A team from Keio University (Japan) has found two proteins present in the blood that are consistently related to the risk of future disability in people aged 85 or older, an advance that could facilitate the detection of those who are more vulnerable.
Japan is one of the countries where aging is advancing most rapidly. Almost 60 percent of Japanese people aged 85 or older already receive support through the national Long-Term Care Insurance system, which underscores the urgency of locating those at risk before a disability appears.
Although routine blood tests allow for the diagnosis of many pathologies linked to aging, until now it has been difficult to find solid biomarkers capable of anticipating future disability in the oldest elderly. Having these indicators would allow for earlier action and help people remain active and independent for longer.
To address this challenge, a group led by associate professor Yusuke Osawa from the Graduate School of Health Management at Keio University, along with professor Yasumichi Arai from the Faculty of Nursing and Medical Care of the same institution, and Dr. Luigi Ferrucci, scientific director of the Translational Gerontology Division of the National Institute on Aging of the National Institutes of Health in the United States, examined blood samples from adults aged 85 to 89 who resided in the community, using a data-driven analysis of circulating proteins without prior hypotheses.
Using machine learning techniques and multivariable statistical models, they analyzed 29 plasma proteins to assess their relationship with the onset of disability and future mortality. They then independently validated the results in the Italian aging study Invecchiare in Chianti (InCHIANTI). The conclusions have been published in the journal 'GeroScience'.
B2M and cystatin C, in the spotlight
The initial analysis was conducted with 230 participants without disability from the Kawasaki Aging Well-being Project (KAWP), followed for about 4.5 years. High levels of beta-2-microglobulin (B2M) and cystatin C were consistently linked to a higher likelihood of developing disability.
Each increase in the concentration of these biomarkers was associated with a significant increase in the risk of disability, even after adjusting for age, sex, kidney function, lifestyle, and other possible confounding factors.
To verify whether the findings could be extrapolated to other contexts, the team examined participants from the InCHIANTI study, which has followed older individuals in Italy for up to 15 years. Again, elevated levels of B2M and cystatin C were related to a higher risk of disability, especially among those aged 80 or older.
In contrast, the proteins initially associated with mortality - such as epidermal growth factor and interferon gamma-induced protein 10 - did not show reproducible results, suggesting that the biomarkers linked to disability were the most robust finding of the work.
"Since B2M and cystatin C can already be measured through conventional clinical analyses, they have the potential to become practical tools for identifying older individuals who could benefit from preventive measures," notes Osawa.
Both proteins also help to better understand the biological processes involved. They are related to kidney function and, in the case of B2M, also reflect chronic low-grade inflammation, known as inflammaging or inflammation associated with aging, increasingly recognized as a factor driving age-related decline. Together, these mechanisms could favor the gradual loss of physical capacity that ultimately leads to the need for long-term care services.
"Our results suggest that to preserve healthy aging, it is not only necessary to pay attention to diseases but also to the biological processes that precede disability. Identifying individuals at higher risk earlier could open the door to timely interventions, such as exercise, nutritional support, and rehabilitation, before irreversible decline occurs," explains Arai.
From reaction to prevention
Overall, the work positions B2M and cystatin C as promising blood biomarkers of future disability in very elderly individuals. Their validation in cohorts from Japan and Italy supports their possible application for earlier detection of risk in rapidly aging societies.
This approach could facilitate the transition from a healthcare model focused on treating the problem once it has appeared to another based on proactive prevention, contributing to more elderly people maintaining their autonomy and, at the same time, alleviating the growing pressure on long-term care systems globally.