As populations age, scientists are looking more closely at a hidden biological process that may help explain why some older adults remain mobile and independent while others experience a rapid decline in strength, balance, and endurance. A systematic review by A. Boshnjaku, R. Obërtinca, M. Hoxha, and colleagues examines whether five inflammation-related biomarkers—CRP, high-sensitivity CRP, interleukin-6, interleukin-10, and tumor necrosis factor-alpha—are linked to physical performance in older adults living in the community. Published in BMC Geriatrics, the review focuses on a question with major implications for healthy aging: can signals circulating in the blood reveal who is at greater risk of losing physical function?

The study centers on chronic, low-grade inflammation, a biological condition often associated with aging and commonly described as “inflammaging.” Unlike the intense inflammation triggered by an infection or injury, inflammaging can persist quietly over years. It may be influenced by immune-system changes, excess body fat, physical inactivity, chronic disease, and cellular stress. Although inflammation is essential for repairing tissue and fighting pathogens, prolonged activation can affect muscle metabolism, blood-vessel function, nervous-system signaling, and energy production. These changes could, in theory, make everyday movements such as walking, rising from a chair, or climbing stairs increasingly difficult.

C-reactive protein, or CRP, is one of the most widely used indicators of systemic inflammation. It is produced primarily by the liver in response to inflammatory signals, especially interleukin-6. Standard CRP testing is useful for detecting relatively pronounced inflammatory activity, while high-sensitivity CRP, known as hs-CRP, can measure much lower concentrations. That distinction matters in research on older adults, where subtle inflammatory differences may exist even when there is no obvious acute illness. However, neither CRP nor hs-CRP identifies a single disease or proves that inflammation itself caused a decline in physical ability.

The review also considers three signaling proteins known as cytokines. Interleukin-6, or IL-6, can promote inflammation but also participates in muscle adaptation and energy regulation, making its effects highly dependent on timing, tissue, and physiological context. Tumor necrosis factor-alpha, or TNF-α, is a potent inflammatory mediator that can influence muscle protein breakdown and interfere with insulin signaling. Interleukin-10, or IL-10, generally acts as an anti-inflammatory regulator, helping restrain excessive immune activation. Examining these markers together offers a more nuanced picture than relying on a single laboratory value.

Physical performance is a crucial measure of aging because it reflects how effectively multiple systems work together. Muscle strength alone does not determine whether a person can remain independent. Walking speed, repeated chair stands, balance, grip strength, endurance, and composite tests such as the Short Physical Performance Battery can reveal the combined effects of the muscular, cardiovascular, neurological, and skeletal systems. For people living outside hospitals and care facilities, these measures may also provide a practical snapshot of resilience in everyday life. A small difference in performance can translate into a major difference in fall risk, mobility, and the ability to manage daily activities.

By bringing together evidence from studies of community-dwelling older adults, the authors address an important gap between laboratory research and real-world aging. Older people living independently are not a uniform group: some have multiple chronic conditions, while others remain highly active; some take anti-inflammatory medications, and others do not. Diet, smoking, obesity, socioeconomic conditions, sleep, recent infections, and exercise can all alter cytokine levels and physical performance. A systematic review can help determine whether associations between biomarkers and function appear consistently across this complex population or whether they vary substantially from one study to another.

The review’s importance lies not only in asking whether inflammatory markers are associated with poorer performance, but also in highlighting the limitations of interpreting such relationships. A high biomarker level may be a consequence of frailty, reduced activity, obesity, or an undiagnosed illness rather than the original cause of decline. Conversely, a single blood sample may fail to capture fluctuations in inflammation over time. Differences in laboratory methods, cutoff values, participant health, medication use, and performance tests can make studies difficult to compare. These issues are central when translating population-level associations into decisions about an individual patient.

The findings may ultimately support a broader approach to healthy aging in which inflammation is considered alongside strength, nutrition, cardiovascular health, cognition, and social environment. The biomarkers discussed in the review are not presented as standalone tests that can predict the future with certainty. Instead, they may help researchers understand why physical function changes and identify biological pathways that could be targeted through exercise, weight management, treatment of chronic disease, or other interventions. The study also underscores the need for longitudinal research capable of separating cause from consequence and for standardized testing that can connect laboratory signals with meaningful improvements in daily life.

For now, the review places a spotlight on the immune system as a possible contributor to the physical changes associated with later life. Its focus on CRP, hs-CRP, IL-6, IL-10, and TNF-α reflects the growing recognition that aging is not simply the result of muscles becoming weaker, but of interconnected changes across the body. Understanding how these inflammatory signals relate to mobility could help scientists develop more precise strategies for preserving independence—while reminding clinicians and the public that a blood test is most informative when interpreted together with a person’s functional ability, medical history, and lived environment.

Subject of Research: The relationship between inflammatory biomarkers and physical performance in community-dwelling older adults.

Article Title: What is the impact of CRP, hs-CRP, IL-6, IL-10, and TNFα in physical performance in community-dwelling older adults: a systematic review.

Article References: Boshnjaku, A., Obërtinca, R., Hoxha, M. et al. What is the impact of CRP, hs-CRP, IL-6, IL-10, and TNFα in physical performance in community-dwelling older adults: a systematic review. BMC Geriatrics (2026). https://doi.org/10.1186/s12877-026-08080-8

Image Credits: AI Generated

DOI: 10.1186/s12877-026-08080-8

Keywords: aging, older adults, inflammation, CRP, hs-CRP, IL-6, IL-10, TNF-α, physical performance, inflammaging, systematic review

Alzheimer’s disease may be leaving a more precise anatomical signature in the brain than scientists once realized. A new study published in Translational Psychiatry investigates regional changes in the fine structure of brain tissue immediately beneath the cerebral cortex, known as the juxtacortical region, and links those changes to patterns of gene expression associated with neurodegeneration. The work, led by J. Zhang, L. Sun, X. Yang and colleagues, offers a combined view of Alzheimer’s biology that connects what can be detected through brain imaging with the molecular programs active inside vulnerable neural tissue.

The juxtacortical zone is a narrow but biologically important interface. It lies directly beneath the cortex, the outer layer responsible for functions including memory, language, perception and decision-making. Although much Alzheimer’s research has focused on cortical thinning, large-scale tissue loss and abnormalities in deeper brain structures, the tissue bordering the cortex may reveal earlier or more regionally specific changes. Its organization includes densely packed axons, dendrites, neurons, glial cells and blood vessels, all of which can be affected as the disease progresses. Subtle disruption in this area could therefore provide clues before dramatic anatomical damage becomes visible.

The study’s central idea is that Alzheimer’s disease does not alter every brain region in the same way. Instead, neurodegeneration follows a complex geography shaped by cellular composition, connectivity, metabolism and genetic vulnerability. By examining regional juxtacortical microstructural changes, the researchers seek to move beyond a simple question of whether tissue has shrunk. Microstructure refers to the organization of brain components at scales smaller than conventional anatomical imaging can directly resolve. Variations in water diffusion, tissue organization and local architecture can serve as indirect markers of changes to axons, membranes, extracellular space and other microscopic features.

This regional perspective matters because the same imaging signal can arise from different biological processes. A change in tissue organization may reflect loss of neuronal connections, damage to myelinated fibers, altered glial activity, inflammation or shifts in the balance of cellular compartments. Imaging alone can reveal where abnormalities are concentrated, but it cannot always explain why they occur. The researchers therefore paired their investigation of juxtacortical structure with gene-expression information, creating a bridge between regional anatomy and molecular biology. That combination can help identify which biological pathways may underlie the imaging patterns seen in Alzheimer’s disease.

Gene expression describes the activity of genes within cells and tissues: which genetic instructions are being read, and at what levels. In the Alzheimer’s brain, these molecular signatures can point toward processes such as synaptic dysfunction, immune activation, impaired energy production, protein handling and cellular stress. Mapping gene-expression patterns onto regions showing microstructural alterations may reveal whether vulnerable areas share particular molecular characteristics. It may also help distinguish tissue changes related directly to neurodegeneration from those associated with aging or general brain atrophy. The result is a more layered portrait of disease, linking microscopic organization to the biological machinery that maintains it.

The findings described by the paper’s title suggest that these two forms of evidence—regional microstructure and gene activity—provide complementary insights into Alzheimer’s pathology. Rather than treating the brain as a uniform organ undergoing gradual damage, the research emphasizes a mosaic of vulnerability. Some areas may show distinctive structural disruption alongside gene-expression profiles associated with neuronal injury or altered support-cell function, while other regions may be relatively resilient. Such differences could help explain why symptoms vary between individuals and why memory, language, attention and other abilities can deteriorate along different trajectories.

The work could also influence how scientists think about biomarkers. A biomarker is a measurable biological feature that helps indicate disease presence, progression or response to treatment. Traditional markers of Alzheimer’s include abnormal amyloid and tau proteins, brain volume loss and changes in metabolism. Juxtacortical microstructural measures, especially when interpreted alongside molecular data, could eventually add regional detail to this toolkit. They might help researchers identify tissue at risk, track the spread of degeneration or evaluate whether an experimental therapy is protecting neural architecture even before clinical improvement becomes obvious.

However, the study should not be interpreted as proof that a single imaging signature can diagnose Alzheimer’s disease or predict an individual’s future with certainty. Microstructural measurements are indirect, and gene-expression data often come from specialized datasets that may not capture every cell type or every stage of disease. Differences in age, disease severity, medication, vascular health and individual brain organization can also influence results. The strength of the approach lies not in one isolated measurement, but in the convergence of regional imaging and molecular evidence. Together, these methods can generate testable hypotheses about how and where neurodegeneration unfolds.

The broader message is that Alzheimer’s research is moving toward increasingly integrated maps of the human brain. The study by Zhang, Sun, Yang and colleagues presents the juxtacortical region as a potentially informative frontier, where microscopic tissue organization and gene regulation intersect. If future research confirms these relationships in larger and more diverse groups, the approach could sharpen disease staging and improve the design of targeted therapies. For now, the findings add weight to a crucial principle in neuroscience: understanding Alzheimer’s requires knowing not only which brain regions are damaged, but also how their cellular architecture and molecular identity make them vulnerable.

Subject of Research: Regional juxtacortical microstructural changes and gene expression in Alzheimer’s disease

Article Title: Regional juxtacortical microstructural changes and gene expression provide insights into neurodegeneration in Alzheimer’s disease

Article References: Zhang, J., Sun, L., Yang, X. et al. “Regional juxtacortical microstructural changes and gene expression provide insights into neurodegeneration in Alzheimer’s disease.” Translational Psychiatry (2026). https://doi.org/10.1038/s41398-026-04292-z

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41398-026-04292-z

Keywords: Alzheimer’s disease, neurodegeneration, juxtacortical microstructure, gene expression, brain imaging, neuroscience, biomarkers, translational psychiatry