Background Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina. Methods Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing. Results We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota. Conclusions These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut–brain and gut–retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. Graphical abstract

Photoreceptors have high metabolic demands and age rapidly, undermining visual function. We base our understanding mainly on ageing mice where elevated inflammation, extracellular deposition, including that of amyloid beta, and rod and cone photoreceptor loss occur, but cones are not lost in ageing primate although their function declines, revealing that primate and mouse age differently. We examine ageing primate retinae and show elevated stress but low inflammation. However, aged primates have a >70% reduction in adenosine triphosphate (ATP) and a decrease in cytochrome c oxidase. There is a shift in cone mitochondrial positioning and glycolytic activity increases. Bruch’s membrane thickens but unlike in mice, amyloid beta is absent. Hence, reduced ATP may explain cone functional decline in ageing but their retained presence offers the possibility of functional restoration if they can be fuelled appropriately to restore cellular function. This is important because as humans we largely depend on cone function to see and are rarely fully dark adapted. Presence of limited aged inflammation and amyloid beta deposition question some of the therapeutic approaches taken to resolve problems of retinal ageing in humans and the possible lack of success in clinical trials in macular degeneration that have targeted inflammatory agents.

Photoreceptor cells have high energy demands and suffer significantly with age. In aged rodents both rods and cones are lost, but in primates there is no evidence for aged cone loss, although their function declines. Here we ask if aged primate cones suffer from reduced function because of declining metabolic ability. Tau is a microtubule associated protein critical for mitochondrial function in neurons. Its phosphorylation is a feature of neuronal degeneration undermining respiration and mitochondrial dynamics. We show that total tau is widely distributed in the primate outer retina with little age-related change, being present in both rods and cones and their processes. However, all cones specifically accumulate phosphorylated tau, which was not seen in rods. The presence of this protein will likely undermine cone cell function. However, tau phosphorylation inhibits apoptosis. These data may explain why aged primate cones have reduced function but appear to be resistant to cell death. Consequently, therapies designed to remove phosphorylated tau may carry the risk of inducing cone photoreceptor cell death and further undermine ageing visual function.

This research was aimed at estimating the effect of oral supplementation of Tamoxifen on productive efficiency, carcass characteristics, hormonal profile and gonadal structure of two broiler breeds. One hundred and eighty chicks of each breed of Avian48 and Arbor Acres were divided into three groups: control group; TAM10 group, supplied with 10 mg Tamoxifen/kg of body weight at 3, 5, 7 and 9 days of life; and TAM20 group, supplied at the same intervals with 20 mg Tamoxifen/kg of body weight. Both levels of Tamoxifen improved productive performance at early ages, but Arbor Acres produced better results with TAM20 levels than TAM10, while Avian48 breeds reacted adversely. On the contrary, Tamoxifen supplementation significantly decreased feed intake and feed conversion (after the first two weeks of life) compared to control with a higher level of decrease reported for TAM20 treatments than TAM10 and for Arbor Acres compared to Avian48 breed. Carcass traits were not affected significantly with Tamoxifen supplementation compared to control although Arbor Acres responded better to TAM20 and Avian48 for TAM10. With regard to the effect of Tamoxifen (TAM) on sex hormones, it could be concluded that TAM10 treatments showed a stimulating effect on the level of such hormones as compared with the TAM20 group with the most favourable results being clearly detectable in 42-day-old birds although both concentrations of Tamoxifen did not differ significantly from control. However, treatment of broiler chickens with Tamoxifen in different doses caused a gradual decrease in follicle production rate and eventually led to an increase of the atretic follicles in different stages of atresia. Finally, we can conclude that Tamoxifen supplementation can improve performance and carcass efficiency of broilers without changing the hormonal profile, however much research is required to estimate the best concentration required for each breed.

Bats are the only mammals that can fly in the dark without eye usage. This study was conducted to describe the structural and functional adaptations of the retina of two bats very common in the Egyptian fauna having a different lifestyle: the Egyptian fruit bat (Rousettus aegyptiacus) and insectivorous bat (Pipistrellus kuhlii). Seven eyes were collected from adult individuals of each species. Examination of the retina using a light microscope and a transmission electron microscope was carried out. The retina of P. kuhlii was thicker than that of R. aegyptiacus, which had many projections extended from the choroid layer into retina forming papillae. Despite rods being dominant in retinae of both species, cone photoreceptors were encountered in both retinae. The outer plexiform layer of R. aegyptiacus was arranged into islets between the outer nuclear layer produced differences in its thickness. However, the retina of P. kuhlii showed a normal arrangement of retinal structure. The retinal pigment epithelium of both bat species consists of a single layer of the cuboidal cells with a round to oval vesicular nuclei, which showed a lack of pigmentation in R. aegyptiacus and poor pigmentation in the P. kuhlii. In conclusion, our investigation detected many structural and ultrastructural differences between the two bat species. The presence of many projections protruded from the choroid layer of R. aegyptiacus retina is considered the most characteristic difference between the retinae of R. aegyptiacus and

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Mitochondrial function declines with age and in some diseases, but we have been unable to analyze this in vivo. Here, we optically examine retinal mitochondrial function as well as choroidal oxygenation and hemodynamics in aging C57 and complement factor H (CFH−/−) mice, proposed models of macular degeneration which suffer early retinal mitochondrial decline. In young C57s mitochondrial populations respire in coupled oscillatory behavior in cycles of ~ 8 min, which is phase linked to choroidal oscillatory hemodynamics. In aging C57s, the oscillations are less regular being ~ 14 min and more dissociated from choroidal hemodynamics. The mitochondrial oscillatory cycles are extended in CFH−/− mice being ~ 16 min and are further dissociated from choroidal hemodynamics. Mitochondrial decline occurs before age-related changes to choroidal vasculature, hence, is the likely origin of oscillatory disruption in hemodynamics. This technology offers a non-invasive technique to detect early retinal disease and its relationship to blood oxygenation in vivo and in real time.

Lectins are glycoproteins of a non-immune origin often used as histochemical reagents to study the distribution of glycoconjugates in different types of tissues. In this study, we performed a comparative cellular localization of sugar residues in bull and donkey testes using immunofluorescent lectin histochemistry. We inspected the cellular localization of the glycoconjugates within the testes using 11 biotin-labeled lectins (LCA, ConA, PNA, WGA, DBA, SBA, ECA, BPL, PTL-II, UEA-1, and PHA-E4) classified under six groups. Although the basic testicular structure in both species was similar, the cellular components showed different lectin localization patterns. The statistical analysis revealed no significant association between the intensity of labeling and different variables, including group and type of lectin and type of cell examined, at p < 0.05. However, a stronger response tended to occur in the donkey than in the bull testes (odds ratio: 1.3). These findings may be associated with the different cellular compositions of the glycoproteins and modification changes during spermatogenesis. Moreover, glycoconjugate profiling through lectin histochemistry can characterize some cell-type selective markers that will be helpful in studying bull and donkey spermatogenesis.