Epigenetic ageing clocks: statistical methods and emerging computational challenges

Nature Reviews Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Язык: Английский

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Proteomic aging clock (PAC) predicts age‐related outcomes in middle‐aged and older adults

Aging Cell, Год журнала: 2024, Номер 23(8)

Опубликована: Май 15, 2024

Abstract Beyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features biological might, therefore, offer useful information for the testing and, ultimately, clinical use gerotherapeutics. We aimed to develop a proteomic clock (PAC) all‐cause mortality risk as proxy age. Data were from UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 70 years 2923 plasma proteins assessed using Olink Explore 3072 assay®. 10.9% died during mean follow‐up 13.3 years, with age at death 70.1 years. The Spearman correlation PAC chronological was 0.77. showed robust age‐adjusted associations predictions onset various diseases in general disease‐free participants. associated deviation enriched several processes related hallmarks aging. Our results expand previous findings by showing that acceleration, based on PAC, strongly predicts incident disease outcomes. Particularly, it facilitates evaluation multiple conditions population, thereby, contributing prevention initial diseases, which vary among individuals may subsequently lead additional comorbidities.

Язык: Английский

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Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems

Cell Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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The Association between Proteomic Aging Clocks and the Risk of Cancer in Midlife Individuals

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

To measure the aging process before a cancer diagnosis, we developed first cancer-specific proteomic clock (CaPAC) and examined its association with risk in Atherosclerosis Risk Communities (ARIC) Multi-Ethnic Study of (MESA) studies. Using SomaScan assay, ARIC measured 4,712 proteins plasma samples collected 1990-92 from 3,347 participants who over follow-up until 2015 7,487 remained cancer-free, all aged 46-70. We constructed CaPAC0 using elastic net regression among two-thirds randomly selected cancer-free (N=4,991, training set) calculated age acceleration for (CaPAA0) as residuals on chronological remaining participants. used multivariable-adjusted Cox proportional hazards to calculate hazard ratios (HRs) overall, obesity-related, smoking-related, most common cancers (prostate, lung, breast, colorectal) CaPAA0 case-cohort design. replicated analysis 3,893 MESA 46-70 at Exam 1 (456 incident cancer). was correlated (r=0.82 0.86, respectively). In both MESA, significantly (p<0.05) associated overall [HRs per 5-years=1.08 1.23, respectively], smoking-related [HRs=1.30 1.54, lung [HRs=1.54 1.94, respectively]. also colorectal [HR=1.31], but not MESA. or prostate cancers. several types strongest observed risk.

Язык: Английский

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Geroscience in heart failure: the search for therapeutic targets in the shared pathobiology of human aging and heart failure

The Journal of Cardiovascular Aging, Год журнала: 2025, Номер 5(1)

Опубликована: Янв. 15, 2025

Age is a major risk factor for heart failure, but one that has been historically viewed as non-modifiable. Emerging evidence suggests the biology of aging malleable, and can potentially be intervened upon to treat age-associated chronic diseases, such failure. While represents new frontier therapeutic target discovery in challenges translating Geroscience research clinic are multifold. In this review, we propose strategy prioritizes initial human biology. We review rationale starting with omics, which generated important insights into shared (patho)biology then discuss how knowledge leveraged identify mechanisms most relevant Lastly, provide examples human-first approach, when paired rigorous functional assessments preclinical models, leading early-stage clinical development gerotherapeutic approaches

Язык: Английский

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Proteomic Markers of Aging and Longevity: A Systematic Review

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12634 - 12634

Опубликована: Ноя. 25, 2024

This article provides a systematic review of research conducted on the proteomic composition blood as part complex biological age estimation. We performed comprehensive analysis 17 publicly available datasets and compiled an integral list proteins. These proteins were sorted based their detection probability using mass spectrometry in human plasma. propose this basis for creating panel peptides quantifying content selected format aging clock. The are especially notable roles inflammatory processes lipid metabolism. Our findings suggest, first time, that associated with systemic disorders, including those approved by FDA clinical use, could serve potential markers aging.

Язык: Английский

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A plasma protein-based risk score to predict hip fractures

Nature Aging, Год журнала: 2024, Номер 4(8), С. 1064 - 1075

Опубликована: Май 27, 2024

Abstract As there are effective treatments to reduce hip fractures, identification of patients at high risk fracture is important inform efficient intervention strategies. To obtain a new tool for prediction, we developed protein-based score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The predicted incident fractures and improved discrimination two Trøndelag validation cohorts same When transferred antibody-based platform UK Biobank cohort, was strongly associated with (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53–1.77). score, but not available polygenic scores or bone mineral density, C-index beyond assessment (FRAX), which integrates information from clinical factors (C-index, FRAX 0.735 versus + 0.776). constitutes stratifying according risk; however, its improvement modest utility on femoral neck density remains be determined.

Язык: Английский

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Estimation of physiological aging based on routine clinical biomarkers: a prospective cohort study in elderly Chinese and the UK Biobank

BMC Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Ноя. 22, 2024

Chronological age (CA) does not reflect individual variation in the aging process. However, existing biological predictors are mostly based on European populations and overlook widespread nonlinear effects of clinical biomarkers. Using data from prospective Dongfeng-Tongji (DFTJ) cohort elderly Chinese, we propose a physiological index (PAI) 36 routine biomarkers to measure progress. We first determined optimal level each biomarker by restricted cubic spline Cox models. For with U-shaped relationship mortality, derived new variables model their distinct below above levels. defined PAI as weighted sum predictive mortality selected LASSO model. To acceleration, ΔPAI residual after regressing CA. evaluated value cardiovascular diseases (CVD) DFTJ cohort, well nine major chronic UK Biobank (UKB). In training set (n = 12,769, median follow-up: 10.38 years), identified 25 significant associations which 11 showed insignificant linear associations. By incorporating effects, CA 17 calculate PAI. testing 15,904, 5.87 predict concordance (C-index) 0.816 (95% confidence interval, [0.796, 0.837]), better than (C-index 0.771 [0.755, 0.788]) PhenoAge (0.799 [0.784, 0.814]). was incident CVD its subtypes, independent traditional risk factors. external validation UKB 296,931, 12.80 achieved C-index 0.749 (0.746, 0.752) remaining (0.706 [0.702, 0.709]) (0.743 [0.739, 0.746]). both UKB, calibrated when comparing predicted observed survival probabilities. Furthermore, outperformed any single risks eight age-related diseases. Our results highlight potential integrative evaluate acceleration facilitate development targeted intervention strategies for healthy aging.

Язык: Английский

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Menopause Hormone Replacement Therapy and Lifestyle Factors affect Metabolism and Immune System in the Serum Proteome of Aging Individuals

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 23, 2024

Abstract Aging is a fundamental risk factor for wide array of diseases. The Berlin Study II (BASE-II) cohort study designed to investigate the physical, mental, and social determinants successful aging. We utilized high-throughput mass spectrometry measure proteomes 1890 BASE-II participants, divided into two age groups: 27-37 years 60-85 years. employed multiple linear regression analyses explore effects demographic factors such as age, sex, BMI, along with hormonal treatments lifestyle factors, on serum proteome. identify new associations confirm previously described proteins linked BMI contraceptive use (HCU). Notably, we observed that abundance nutrient transport proteins, particularly apolipoproteins, metabolic diseases in aged individuals, including syndrome type 2 diabetes. Additionally, identified specific alterations explained by smoking alcohol consumption. further report significant proteome signature female participants corresponding menopause hormone replacement therapy (MHT). successfully classified these based MHT status an AUROC 0.82 using Complement Component 9 Plasminogen, slightly outperforming estradiol (AUROC: 0.80), active ingredient most preparations. Overall, our underscores impact therapies during aging, primarily affecting components immune system metabolism.

Язык: Английский

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A proteomic signature of healthspan

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 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.

Язык: Английский

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