Integrated Multi-Omics for Novel Aging Biomarkers and Antiaging Targets

Biomolecules, Год журнала: 2021, Номер 12(1), С. 39 - 39

Опубликована: Дек. 28, 2021

Aging is closely related to the occurrence of human diseases; however, its exact biological mechanism unclear. Advancements in high-throughput technology provide new opportunities for omics research understand pathological process various complex diseases. However, single-omics technologies only limited insights into mechanisms DNA, RNA, protein, metabolites, and microorganisms usually play complementary roles perform certain functions together. In this review, we summarize multi-omics methods based on most relevant biomarkers better molecular disease causes. The integration can systematically reveal interactions among aging molecules from a multidimensional perspective. Our review provides regarding discovery biomarkers, aging, identification novel antiaging targets. Overall, data genomics, transcriptomics, proteomics, metabolomics, integromics, microbiomics, systems biology contribute candidate targets interventions.

Язык: Английский

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A comprehensive AI‐driven analysis of large‐scale omic datasets reveals novel dual‐purpose targets for the treatment of cancer and aging

Aging Cell, Год журнала: 2023, Номер 22(12)

Опубликована: Окт. 27, 2023

Abstract As aging and tumorigenesis are tightly interconnected biological processes, targeting their common underlying driving pathways may induce dual‐purpose anti‐aging anti‐cancer effects. Our transcriptomic analyses of 16,740 healthy samples demonstrated tissue‐specific age‐associated gene expression, with most tumor suppressor genes downregulated during aging. Furthermore, a large‐scale pan‐cancer analysis 11 solid types (11,303 cases 4431 control samples) revealed that many cellular such as protein localization, DNA replication, repair, cell cycle, RNA metabolism, were upregulated in cancer but tissues, whereas regulating senescence both cancer. Common targets identified by the AI‐driven target discovery platform—PandaOmics. Age‐associated selected further classified into four groups based on reported roles lifespan. Among 51 experimental evidence, 22 proposed for treatment same therapeutic direction. without known lifespan‐regulating activity, 23 predicted properties. Knockdown histone demethylase KDM1A, one these unexplored candidates, significantly extended lifespan Caenorhabditis elegans . Given KDM1A's activities preclinical clinical studies, our findings propose KDM1A promising target. This is first study utilizing an innovative approach to identify candidates treatment, supporting value AI‐assisted identification drug discovery.

Язык: Английский

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Age or lifestyle-induced accumulation of genotoxicity is associated with a length-dependent decrease in gene expression

iScience, Год журнала: 2023, Номер 26(4), С. 106368 - 106368

Опубликована: Март 9, 2023

DNA damage has long been advocated as a molecular driver of aging. occurs in stochastic manner, and is therefore more likely to accumulate longer genes. The length-dependent accumulation transcription-blocking damage, unlike that somatic mutations, should be reflected gene expression datasets We analyzed function length several single-cell RNA sequencing mouse human found pervasive age-associated underexpression genes across species, tissues, cell types. Furthermore, we observed associated with UV-radiation smoke exposure, progeroid diseases, Cockayne syndrome, trichothiodystrophy. Finally, studied published sets showing global age-related changes. Genes underexpressed aging were significantly than overexpressed These data highlight previously undetected hallmark show genotoxicity could lead reduced polymerase II processivity.

Язык: Английский

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Demographic consequences of damage dynamics in single-cell aging

Physical Review Research, Год журнала: 2025, Номер 7(1)

Опубликована: Март 28, 2025

Aging is driven by damage accumulation leading to a decline in function over time. In single-cell systems, addition this within individuals, asymmetric partitioning at cell division can play crucial role shaping demographic aging patterns. Despite experimental studies that provide quantitative data the molecular and levels, integration of complementary theory explaining how cellular production propagate influence patterns still lacking. Here, we present generic flexible model using stochastic differential equation approach incorporates during divisions. We formulate an analytical approximation linking parameters along mother lineages. Interestingly, lifespan cells follows inverse Gaussian distribution, whose underlying properties derive from parameters. demonstrate stochasticity (noise) production, asymmetry partitioning, frequency shape distribution. Confronting with various empirical machine reveals nonexponential scaling mortality rates, cannot be captured classical Gompertz-Makeham models. Our findings deeper understanding fundamental processes contribute dynamics generate model's nature offers valuable framework for investigating diverse biological systems. Published American Physical Society 2025

Язык: Английский

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The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function

eLife, Год журнала: 2021, Номер 10

Опубликована: Апрель 20, 2021

Aging is accompanied by disrupted information flow, resulting from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders including skeletal muscle wasting, or sarcopenia. To derive a global metric growing ‘disorderliness’ aging muscle, we employed statistical physics approach estimate the state parameter, entropy, as function genes associated with hallmarks aging. Escalating network entropy reached an inflection point at old age, while structural and functional alterations progressed into oldest-old age. probe potential for restoration ‘order’ reversal sarcopenic phenotype, systemically overexpressed longevity protein, Klotho, via AAV. Klotho overexpression modulated representing all in mice, but pathway enrichment revealed directions changes were, many genes, age-dependent. Functional improvements were also improved strength failed induce benefits beyond entropic tipping point.

Язык: Английский

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Resilience integrates concepts in aging research

iScience, Год журнала: 2022, Номер 25(5), С. 104199 - 104199

Опубликована: Апрель 6, 2022

Aging research is unparalleled in the breadth of disciplines it encompasses, from evolutionary studies examining forces that shape aging to molecular uncovering underlying mechanisms age-related functional decline. Despite a common focus advance our understanding aging, these have proceeded along distinct paths with little cross-talk. We propose concept resilience can bridge this gap. Resilience describes ability system respond perturbations by returning its original state. Although has been applied few individual such as frailty and cognitive decline, not explored unifying conceptual framework able connect fields. argue because resilience-based cross broad physiological levels time scales provide missing links diverse disciplines. The resulting will facilitate predictive modeling validation influence targets directions on biology aging.

Язык: Английский

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Regulatory RNAs in immunosenescence

Immunity Inflammation and Disease, Год журнала: 2024, Номер 12(3)

Опубликована: Март 1, 2024

Abstract Background Immunosenescence is a multifactorial stress response to different intrinsic and extrinsic insults that cause immune deterioration accompanied by genomic or epigenomic perturbations. It now widely recognized genes proteins contributing in the process of immunosenescence are regulated various noncoding (nc) RNAs, including microRNAs (miRNAs), long ncRNAs, circular RNAs. Aims This review article aimed evaluate regulatore RNAs roles immunosenescence. Methods We analyzed publications were focusing on regulatory several aspects Results In setting, ncRNAs have been found play at both transcriptional post‐transcriptional levels. These factors cooperate regulate initiation gene expression programs sustaining senescence phenotype proinflammatory responses. Conclusion complex with pivotal alterations function occurring age. The extensive network drive immunosenescence‐related features mainly directed variety such as miRNAs, lncRNAs, circRNAs. Latest findings about regulation innate adaptive cells well their role pathways, provide better understanding

Язык: Английский

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Multi-omics approaches to human biological age estimation

Mechanisms of Ageing and Development, Год журнала: 2019, Номер 185, С. 111192 - 111192

Опубликована: Ноя. 28, 2019

Язык: Английский

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Transcriptome Analysis of Long-lived Drosophila melanogaster E(z) Mutants Sheds Light on the Molecular Mechanisms of Longevity

Scientific Reports, Год журнала: 2019, Номер 9(1)

Опубликована: Июнь 24, 2019

Abstract The E ( z ) histone methyltransferase heterozygous mutation in Drosophila is known to increase lifespan and stress resistance. However, the longevity mechanisms of mutants have not been revealed. Using genome-wide transcriptome analysis, we demonstrated that extension, resistance hyperthermia, oxidative endoplasmic reticulum stress, fecundity enhancement are accompanied by changes expression level 239 genes (p < 0.05). Our results sex-specific effects on gene expression, which, however, did lead differences extension both sexes. We observed a an leads perturbations most which participates metabolism, such as Carbohydrate Lipid Drug Nucleotide metabolism. Age-dependent involved pathways related immune response, cell cycle, ribosome biogenesis were found.

Язык: Английский

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Ageing-associated changes in the expression of lncRNAs in human tissues reflect a transcriptional modulation in ageing pathways

Mechanisms of Ageing and Development, Год журнала: 2019, Номер 185, С. 111177 - 111177

Опубликована: Ноя. 9, 2019

Ageing-associated changes in the protein coding transcriptome have been extensively characterised, but less attention has paid to non-coding portion of human genome, especially long RNAs (lncRNAs). Only a minority known lncRNAs functionally characterised; however, handful these already linked ageing-associated processes. To gain more information on effects ageing lncRNAs, we identified from GTEx data that show expression patterns (age-lncRNAs) 29 tissues 20-79-year-old individuals. The age-lncRNAs were highly tissue-specific, genes co-expressed with and functional categories associated showed significant overlap across tissues. Functions age-lncRNAs, including immune system processes transcription, similar what previously reported for pattern. As tissue-specific shared functions tissues, they may reflect fine-tuning common present study can be utilised as resource when selecting prioritising further analyses.

Язык: Английский

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