests against each other to see whether biological aging measures could predict physical changes or mental changes, they found that the physiological measures performed somewhat better than telomeres or epigenetic clocks. But none of the measures performed well enough to argue for including them in an annual physical exam. The search will continue. As scientists investigate therapies to slow aging, "we'd like to know in less than 30 years whether the treatment works." Ideally, such a measure would be related to chronological age and would be inexpensive and non-invasive so it could be given to people before and after testing an anti-aging therapy to see whether it's working.

Link: https://today.duke.edu/2017/11/aging-tests-yield-varying-results

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