A compact protein panel for organ-specific age and chronic disease prediction DOI Creative Commons

А. А. Владимирова,

Ludger J.E. Goeminne, Alexander Tyshkovskiy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 15, 2024

Abstract Recent advances in plasma proteomics have led to a surge of computational models that accurately predict chronological age, mortality, and diseases from simple blood draw. We leverage the data ∼50,000 participants UK Biobank investigate predictive power such compared individual proteins metabolites by assessing disease risk organ aging. find that, with exception brain-related diseases, protein levels often match or surpass elaborate clocks trained on age mortality risk. Certain effectively multiple affecting specific organs. show most cases, better than polygenic scores, identify novel associations between human including LAMP3 COPD, CHHR2 liver disease, FAMC3 kidney TMED1 gout. present focused panel 21 biomarkers reveals health state six organs associated major age-related diseases. Our predicts common cirrhosis fibrosis, dementia, failure, type II diabetes established panels aging models. Through its vast coverage our compact offers cost-effective alternative full-scale proteomic analyses, making it prime candidate for non-invasive clinical detection management numerous simultaneously.

Language: Английский

Dietary Triterpenoids in Functional Food and Drug Ingredients: a review of structure-activity relationships, biosynthesis, applications, and AI-driven strategies DOI
Chao Fang, Haixia Yang, Daidi Fan

et al.

Trends in Food Science & Technology, Journal Year: 2025, Volume and Issue: unknown, P. 104961 - 104961

Published: March 1, 2025

Language: Английский

Citations

1
Compression of morbidity by interventions that steepen the survival curve DOI Creative Commons
Yifan Yang, Avi Mayo, Tomer Levy

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 8, 2025

Longevity research aims to extend the healthspan while minimizing duration of disability and morbidity, known as sickspan. Most longevity interventions in model organisms healthspan, but it is not whether they compress sickspan relative lifespan. Here, we present a theory that predicts which sickspan, based on shape survival curve. Interventions such caloric restriction mean lifespan preserving curve, are predicted proportionally, without compressing it. Conversely, subset steepen curve We explain this saturating-removal mathematical aging, evidence from longitudinal health data mice, Caenorhabditis elegans Drosophila melanogaster. apply identify potential for combinations interventions. This approach offers strategies morbidity extending healthspan.

Language: Английский

Citations

1
How to measure biological aging in humans DOI
Luigi Ferrucci, Nir Barzilai, Daniel W. Belsky

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

Citations

0
The Mitochondria‐Targeted Peptide Therapeutic Elamipretide Improves Cardiac and Skeletal Muscle Function During Aging Without Detectable Changes in Tissue Epigenetic or Transcriptomic Age DOI Creative Commons
Wayne Mitchell, Gavin Pharaoh, Alexander Tyshkovskiy

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

ABSTRACT Aging‐related decreases in cardiac and skeletal muscle function are strongly associated with various comorbidities. Elamipretide (ELAM), a novel mitochondria‐targeted peptide, has demonstrated broad therapeutic efficacy ameliorating disease conditions mitochondrial dysfunction across both clinical pre‐clinical models. Herein, we investigated the impact of 8‐week ELAM treatment on pre‐ post‐measures C57BL/6J mice frailty, muscle, function, coupled post‐treatment assessments biological age affected molecular pathways. We found that health status, as measured by frailty index, strain, diastolic force, is significantly diminished age, force changing sex‐dependent manner. Conversely, mitigated accumulation was able to partially reverse these declines, evidenced treatment‐induced increases strain fatigue resistance. Despite improvements, did not detect statistically significant changes gene expression or DNA methylation profiles indicative reorganization reduced most ELAM‐treated groups. However, pathway analyses revealed showed pro‐longevity shifts expression, such upregulation genes involved fatty acid metabolism, translation, oxidative phosphorylation, downregulation inflammation. Together, results indicate effective at mitigating signs sarcopenia an aging mouse model, but functional improvements occur independently detectable epigenetic transcriptomic age. Thus, some age‐related may be uncoupled from

Language: Английский

Citations

0
Integrative cross‐tissue analysis unveils complement‐immunoglobulin augmentation and dysbiosis‐related fatty acid metabolic remodeling during mammalian aging DOI Creative Commons
Feng Zhang,

Rong Li,

Yasong Liu

et al.

iMeta, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Abstract Aging‐related decline and adaptation are complex, multifaceted processes that affect various tissues increase risk of chronic diseases. To characterize key changes in cross‐tissue aging, we performed comprehensive proteomic metabolomic analyses across 21 solid plasma samples, alongside shotgun metagenomic profiling fecal microbial communities young aged mice. Our findings revealed widespread aging‐rewired inflammation, characterized by complement system activation universal immunoglobulins accumulation multiple tissues. This inflammatory remodeling significantly enhanced vulnerability to aging‐related tissue injury. Moreover, identified organ‐specific organ‐enriched proteins with high functional specificity. Among these, were closely linked disorders arising from lipid metabolism dysfunction. Analysis multi‐tissue profiles aging disrupted inter‐tissue metabolic coupling, activities polyunsaturated fatty acids metabolism, gut microbiota homeostasis. Aged mice exhibited a marked decrease Escherichia an Helicobacter , strongly correlating alterations omega‐3 omega‐6 acid abundances. Through multi‐omics integration, molecular hubs driving organismal responses aging. Collectively, our study uncovers extensive aging‐associated tissues, emphasizing the interplay between systemic inflammation dysbiosis‐driven remodeling. These provide deeper insights into development healthy perspective.

Language: Английский

Citations

0
Correlation of Accelerated Biological Aging with the Prevalence and Poor Prognosis of Early-Onset Lung Cancer: Insights from a Multicenter Case–Control Study and the UK Biobank DOI

Ruo-Lin Gao,

Yuxuan Liao, Qiwen Zheng

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
A proteomic signature of healthspan DOI Creative Commons
Chia‐Ling Kuo,

Peiran Liu,

Zhiduo Chen

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 26, 2024

The focus of aging research has shifted from increasing lifespan to enhancing healthspan reduce the time spent living with disability. Despite significant efforts develop biomarkers aging, few studies have focused on healthspan. We developed a proteomics-based signature (healthspan proteomic score (HPS)) using data UK Biobank Pharma Proteomics Project (53,018 individuals and 2920 proteins). A lower HPS was associated higher mortality risk several age-related conditions, such as COPD, diabetes, heart failure, cancer, myocardial infarction, dementia, stroke. showed superior predictive accuracy for these outcomes compared chronological age biological measures. Proteins were enriched in hallmark pathways immune response, inflammation, cellular signaling, metabolic regulation. Our findings demonstrate validity HPS, making it valuable tool assessing potential surrogate marker geroscience-guided studies.

Language: Английский

Citations

0
The mitochondrial-targeted peptide therapeutic elamipretide improves cardiac and skeletal muscle function during aging without detectable changes in tissue epigenetic or transcriptomic age DOI Creative Commons
Wayne Mitchell, Gavin Pharaoh, Alexander Tyshkovskiy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Aging-related decreases in cardiac and skeletal muscle function are strongly associated with various comorbidities. Elamipretide (ELAM), a novel mitochondrial-targeted peptide, has demonstrated broad therapeutic efficacy ameliorating disease conditions mitochondrial dysfunction across both clinical pre-clinical models. ELAM is proposed to restore bioenergetic by stabilizing inner membrane structure increasing oxidative phosphorylation coupling efficiency. Although treatment effectively attenuates physiological declines multiple tissues rodent aging models, it remains unclear whether these functional improvements correlate favorable changes molecular biomarkers of aging. Herein, we investigated the impact 8-week on pre- post- measures C57BL/6J mice frailty, muscle, function, coupled post-treatment assessments biological age affected pathways. We found that health status, as measured frailty index, strain, diastolic force significantly diminished age, changing sex-dependent manner. Conversely, mitigated accumulation was able partially reverse declines, evidenced treatment-induced increases strain fatigue resistance. Despite improvements, did not detect statistically significant gene expression or DNA methylation profiles indicative reorganization reduced most ELAM-treated groups. However, pathway analyses revealed showed pro-longevity shifts such upregulation genes involved fatty acid metabolism, translation phosphorylation, downregulation inflammation. Together, results indicate effective at mitigating signs sarcopenia heart failure an mouse model, but occur independently detectable epigenetic transcriptomic age. Thus, some age-related may be uncoupled from

Language: Английский

Citations

0
A compact protein panel for organ-specific age and chronic disease prediction DOI Creative Commons

А. А. Владимирова,

Ludger J.E. Goeminne, Alexander Tyshkovskiy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 15, 2024

Abstract Recent advances in plasma proteomics have led to a surge of computational models that accurately predict chronological age, mortality, and diseases from simple blood draw. We leverage the data ∼50,000 participants UK Biobank investigate predictive power such compared individual proteins metabolites by assessing disease risk organ aging. find that, with exception brain-related diseases, protein levels often match or surpass elaborate clocks trained on age mortality risk. Certain effectively multiple affecting specific organs. show most cases, better than polygenic scores, identify novel associations between human including LAMP3 COPD, CHHR2 liver disease, FAMC3 kidney TMED1 gout. present focused panel 21 biomarkers reveals health state six organs associated major age-related diseases. Our predicts common cirrhosis fibrosis, dementia, failure, type II diabetes established panels aging models. Through its vast coverage our compact offers cost-effective alternative full-scale proteomic analyses, making it prime candidate for non-invasive clinical detection management numerous simultaneously.

Language: Английский

Citations

0