ArticlePloS one2015
Detection of a novel, integrative aging process suggests complex physiological integration.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Shared biological pathways for frailty and cognitive impairment: A systematic review.Ageing research reviews · 2018Pooled it
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- Whole-body networks: a holistic approach for studying aging.GeroScience · 2025Article
- Association of C-reactive protein to albumin ratio with all-cause and cardiovascular mortality in patients with chronic kidney disease stages 3-5.Environmental health and preventive medicine · 2025Article
- Ratio of red blood cell distribution width to albumin level and risk of mortality in sarcopenic obesity.Scientific reports · 2024Article
- Red cell distribution width/albumin ratio as a marker for metabolic syndrome: findings from a cross-sectional study.BMC endocrine disorders · 2024Article
- Ratio of Red Blood Cell Distribution Width to Albumin Level and Risk of Mortality.JAMA network open · 2024Article
- Validation of biomarkers of aging.Nature medicine · 2024Review
- Progress in the study of aging marker criteria in human populations.Frontiers in public health · 2024Review
- Discordant Biological and Chronological Age: Implications for Cognitive Decline and Frailty.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Natural Animal Populations as Model Systems for Understanding Early Life Adversity Effects on Aging.Integrative and comparative biology · 2023Article
- Explainable machine learning framework to predict personalized physiological aging.Aging cell · 2023Article
- Efficient representations of binarized health deficit data: the frailty index and beyond.GeroScience · 2023Article
- Exploring Shared Effects of Multisensory Impairment, Physical Dysfunction, and Cognitive Impairment on Physical Activity: An Observational Study in a National Sample.Journal of aging and physical activity · 2022Observational
- A complex systems approach to aging biology.Nature aging · 2022Review
- Article
- Relationship between adiponectin and intramuscular fat content determined by ultrasonography in older adults.PloS one · 2022Article
- Feature Selection Algorithms Enhance the Accuracy of Frailty Indexes as Measures of Biological Age.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
- Cardiovascular risk and aging: the need for a more comprehensive understanding.Journal of geriatric cardiology : JGC · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Many studies of aging examine biomarkers one at a time, but complex systems theory and network theory suggest that interpretations of individual markers may be context-dependent. Here, we attempted to detect underlying processes governing the levels of many biomarkers simultaneously by applying principal components analysis to 43 common clinical biomarkers measured longitudinally in 3694 humans from three longitudinal cohort studies on two continents (Women's Health and Aging I & II, InCHIANTI, and the Baltimore Longitudinal Study on Aging). The first axis was associated with anemia, inflammation, and low levels of calcium and albumin. The axis structure was precisely reproduced in all three populations and in all demographic sub-populations (by sex, race, etc.); we call the process represented by the axis "integrated albunemia." Integrated albunemia increases and accelerates with age in all populations, and predicts mortality and frailty--but not chronic disease--even after controlling for age. This suggests a role in the aging process, though causality is not yet clear. Integrated albunemia behaves more stably across populations than its component biomarkers, and thus appears to represent a higher-order physiological process emerging from the structure of underlying regulatory networks. If this is correct, detection of this process has substantial implications for physiological organization more generally.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.