A groundbreaking new study published in the prestigious journal Nature Communications reveals that blood protein levels undergo significant transformations throughout childhood and adolescence, and that these changes differ notably between females and males as they age. This research, conducted by scientists at Karolinska Institutet in collaboration with SciLifeLab and KTH Royal Institute of Technology, challenges the long-standing reliance on adult reference values for interpreting blood protein biomarkers in younger populations. Their findings suggest that using adult norms to assess protein levels in children and adolescents may lead to misinterpretations, as protein expression dynamically evolves throughout early life stages.
The investigation followed a cohort of 100 individuals drawn from the population-based BAMSE study, collecting blood samples at four critical ages: 4, 8, 16, and 24 years. Utilizing cutting-edge proteomic technology, researchers quantified over 5,000 proteins in these samples, with longitudinal tracking possible for approximately 3,500 proteins. Astonishingly, more than half of these proteins displayed significant age-dependent fluctuations, emphasizing that protein composition in blood is continuously remodeled even in the earliest years of life.
Of particular interest were the pronounced alterations occurring between ages 8 and 16, which coincide with the onset and progression of puberty. During this phase, many proteins exhibit sharp increases in concentration, followed by subsequent declines as individuals transition into early adulthood. Other proteins demonstrated more gradual linear trends, either increasing or decreasing steadily from childhood through to adulthood. These dynamic patterns highlight puberty as a pivotal biological window during which systemic protein architecture is extensively reshaped.
Sophia Björkander, assistant professor and docent at Karolinska Institutet’s Department of Clinical Science and Education, and a lead author of the study, emphasized the biological complexity revealed: “Our results unequivocally demonstrate that adult protein reference intervals are inadequate for younger populations. The proteome is not static; it is deeply influenced by age-related developmental processes that start early in life.”
Adding an additional layer of complexity, the study uncovered distinct sex-specific differences in blood protein expression that intensify with age. Early childhood showed relatively few disparities between girls and boys; however, by the age of 24, nearly 30% of the surveyed proteins differed significantly between women and men. These differences spanned proteins involved in critical physiological systems such as growth regulation, metabolic pathways, immune responses, and reproductive functions, underscoring the necessity of sex-specific considerations in clinical diagnostics and biomarker development.
“As protein expression diverges distinctly between males and females post-puberty, it becomes imperative to factor in both age and gender when interpreting proteomic data,” said Björkander. This finding challenges the generalized application of biomarker thresholds and points to a future where personalized medicine accounts for biological sex and developmental stage to enhance diagnostic accuracy.
Blood proteins have long been utilized as pivotal biomarkers in medicine, employed to detect inflammation, hormonal imbalances, cardiovascular anomalies, and metabolic disorders. This study’s revelations, however, caution against simplistic interpretations of protein levels in pediatric and adolescent populations. What may appear as abnormal protein concentrations could simply reflect normative, age-appropriate physiological maturation rather than pathologic conditions.
Erik Melén, senior author and project leader at BAMSE, added insight on the translational potential of these findings: “By systematically mapping the protein landscape as it evolves from childhood into early adulthood, we establish a dynamic reference framework. This enables earlier identification of deviations from typical development and opens avenues for improved risk stratification of chronic diseases and tailoring of individualized therapeutic interventions.”
Despite the robust technological methodology and longitudinal design, the authors acknowledge certain limitations, including the relatively small sample size and demographic homogeneity of the cohort, which may affect generalizability. Further research involving larger and more diverse populations will be essential to validate and expand these initial findings.
This study is an integral part of the Human Disease Blood Atlas, an ambitious project within the Human Protein Atlas initiative, which aims to chart comprehensive blood protein profiles across varied demographics. The BAMSE cohort itself is a longstanding Swedish birth cohort study dedicated to elucidating environmental and genetic influences on health, jointly administered by Karolinska Institutet and the Stockholm region’s environmental medical centers.
Funding for this research was provided by several prestigious agencies, including the Swedish Research Council, Region Stockholm, the Swedish Heart-Lung Foundation, and the Knut and Alice Wallenberg Foundation. The authors report no conflicts of interest, underscoring the impartiality of the study.
This transformative research presents paradigm-shifting evidence that blood proteomics is a highly dynamic, age- and sex-dependent biological system. It calls for a revision of current clinical standards and beckons the development of adaptive biomarker reference databases that reflect the biological realities of growth and development. By enhancing our understanding of the proteomic trajectories from childhood to adulthood, this work sets the stage for innovation in pediatric diagnostics, precision medicine, and ultimately, improved health outcomes across the lifespan.
Subject of Research: Longitudinal changes in blood protein levels from childhood through early adulthood, with emphasis on age and sex differences in proteomic profiles.
Article Title: Longitudinal protein profiling of blood during childhood into early adulthood
News Publication Date: 22-Apr-2026
Web References: https://doi.org/10.1038/s41467-026-72095-3
Image Credits: Photo by Karolinska Institutet, featuring Sophia Björkander
Keywords
Blood, Biomarkers, Proteomics, Childhood Development, Adolescence, Sex Differences, Puberty, Personalized Medicine, Protein Profiling, Human Protein Atlas, BAMSE Cohort, Clinical Diagnostics
Tags: age-dependent protein fluctuationsage-specific reference values for blood proteinsBAMSE cohort proteomic analysisblood protein level changes in childhoodchildhood to adulthood protein dynamicsKarolinska Institutet blood protein researchlongitudinal blood proteomics studypediatric blood biomarker interpretationprotein biomarkers in adolescenceproteomics in developmental biologypuberty impact on blood proteinssex differences in blood protein expression
