Biology subjects

Bektas, A.

Publications and source records attributed to Bektas, A..

3 recordsLinked to original sources

bioRxiv2025

The blood proteome predicts the impact of circulating factors on age-related mitochondrial health

Circulating non-cellular factors, such as plasma proteins, contribute to various features of aging. To determine the impacts of endogenous circulating factors on human age-related bioenergetic decline, we treated primary human fibroblasts with serum samples representing the adult life-course. Our results demonstrate that the maximal mitochondrial bioenergetic capacity of fibroblasts treated with serum is negatively correlated with the chronological and epigenetic age of the serum donor. Using targeted proteomics, we identified plasma proteins associated with the bioenergetic effects of serum. We then utilized elastic net, a linear regression modeling technique, to derive a novel proteomic signature of age-related mitochondrial differences. MitoAge is a 25-protein signature of age-related mitochondrial health that predicts the systemic bioenergetic effects of circulating factors and is related to differences in physical function across human aging. Signatures that report on cellular hallmarks of aging, such as mitochondrial function, represent a new generation of mechanistically-informed biomarkers of biological aging. GRAPHICAL ABSTRACTIn this study, we describe the development of a novel proteomic signature, MitoAge. This signature was developed by utilizing human primary fibroblasts treated with serum samples representing the adult human life-course and analyzing how resulting respirometry correlated with chronological age, epigenetic age, and abundance of serum proteins. Utilizing machine learning techniques, we derived a 25-protein signature which can predict bioenergetics and physical features related to aging. Application and utility of this signature may be used to identify novel drivers of health and longevity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/687483v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@905c12org.highwire.dtl.DTLVardef@18ca82forg.highwire.dtl.DTLVardef@175d397org.highwire.dtl.DTLVardef@966faa_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Epigenetic signature of human immune aging: the GESTALT study.

Age-associated DNA methylation in blood cells convey information on health status. However, the mechanisms that drive these changes in circulating cells and their relationships to gene regulation are unknown. We identified age-associated DNA methylation sites in six purified blood borne immune cell types (naive B, naive CD4+and CD8+ T cells, granulocytes, monocytes and NK cells) collected from healthy individuals interspersed over a wide age range. Of the thousand of age-associated sites, only 350 sites were differentially methylated in the same direction in all cell types and validated in an independent longitudinal cohort. Genes close to age-associated hypomethylated sites were enriched for collagen biosynthesis and complement cascade pathways, while genes close to hypermethylated sites mapped to neuronal pathways. In-silico analyses showed that in most cell types, the age-associated hypo- and hypermethylated sites were enriched for ARNT (HIF1{beta}) and REST transcription factor motifs respectively, which are both master regulators of hypoxia response. To conclude, despite spatial heterogeneity, there is a commonality in the putative regulatory role with respect to transcription factor motifs and histone modifications at and around these sites. These features suggest that DNA methylation changes in healthy aging may be adaptive responses to fluctuations of oxygen availability.

molecular biology↗

bioRxiv2021

HiIDDD: A high-throughput imaging pipeline for the quantitative detection of DNA damage in primary human immune cells

DNA damage is a prominent biomarker for numerous diseases, including cancer and aging. Detection of DNA damage routinely relies on traditional microscopy or cytometric methods. However, these techniques are typically of limited throughput and are not ideally suited for large-scale longitudinal and population studies that require analysis of large sample sets. We have developed HiIDDD (High-throughput Immune cell DNA Damage Detection), a robust, semiquantitative and single-cell assay that measures DNA damage by high-throughput imaging using the two major DNA damage markers 53BP1 and {gamma}-H2AX. We demonstrate sensitive detection of DNA damage in a wide set of freshly isolated and cryopreserved primary human immune cells, including CD4+ and CD8+ T cells, B cells and monocytes with low inter-assay variability. As proof of principle, we demonstrate parallel batch processing of several immune cell types from multiple donors. We find common patterns of DNA damage in multiple immune cell types of donors of varying ages, suggesting that immune cell properties are specific to individuals. These results establish a novel high-throughput assay for the evaluation of DNA damage in large-scale studies.

cell biology↗