An integrative machine-learning meta-analysis of high-throughput omics data identifies age-specific hallmarks of Alzheimer’s disease DOI Creative Commons
Maxim N. Shokhirev, Adiv A. Johnson

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 81, P. 101721 - 101721

Published: Aug. 25, 2022

Alzheimer's disease (AD) is an incredibly complex and presently incurable age-related brain disorder. To better understand this debilitating disease, we collated performed a meta-analysis on publicly available RNA-Seq, microarray, proteomics, microRNA samples derived from AD patients non-AD controls. 4089 originating tissues blood remained after applying quality filters. Since progression in correlates with age, stratified large dataset into three different age groups: < 75 years, 75-84 ≥ 85 years. The proteomics datasets were then combined integrated datasets. Ensemble machine learning was employed to identify genes proteins that can accurately classify as either or control. These predictive inputs subjected network-based enrichment analyses. ability of genes/proteins associated pathways the Molecular Signatures Database diagnose also tested. We separately identified microRNAs be used make diagnosis predicted gene targets most analysis. following key themes emerged our bioinformatics analyses: cell death, cellular senescence, energy metabolism, genomic integrity, glia, immune system, metal ion homeostasis, oxidative stress, proteostasis, synaptic function. Many results demonstrated unique age-specificity. For example, terms highlighting senescence only earliest intermediate ranges while majority relevant death appeared youngest patients. Existing literature corroborates importance these hallmarks AD.

Language: Английский

The Role of GDF15 as a Myomitokine DOI Creative Commons
Kornelia Johann, Maximilian Kleinert, Susanne Klaus

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 2990 - 2990

Published: Nov. 3, 2021

Growth differentiation factor 15 (GDF15) is a cytokine best known for affecting systemic energy metabolism through its anorectic action. GDF15 expression and secretion from various organs tissues induced in different physiological pathophysiological states, often linked to mitochondrial stress, leading highly variable circulating levels. In skeletal muscle the heart, basal of very low compared other organs, but can be stress conditions, such as intense exercise acute myocardial infarction, respectively. thus considered myokine cardiokine. GFRAL, exclusive receptor GDF15, expressed hindbrain neurons activation GDF15-GFRAL pathway an increased sympathetic outflow possibly hypothalamic-pituitary-adrenal (HPA) axis. There also evidence peripheral, direct effects on adipose tissue lipolysis possible autocrine cardiac effects. Metabolic behavioral outcomes signaling beneficial or detrimental, likely depending magnitude duration signal. This especially apparent production muscle, which both by disease states sarcopenia myopathy.

Language: Английский

Citations

82
Cancer Treatment-Induced Accelerated Aging in Cancer Survivors: Biology and Assessment DOI Open Access
Shuo Wang, Anna E. Prizment, Bharat Thyagarajan

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(3), P. 427 - 427

Published: Jan. 23, 2021

Rapid improvements in cancer survival led to the realization that many modalities used treat or control may cause accelerated aging survivors. Clinically, “accelerated aging” phenotypes survivors include secondary cancers, frailty, chronic organ dysfunction, and cognitive impairment, all of which can impact long-term health quality life The treatment-induced could be explained by telomere attrition, cellular senescence, stem cell exhaustion, DNA damage, epigenetic alterations. Several clocks biomarkers have been proposed potentially useful estimating biological age, provide specific information about how old an individual is biologically independent chronological age. Measuring age important for two reasons. First, it better predict risk treatment-related comorbidities than Second, additional value evaluating effects treatments personalizing therapies maximize efficacy treatment. A deeper understanding individuals with lead novel strategies reduce improve

Language: Английский

Citations

80
Promising biomarkers of human aging: In search of a multi-omics panel to understand the aging process from a multidimensional perspective DOI
Nadia Alejandra Rivero-Segura, Omar Yaxmehen Bello‐Chavolla, Oscar Salvador Barrera-Vázquez

et al.

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 64, P. 101164 - 101164

Published: Sept. 23, 2020

Language: Английский

Citations

75
Epigenetic aging: Biological age prediction and informing a mechanistic theory of aging DOI
Adam Li, Zane Koch, Trey Ideker

et al.

Journal of Internal Medicine, Journal Year: 2022, Volume and Issue: 292(5), P. 733 - 744

Published: June 20, 2022

Abstract Numerous studies have shown that epigenetic age—an individual's degree of aging based on patterns DNA methylation—can be computed and is associated with an array factors including diet, lifestyle, genetics, disease. One can expect still further associations will emerge additional research, but to what end? Prediction age was important first step, but—in our view—the focus must shift from chasing increasingly accurate computations understanding the links between epigenome mechanisms physiological changes aging. Here, we outline emerging areas research prioritize biological clinical application. First, survey recent progress in clocks, which are beginning predict not only chronological outcomes such as all‐cause mortality onset disease, or integrate signals across multiple processes. Second, discuss exemplifies how investigation building a mechanistic theory informing practice. Such examples include identifying methylation sites genes most strongly predictive aging—a subset strong potential biomarkers neurodegenerative disease cancer; relating clock predictions hallmarks aging; using longitudinal characterize human resulting discovery indications type 1 diabetes propensity for psychotic experiences.

Language: Английский

Citations

66
The multifactorial nature of healthy brain ageing: Brain changes, functional decline and protective factors DOI
Sonia Turrini, Bonnie Wong, Mark C. Eldaief

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 88, P. 101939 - 101939

Published: April 27, 2023

Language: Английский

Citations

37
Biomarkers of ageing: Current state‐of‐art, challenges, and opportunities DOI Creative Commons

Ruiye Chen,

Yueye Wang,

Shiran Zhang

et al.

MedComm – Future Medicine, Journal Year: 2023, Volume and Issue: 2(2)

Published: June 1, 2023

Abstract Given the unprecedented phenomenon of population ageing, studies have increasing captured heterogeneity within ageing process. In this context, concept “biological age” has been introduced as an integrated measure reflecting individualized pace. Identifying reliable and robust biomarkers age is critical for accurate risk stratification individuals exploration into antiageing interventions. Numerous potential proposed, spanning from molecular changes imaging characteristics to clinical phenotypes. review, we will start off with a discussion development biomarkers, then provide comprehensive summary currently identified in humans, discuss rationale behind each biomarker highlight their accuracy value contemporary perspective. Additionally, challenges, applications, future opportunities field. While research on led significant progress further investigations are still necessary. We anticipate that breakthroughs field involve exploring mechanisms, developing by combining various data sources or employing new technologies, validating existing emerging through collaboration longitudinal studies.

Language: Английский

Citations

26
ATAC-clock: An aging clock based on chromatin accessibility DOI Creative Commons
Francesco Morandini, Cheyenne Rechsteiner, Kevin Pérez

et al.

GeroScience, Journal Year: 2023, Volume and Issue: 46(2), P. 1789 - 1806

Published: Nov. 4, 2023

The establishment of aging clocks highlighted the strong link between changes in DNA methylation and aging. Yet, it is not known if other epigenetic features could be used to predict age accurately. Furthermore, previous studies have observed a lack effect age-related on gene expression, putting interpretability methylation-based into question. In this study, we explore use chromatin accessibility construct clocks. We collected blood from 159 human donors generated accessibility, transcriptomic, cell composition data. investigated how during constructed novel clock with median absolute error 5.27 years. by were strongly related transcriptomic alterations, aiding interpretation. additionally show that our performs significantly better than trained matched samples. conclusion, demonstrate relies cell-intrinsic alterations rather composition. Further, present new approach based which bear direct transcriptional but allow for more accurate predictions

Language: Английский

Citations

25
Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation DOI Creative Commons
Wayne Mitchell, Ludger J.E. Goeminne, Alexander Tyshkovskiy

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: March 22, 2024

Partial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset many diseases aging. However, delivery transgenes potential risk teratoma formation present challenges in vivo applications. Recent advances include use cocktails compounds reprogram somatic cells, but characteristics mechanisms partial cellular chemicals remain unclear. Here, we report a multi-omics characterization chemical fibroblasts from young aged mice. We measured effects on epigenome, transcriptome, proteome, phosphoproteome, metabolome. At phosphoproteome levels, saw widescale changes induced this treatment, with most notable signature being an upregulation mitochondrial oxidative phosphorylation. Furthermore, at metabolome level, observed reduction accumulation aging-related metabolites. Using both transcriptomic epigenetic clock-based analyses, show that reduces biological age mouse fibroblasts. demonstrate these have functional impacts, as evidenced respiration membrane potential. Taken together, results illuminate reagents rejuvenate systems warrant further investigation into adapting approaches reversal.

Language: Английский

Citations

13
Organ-specific biological clocks: Ageotyping for personalized anti-aging medicine DOI Creative Commons
Francesco Prattichizzo, Chiara Frigé, Valeria Pellegrini

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102253 - 102253

Published: March 4, 2024

Aging is a complex multidimensional, progressive remodeling process affecting multiple organ systems. While many studies have focused on studying aging across organs, assessment of the contribution individual organs to overall processes cutting-edge issue. An organ's biological age might influence other revealing multiorgan network. Recent data demonstrated similar yet asynchronous inter-organs and inter-individuals progression aging, thereby providing foundation track sources declining health in old age. The integration omics with common clinical parameters through artificial intelligence has allowed building organ-specific clocks, which can predict development specific age-related diseases at high resolution. peculiar aging-trajectory, referred as ageotype, provide novel tool for personalized anti-aging, preventive medicine. Here, we review relative clocks omics-based data, suggesting different rates. Additional research longitudinal including young subjects analyzing sex-related differences, should be encouraged apply ageotyping analysis purposes practice.

Language: Английский

Citations

12
Blood mitochondrial health markers cf-mtDNA and GDF15 in human aging DOI Creative Commons
Caroline Trumpff,

Qiuhan Huang,

Jeremy Michelson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Abstract Altered mitochondria biology can accelerate biological aging, but scalable biomarkers of mitochondrial health for population studies are lacking. We examined two potential candidates: 1) cell-free DNA (cf-mtDNA), a marker signaling elevated with disease states accessible as distinct entities from plasma or serum; and 2) growth differentiation factor 15 (GDF15), an established biomarker aging downstream energy transformation defects stress signaling. In cohort 430 participants aged 24-84 (54.2% women), we measured serum cf-mtDNA, GDF15 levels at timepoints 5 years apart, then assessed their associations age, BMI, diabetes, sex, health-related behaviors, psychosocial factors. As expected, showed positive, exponential association age (r=0.66, p<0.0001) increased by 33% over five years. cf-mtDNA was not correlated age. BMI sex were also related to nor GDF15. Type 2 diabetes only positively associated Exploring drivers systemic signaling, report novel linking higher education lower age-adjusted (r=-0.14, p<0.0034), both baseline the 5-year follow up, highlighting influence factors on health. Overall, our findings among adults spanning six decades lifespan establish between GDF15, emerging Further needed determine if blood metabolic be moderated behaviors.

Language: Английский

Citations

1