A routine blood sample may one day reveal more than whether an older person has kidney disease, diabetes or another medical problem.
It could also provide clues about whether someone who is independent today is at increased risk of needing help with everyday life in the future.
Researchers from Keio University in Japan have identified two blood proteins that appear to predict future disability in adults of very advanced age. The proteins are called beta-2-microglobulin, or B2M, and cystatin C.
The discovery comes as societies around the world face a major demographic change. People are living longer, which means more adults are reaching their 80s and 90s, but longer life does not always mean more years of independent living.
Japan offers a clear example of this challenge. Nearly six in ten Japanese adults aged 85 or older receive support through the country’s Long-Term Care Insurance system, creating growing demand for carers, medical services and public funding.
Preventing disability is therefore becoming just as important as treating individual diseases. If doctors could recognize a person’s risk several years earlier, they might have time to strengthen muscles, improve nutrition, treat health problems and reduce other causes of physical decline.
Associate Professor Yusuke Osawa and colleagues began by studying adults aged 85 to 89 who were still living independently. Their analysis included 230 disability-free participants in the Kawasaki Aging Well-being Project.
Rather than choosing one suspected blood marker in advance, the researchers screened 29 proteins circulating in plasma. They then used machine learning and other statistical methods to look for patterns connected with later disability and death.
The participants were followed for roughly four and a half years. During that period, higher B2M and cystatin C levels consistently identified people who had a greater chance of becoming disabled.
The statistical results suggested that rising B2M was associated with a 35% increase in disability risk, while rising cystatin C was associated with a 42% increase. These associations remained even after the researchers adjusted for several other health and lifestyle factors.
Finding a pattern in one relatively small study is not enough to establish a useful medical marker. The researchers therefore tested the results using data from another major aging project thousands of kilometers away.
The second group came from the Invecchiare in Chianti, or InCHIANTI, study in Italy. Some participants in this long-running project had been followed for up to 15 years.
Once again, people with higher B2M and cystatin C were more likely to develop disability. The association was particularly noticeable in adults aged 80 and above.
This second result matters because Japanese and Italian populations differ in diet, lifestyle, environment and health care. When the same biological signal appears in separate populations, it reduces the possibility that the original result was caused by a local or accidental factor.
Both proteins may also tell scientists something about why physical independence declines with age. B2M and cystatin C are related to kidney function, an important part of health that can gradually weaken as people become older.
B2M is also associated with chronic low-level inflammation. Unlike the short burst of inflammation that helps the body fight an infection or heal an injury, this quieter form can persist for years.
Researchers sometimes refer to age-related chronic inflammation as inflammaging. It has been linked with frailty and several illnesses associated with aging, although scientists are still working out exactly how these processes interact.
The attraction of B2M and cystatin C is also practical. They are not mysterious experimental substances that require an unusual laboratory, because clinical tests capable of measuring them already exist.
That does not mean doctors should immediately begin using the proteins to decide who will become disabled. Researchers first need to establish what levels are meaningful, how measurements change over time and whether the tests add useful information to assessments doctors already perform.
The study also searched for blood proteins related to the risk of death. Some candidates appeared promising in the Japanese analysis, but they did not produce the same results when tested in the Italian population.
This failure to repeat the mortality findings is scientifically useful. It shows the danger of treating an initial association as a proven result and makes the successful replication of B2M and cystatin C more significant.
The research, involving scientists from Keio University and the National Institute on Aging in the United States, was published online in GeroScience. It suggests that biological changes connected with kidney health and inflammation may begin signaling future loss of independence before disability becomes obvious.
The study’s design has several strengths, especially its focus on very old adults who were initially free of disability and its independent validation in another country. At the same time, the Japanese discovery group included only 230 people, so much larger studies will be needed.
Blood markers also cannot capture every reason an older adult may lose independence. Falls, arthritis, dementia, stroke, social isolation, poor nutrition and many other factors can affect whether someone eventually needs help.
The most useful future test will be whether these markers lead to action that actually works. Identifying high-risk people has little value unless early exercise, rehabilitation, nutrition or medical treatment can reduce that risk.
If future research confirms that such interventions help, B2M and cystatin C could become part of a shift in aging care. Instead of waiting until an older person becomes dependent, doctors might be able to recognize vulnerability earlier and work to preserve independence while there is still time to make a difference.
Source: Keio University.
