Biology subjects

Bar, D. Z.

Publications and source records attributed to Bar, D. Z..

4 recordsLinked to original sources

bioRxiv2023

Epigenetic information loss is a common feature of multiple diseases and aging

Aging is a major risk factor for a plethora of diseases. The information theory of aging posits that epigenetic information loss is a principal driver of the aging process. Despite this, the connection between epigenetic information loss and disease has not been thoroughly investigated. Here, we analyzed tissue-unique methylation patterns in healthy and diseased organs, revealing that for several diseases these patterns degrade, regressing to a mean form. We interpret this as epigenetic information loss, where tissue-unique patterns erode. Information loss is not limited to diseases. Age-related erosion of unique methylation patterns was observed in some tissues and cells, while other tissues and cells diverged away from the mean. Our findings demonstrate that analyzing methylation patterns in tissue-unique sites can effectively distinguish between patients and healthy controls across a range of diseases, and underscore the role of epigenetic information loss as a common feature in various pathological conditions. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/539727v3_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@12049e0org.highwire.dtl.DTLVardef@d214c7org.highwire.dtl.DTLVardef@52425forg.highwire.dtl.DTLVardef@839011_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Tissue unique methylation pattern regress toward the mean upon disease. A single methylation site, showing low methylation in the liver and high in every other tissue, becomes more methylated in diseased livers. C_FIG

molecular biology↗

bioRxiv2022

Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression

Chronological and biological age correlate with DNA methylation levels at specific sites in the genome. Linear combinations of multiple methylation sites, termed epigenetic clocks, can inform us of the chronological age and predict multiple health-related outcomes. However, why some sites correlate with lifespan, healthspan, or specific medical conditions remains poorly understood. Kidney fibrosis is the common pathway for Chronic Kidney Disease, which affects 10% of Europe and USA population. Here we identify epigenetic clocks and methylation sites that correlate with kidney function. Moreover, we identify methylation sites that have a unique methylation signature in the kidney. Methylation levels in the majority of these sites correlates with kidney state and function. When kidney function deteriorates, all of these sites regress towards the common methylation pattern observed in other tissues. Interestingly, while the majority of sites are less methylated in the kidney and become more methylated with loss of function, a fraction of the sites are highly methylated in the kidney and become less methylated when kidney function declines. These methylation sites are enriched for specific transcription-factor binding sites. In a large subset of sites, changes in methylation pattern are accompanied by changes in gene expression in kidneys of chronic kidney disease patients. These results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines. However, this information loss is not random, but guided towards a baseline that is dependent on the genomic loci.

bioinformatics↗

bioRxiv2022

The hidden secrets of the dental calculus: Calibration of a mass spectrometry protocol for dental calculus protein analysis

Dental calculus is a solid deposit that forms and accumulates on the tooth surface, entrapping oral microorganisms, biomolecules, and other micro-debris found in the oral cavity. Mass spectrometry analysis of its protein content opens a vista into the subjects diet, oral flora, and even some aspects of health, thus providing new insight and expanding our knowledge of archaic cultures. Multiple experimental protocols have been proposed for the optimal extraction of proteins from dental calculus. Herein, we compared various experimental conditions in order to calibrate and validate a protocol for protein extraction. Our results show that a high concentration of acetic acid followed by mechanical crushing and sonication provided the highest protein yield, while acetone precipitation enabled the identification of more distinct proteins. We validated this protocol using archeological samples, identifying human and microbial proteins in specimens from the 8th and 17th centuries (approximately 250-1300 years ago). These findings demonstrate that the developed protocol is useful for studying excavated archaeological samples and that it might be utilized to explore the biohistory, dietary habits, and microbiome of archaic populations.

molecular biology↗

bioRxiv2020

Lamin regulates the dietary restriction response via the mTOR pathway in Caenorhabditis elegans

Animals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation of lmn-1, the single Caenorhabditis elegans lamin gene, increased animal size and fat content, specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream to RAPTOR and S6K, key component and target of mTOR complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation of lmn-1 restores RAGC-1 to the nucleus, a necessary step for the activation of the mTOR pathway. These findings further link lamin to metabolic regulation.

cell biology↗