Takashi Shida, Research Team for Promoting Independence and Mental Health
● Introduction
In Japan, approximately 8.7% of people aged 65 and older are classified as frail, while 40.8% are considered pre-frail, an early stage of frailty. The remaining 50.5% are categorized as robust¹. In other words, about half of the older population falls into the frail or pre-frail categories--periods during which maintaining good health can be particularly challenging.
Frailty in older adults is associated with a decline in physical functions and an increased risk of mental and social issues, such as cognitive decline and social isolation. As a result, frail individuals tend to require more social resources--including medical care, welfare services, and long-term care--compared to their robust counterparts.
Importantly, the development of frailty and other aging-related changes can vary significantly between individuals. Aging itself is a highly complex biological process, and the metabolic mechanisms behind these changes--which form the basis of metabolomics--are still not fully understood.
In this study, we introduce efforts to explore the biological mechanisms underlying frailty. Specifically, we focused on older residents of Itabashi City in Tokyo and analyzed metabolites (blood markers) in their bloodstream that are associated with frailty.
● Overview of frailty and evaluation criteria
It is widely recognized that populations around the world, including Japan, are aging. At the same time, the number of older individuals who are bedridden or require long-term care is increasing. Among them, some are classified as "frail"--a condition that lies between being healthy and needing long-term care. Frailty is considered a key factor that contributes to a decline in quality of life among older adults (Figure 1).
Figure 1. Overview of frailty
Although there are various ways to assess frailty, one commonly used method is the "frailty phenotype" proposed by Fried. This scale consists of five criteria. Individuals who meet three or more of these criteria are classified as frail, while those who meet one or two are considered pre-frail--an early stage of frailty (Table).
Table. Evaluation criteria for frailty
● Metabolomics
Every day, countless chemical reactions take place in our bodies, producing small substances known as metabolites. These metabolites vary depending on factors such as our diet and overall physical condition.
Metabolomics is a cutting-edge field that involves using advanced technologies to comprehensively analyze a wide range of metabolites found in samples like blood or urine. In recent years, it has attracted growing attention for its potential to reveal changes in the human body associated with conditions such as illness or aging2,3).
In this study, we used a technique called gas chromatography-mass spectrometry (GC-MS) to identify approximately 500 different metabolites in the bloodstream.
Metabolomics allows us to observe subtle, invisible changes occurring in the body through a "chemical lens." Among its methods, GC-MS is known for its high reliability and is widely used in research related to food, health, and disease.
● Frailty-related metabolites
In this study, we compared blood samples from frail and robust older adults and identified seven metabolites that were found in lower amounts in those who were frail4) (Figure 2). Among these, we highlight four metabolites that were particularly noteworthy.
① Caffeine
Main sources: Found in coffee, green tea, black tea, and chocolate.
Role in the body: Caffeine stimulates the central nervous system, helping to reduce sleepiness and improve concentration. It has also been linked to reduced fatigue and enhanced athletic performance.
② Catechol (a metabolite of caffeine)
Main sources: Catechol is produced in the body when caffeine is broken down.
Role in the body: Among the substances generated during caffeine metabolism, catechol is known for its anti-oxidative properties and its ability to protect cells from oxidative stress.
③ Paraxanthine (a metabolite of caffeine)
Main sources: Paraxanthine is one of the main substances formed when caffeine is metabolized in the body.
Role in the body: Paraxanthine has stimulant effects and may promote lipid metabolism. It is also believed to contribute to improved physical performance.
④ Niacinamide (also known as nicotinamide, a form of vitamin B3)
Main sources: Found in foods such as meat, fish, mushrooms, and beans.
Role in the body: Niacinamide plays an essential role in energy metabolism, DNA repair, and has antioxidant effects. It is also important for maintaining healthy skin and a well-functioning nervous system.
These four metabolites are important substances that help maintain overall health. Notably, most of them are derived from what we eat. This means that our everyday diet and nutritional status can have a direct impact on our health and metabolism.
Looking ahead, it may be possible to help prevent frailty by maintaining a healthy balance of these metabolites. Our study provides valuable insight into how daily dietary habits are closely linked to our physical well-being.
Figure 2. Frailty-related metabolites
● Conclusion and Future Directions
In this study, we explored how metabolites in the bloodstream differ between frail and robust older adults. Notably, substances closely related to daily diet and nutrition--such as caffeine, its metabolites, and vitamin B3 (niacinamide)--were found in significantly different amounts between the two groups. These findings support the idea that our everyday dietary and lifestyle habits can have a meaningful impact on our health as we age.
Looking ahead, we aim to develop dietary improvement programs and establish specific nutritional guidelines to help "build bodies that are resistant to frailty." This will involve a deeper investigation into how the metabolites identified in this study are linked to frailty.
Ultimately, a well-rounded approach that considers not only medical care but also nutrition, physical activity, and social engagement is essential to support older adults in leading fulfilling lives--both physically and mentally. We hope that the insights from this study will contribute to achieving this goal. We also plan to continue sharing our research findings to support the health and well-being of older residents in Tokyo, as well as older adults and their families across Japan.
References
