Biology subjects

Ibrahim, S. M.

Publications and source records attributed to Ibrahim, S. M..

4 recordsLinked to original sources

bioRxiv2025

Proteo-transcriptomic reprogramming and resource reallocation define the aging mammalian brain

Brain aging is a major risk for neurodegeneration, yet the underlying molecular mechanisms remain poorly understood. Here we performed an integrative proteo-transcriptomic analysis of the aging mouse brain, uncovering molecular signatures of aging through the assessment of protein aggregation, mRNA relocalization, and comparative proteomics across eight models of premature aging and neurodegeneration. We identified dynamic changes in physiological aging highlighting differences in synaptic maintenance and energy-allocation. These were linked to changes associated with fundamental protein biochemical properties such as size and net charge. Network analysis highlighted a decrease in mitochondrial complex I proteins not compensated at the mRNA level. Aggregation of 60S ribosome subunits indicated deteriorating translation efficiency and was accompanied by mitochondrial and proteasomal imbalance. The analysis of the nine models revealed key similarities and differences between physiological aging and pathology. Overall, our study provides an extensive resource on molecular aging, and offers insights into mechanisms predisposing to neurodegeneration, easily accessible at our Brain Aging and Molecular Atlas Project (BrainAging-MAP) website.

neuroscience↗

bioRxiv2022

A comprehensive analysis of the gut and skin microbiota in canine atopic dermatitis in Shiba Inu dogs

BackgroundLike its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies. Therefore, we conducted a comprehensive analysis of both gut and skin microbiota in cAD in one specific cAD-predisposed breed, Shiba Inu. Additionally, we evaluated the impact of commonly used medical management on cAD (Janus kinase; JAK inhibitor, oclacitinib) on the gut and skin microbiota. Furthermore, we genotyped the Shiba Inu dogs according to the mitochondrial DNA haplogroup and assessed its association with the composition of the gut microbiota. ResultsStaphylococcus was the most predominant bacterial genus observed in the skin; Escherichia/Shigella and Clostridium sensu stricto were highly abundant in the gut of cAD-affected dogs. In the gut microbiota, Fusobacteria and Megamonas were highly abundant in healthy dogs but significantly reduced in cAD-affected dogs. The abundance of these bacterial taxa was positively correlated with the effect of the treatment and state of the disease. Oclacitinib treatment on cAD-affected dogs shifted the composition of microbiota towards that in healthy dogs, and the latter brought it much closer to healthy microbiota, particularly in the gut. Additionally, even within the same dog breed, the mtDNA haplogroup varied, and there was an association between the mtDNA haplogroup and gut microbial composition. ConclusionsDysbiosis of both the skin and the gut was observed in cAD in Shiba Inu dogs. Our findings provide a basis for the potential treatment of cAD by manipulating the gut microbiota as well as the skin microbiota.

microbiology↗

bioRxiv2018

Maternally inherited differences within mitochondrial Complex I control murine healthspan.

Mitochondrial complex I, the largest enzyme complex of the mitochondrial oxidative phosphorylation machinery, has been proposed to contribute to a variety of age-related pathological alterations as well as longevity. The enzyme complex-consisting proteins are encoded by both nuclear (nDNA) and mitochondrial DNA (mtDNA). While some association studies of mtDNA-encoded complex I genes and lifespan in humans have been reported, experimental evidence and the functional consequence of such variants is limited to studies using invertebrate models. Here, we present experimental evidence that a homoplasmic mutation in the mitochondrially encoded complex I gene mt-Nd2 modulates lifespan by altering cellular tryptophan levels and, consequently, ageing-related pathways in mice. A conplastic mouse strain carrying a mutation at m.4738C>A in mt-Nd2 lived significantly shorter than the controls did. The same mutation led to a higher susceptibility to glucose intolerance induced by high-fat diet feeding. These phenotypes were not observed in mice carrying a mutation in another mtDNA-encoded complex I gene, mt-Nd5, suggesting the functional relevance of particular mutations in complex I to ageing and age-related diseases.

genetics↗

bioRxiv2017

Low-level mitochondrial heteroplasmy modulates DNA replication, glucose metabolism and lifespan in mice

Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e. the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum of diseases but also physiological processes, including endurance exercise performance in athletes. However, the phenotypic consequences of limited levels of naturally-arising heteroplasmy have not been experimentally studied to date. We hence generated a conplastic mouse strain carrying the mitochondrial genome of a AKR/J mouse strain (B6-mtAKR) together with a C57BL/6J nuclear genomic background, leading to >20% heteroplasmy in the origin of light-strand DNA replication (OriL). These conplastic mice demonstrate a shorter lifespan as well as dysregulation of multiple metabolic pathways, culminating in impaired glucose metabolism, compared to wild-type C57BL/6J mice carrying lower levels of heteroplasmy. Our results indicate that physiologically relevant differences in mtDNA heteroplasmy levels at a single, functionally important site impair metabolic health and lifespan in mice.\n\nHighlightsO_LIWe identify heteroplasmy of the adenine-repeat variation (9 to 13A) in nt5172 in the origin of light-strand DNA replication (OriL) in inbred mice.\nC_LIO_LIB6-mtAKR mice carry >20% 12A heteroplasmy in the OriL, while B6 mice carry only [~] 10% heteroplasmy.\nC_LIO_LIThe level of 12A heteroplasmy correlates to mtDNA copy number, glucose metabolism, and lifespan in mice.\nC_LIO_LIGiven the established role of mtDNA heteroplasmy in regards to endurance exercise performance in athletes, these findings may impact our understanding of metabolism and aging in humans.\nC_LI

genetics↗