Biology subjects

Fraifeld, V. E.

Publications and source records attributed to Fraifeld, V. E..

4 recordsLinked to original sources

bioRxiv2022

Drug prediction for reversing AD/PD transcriptional profiles using an aging of systems-centric approach

Age-related pathologies are so widely presented in old age that in most cases they are hardly distinguishable at the molecular level from the so-called normal aging. Both aging and age-related diseases are characterized by a wide range of transcriptional and epigenetic changes that underlie the physiological or pathological phenotype, with plenty of overlap in their signatures, but also with differences. In most pathological conditions it is rather the dysregulation of a complex network of genes than a problem with a single gene dysregulation that causes its emergence or progression, and aging differently gives a "predisposition" towards an age-related pathology or another, or in a favorable situation towards none. The important question is how similar are the transcriptional changes during "healthy" aging with those that occur in age-related diseases. In this study, we explore gene expression data to answer this question and aim to predict which drugs and compounds could have a reversing effect on their common drift.

bioinformatics↗

bioRxiv2019

Background radiation impacts human longevity and cancer mortality: Reconsidering the linear no-threshold paradigm

BACKGROUNDThe current linear-no-threshold paradigm assumes that any exposure to ionizing radiation carries some risk, thus every effort should be made to maintain the exposures as low as possible. Here, we examined whether background radiation impacts human longevity and cancer mortality.\n\nMETHODSOur data covered the entire US population of the 3139 US counties, encompassing over 320 million people. The data on background radiation levels, the average of 5-year age-adjusted cancer mortality rates, and life expectancy for both males and females in each county, was extracted using publicly available tools from official sources, and analyzed with JMP(R) software.\n\nRESULTSWe found for the first time that life expectancy, the most integrative index of population health, was approximately 2.5 years longer in people living in areas with a relatively high vs. low background radiation ([≥] 180 mrem/year and [≤] 100 mrem/year, respectively; p < 0.005; 95% confidence interval [CI]). This radiation-induced lifespan extension could to a great extent be associated with the decrease in cancer mortality rate observed for several common cancers (lung, pancreas and colon cancers for both genders, and brain and bladder cancers for males only; p < 0.05; 95% CI).\n\nCONCLUSIONSExposure to a high background radiation displays clear beneficial health effects in humans. These hormetic effects provide strong evidence for re-considering the linear no-threshold paradigm, at least within the natural range of low-dose radiation.

cancer biology↗

bioRxiv2019

A Multidimensional Systems Biology Analysis of Cellular Senescence in Ageing and Disease

Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of ageing and has been linked to ageing-related diseases like cancer. Senescent cells have been shown to accumulate in tissues of aged organisms which in turn can lead to chronic inflammation. Many genes have been associated with cell senescence, yet a comprehensive understanding of cell senescence pathways is still lacking. To this end, we created CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes associated with cellular senescence, and performed various integrative and functional analyses. We observed that genes promoting cell senescence tend to be overexpressed with age in human tissues and are also significantly overrepresented in anti-longevity and tumour-suppressor gene databases. By contrast, genes inhibiting cell senescence overlapped with pro-longevity genes and oncogenes. Furthermore, an evolutionary analysis revealed a strong conservation of senescence-associated genes in mammals, but not in invertebrates. Using the CellAge genes as seed nodes, we also built protein-protein interaction and co-expression networks. Clusters in the networks were enriched for cell cycle and immunological processes. Network topological parameters also revealed novel potential senescence-associated regulators. We then used siRNAs and observed that of 26 candidates tested, 19 induced markers of senescence. Overall, our work provides a new resource for researchers to study cell senescence and our systems biology analyses provide new insights and novel genes regarding cell senescence.

systems biology↗

bioRxiv2017

WIDE-SCALE COMPARATIVE ANALYSIS OF LONGEVITY GENES AND GENETIC INTERVENTIONS

Hundreds of genes have been identified as being involved in the control of lifespan in the four common model organisms (yeast, worm, fruit fly and mouse). A major challenge is to determine if longevity-associated genes (LAGs) are model-specific or may play a universal role as longevity regulators across diverse taxa. A wide-scale comparative analysis of the 1,805 known LAGs across 205 species revealed that (i) LAG orthologs are substantially over-represented, from bacteria to mammals, especially noted for essential LAGs; (ii) the effects on lifespan, when manipulating orthologous LAGs in different model organisms, were mostly concordant, despite of a high evolutionary distance between them; (iii) the most conserved LAGs were enriched in translational processes, energy metabolism, development, and DNA repair. The least conserved LAGs were enriched in autophagy (Fungi), G-proteins (Nematodes), and neuroactive ligand-receptor interactions (Chordata). The results also suggest that antagonistic pleiotropy is a conserved principle of aging.

systems biology↗