Defects in MAP1S‐mediated autophagy cause reduction in mouse lifespans especially when fibronectin is overexpressed

Autophagy is a cellular process that executes the turnover of dysfunctional organelles and misfolded or abnormally aggregated proteins. Microtubule‐associated protein MAP1S interacts with autophagy marker LC3 and positively regulates autophagy flux. LC3 binds with fibronectinmRNA and facilitates its translation. The synthesized fibronectin protein is exported to cell surface to initiate the assembly of fibronectin extracellular matrix. Fibronectin is degraded in lysosomes after it is engulfed into cytosol via endocytosis. Here, we show that defects in MAP1S‐mediated autophagy trigger oxidative stress, sinusoidal dilation, and lifespan reduction. Overexpression of LC3 in wild‐type mice increases the levels of fibronectin and γ‐H₂AX, a marker of DNA double‐strand breakage. LC3‐induced fibronectin is efficiently degraded in lysosomes to maintain a balance of fibronectin levels in wild‐type mice so that the mice live a normal term of lifespan. In the LC3 transgenic mice with MAP1S deleted, LC3 enhances the synthesis of fibronectin but the MAP1S depletion causes an impairment of the lysosomal degradation of fibronectin. The accumulation of fibronectin protein promotes liver fibrosis, induces an accumulation of cell population at the G0/G1 stage, and further intensifies oxidative stress and sinusoidal dilatation. The LC3‐induced overexpression of fibronectin imposes stresses on MAP1S‐deficient mice and dramatically reduces their lifespans. Therefore, MAP1S‐mediated autophagy plays an important role in maintaining mouse lifespan especially in the presence of extra amount of fibronectin.     

Aneuploidy shortens replicative lifespan in Saccharomyces cerevisiae

Aneuploidy and aging are correlated; however, a causal link between these two phenomena has remained elusive. Here, we show that yeast disomic for a single native yeast chromosome generally have a decreased replicative lifespan. In addition, the extent of this lifespan deficit correlates with the size of the extra chromosome. We identified a mutation in BUL1 that rescues both the lifespan deficit and a protein trafficking defect in yeast disomic for chromosome 5. Bul1 is an E4 ubiquitin ligase adaptor involved in a protein quality control pathway that targets membrane proteins for endocytosis and destruction in the lysosomal vacuole, thereby maintaining protein homeostasis. Concurrent suppression of the aging and trafficking phenotypes suggests that disrupted membrane protein homeostasis in aneuploid yeast may contribute to their accelerated aging. The data reported here demonstrate that aneuploidy can impair protein homeostasis, shorten lifespan, and may contribute to age‐associated phenotypes.     

Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic

In the coming decades, a massive shift in the aging segment of the population will have major social and economic consequences around the world. One way to offset this increase is to expedite the development of geroprotectors, substances that slow aging, repair age‐associated damage and extend healthy lifespan, or healthspan. While over 200 geroprotectors are now reported in model organisms and some are in human use for specific disease indications, the path toward determining whether they affect aging in humans remains obscure. Translation to the clinic is hampered by multiple issues including absence of a common set of criteria to define, select, and classify these substances, given the complexity of the aging process and their enormous diversity in mechanism of action. Translational research efforts would benefit from the formation of a scientific consensus on the following: the definition of ‘geroprotector’, the selection criteria for geroprotectors, a comprehensive classification system, and an analytical model. Here, we review current approaches to selection and put forth our own suggested selection criteria. Standardizing selection of geroprotectors will streamline discovery and analysis of new candidates, saving time and cost involved in translation to clinic.     

Restoring the youth of aged red blood cells and extending their lifespan in circulation by remodelling membrane sialic acid

Membrane sialic acid (SA) plays an important role in the survival of red blood cells (RBCs), the age‐related reduction in SA content negatively impacts both the structure and function of these cells. We have therefore suggested that remodelling the SA in the membrane of aged cells would help recover cellular functions characteristic of young RBCs. We developed an effective method for the re‐sialylation of aged RBCs by which the cells were incubated with SA in the presence of cytidine triphosphate (CTP) and α‐2,3‐sialytransferase. We found that RBCs could be re‐sialylated if they had available SA‐binding groups and after the re‐sialylation, aged RBCs could restore their membrane SA to the level in young RBCs. Once the membrane SA was restored, the aged RBCs showed recovery of their biophysical and biochemical properties to similar levels as in young RBCs. Their life span in circulation was also extended to twofold. Our findings indicate that remodelling membrane SA not only helps restore the youth of aged RBCs, but also helps recover injured RBCs.     

Rapid turnover of traps in Utricularia vulgaris L.

Summary Utricularia vulgaris growing at Wicken Fen, England, showed rapid turnover of the trapping apparatus. New groups of leaves, each bearing many traps, were produced at a rate of 1.4–2.8 groups per day from April to September, 1987. Old leaves decayed at a comparable rate, so that individual leaves survived for less than 50 days. In July, trapping efficiency of individual bladders was greatest between 1 and 6 days of age and then declined rapidly. Very few traps more than 19 days old could capture prey and most were lost from the leaves within 32 days. The lifespan of traps was closely related to their size and position on the leaves. Because of the rapidity of changes in trap condition with age, trap age is a vital consideration in any studies of the functional ecology of U. vulgaris     

Specificity of the α-tocopherol (Vitamin E) effect on lifespan and fecundity of bdelloid rotifers

Experiments were undertaken to determine molecular specificity of Vitamin E-effects on lifespan and fecundity in four bdelloid rotifers (Habrotrocha sp., Philodina sp., Pleuretra sp., and Rotaria sp.). Results indicate that lifespan and fecundity could be significantly increased by addition of any one of three tocopherol compounds (d--, -, and -tocopherol) to the rotifer medium. Life table functions were increased the most by the d--tocopherol form. Improvement of these life table functions was not achieved by substitution of tocopherol analogs or other antioxidants in the rotifer medium.     

Sex ratio distortion and reduced lifespan of Glossina pallidipes infected with the virus causing salivary gland hyperplasia

A virus infection, associated with enlargement of the salivary glands (ESG) and gonadal pathology in Glossina pallidipes Austen (Diptera: Glossinidae), was studied in field-caught and laboratory-reared flies. The lifespan of both sexes of infected (ESG-) flies was significantly shorter than that of flies with normal salivary glands (NSG). NSG-females, mated to infected males only or to both infected and normal males, produced predominantly male progeny. In general, NSG-parents produced only NSG-progeny, and ESG-females only ESG-progeny. ESG-males were usually sterile, but a few NSG-females inseminated by ESG-males produced NSG-progeny. One NSG-female, mated first to an ESG-male and then to an NSG-male, produced 3 ESG-sons. As will be discussed, this virus may have important effects (reduced insemination rates, fecundity and lifespan, and sex ratio distortion) on laboratory colonies of G. pallidipes as well as on the regulation of its natural populations.

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Résumé C'est à partir de mouches capturées et élevées au laboratoire à Kibwezi au Kenya, qu'a été étudiée l'infection virale, accompagnée d'hyperplasie des glandes salivaires (ESG) et la pathologie des gonades de G. pallidipes Aust. La durée de vie des mouches contaminées (ESG)_des 2 sexes était significativement plus brève que celle des mouches aux glandes salivaires normales (NSG). Des femelles NSG accouplées uniquement à des mâles contaminés ou à des mâles sains et contaminés, ont donné une descendance majoritairement mâle.En général, des parents NSG ont donné uniquement des enfants NSG, et des femelles ESG des enfants ESG. Les mâles ESG étaient généralement stériles, mais quelques femelles NSG inséminées par des mâles ESG ont donné des enfants NSG. Une femelle NSG accouplée en premier avec un mâle ESG et ensuite à un mâle NSG, a donné 3 fils ESG. Bien que les transmissions orales et sexuelles puissent être naturellement des modes de contamination, la transmission verticale de la mère à la descendance semble être le mécanisme le plus significatif du maintien de ce virus. L'apparition d'enfants ESG de parents NSG est dans quelques cas vraisemblablement due à la présence du virus chez quelques mouches NSG sans qu'il y ait apparemment infection, sans symptômes visibles. Le virus ESG peut avoir des effets importants (diminution des taux d'insémination, de la fécondité, de la durée de vie, et modification de la fréquence des sexes) dans les souches de laboratoire et aussi sur la régulation des populations naturelles de ce vecteur des trypanosomiases africaines.

     

Comparative life‐history traits in a fig wasp community: implications for community structure

1. Whether life‐history traits can determine community composition and structure is an important question that has been well explored theoretically, but has received scant empirical attention. Life‐history traits of a seven‐member community of galler and parasitoid fig wasp species (Chalcidoidea), developing within the inflorescences (syconia) of Ficus racemosa (Moraceae) in India, were determined and used to examine community structure and ecology. 2. Gallers were pro‐ovigenic (all eggs are mature upon adult emergence) whereas parasitoids were synovigenic (eggs mature progressively during adult lifespan). Initial egg load was correlated with body size for some species, and there was a trade‐off between egg number and egg size across all species. Although all species completed their development and left the syconium concurrently, they differed in their adult and pre‐adult lifespans. Providing sucrose solutions increased parasitoid lifespan but had no effect on the longevity of some galler species. While feeding regimes and body size affected longevity in most species, an interaction effect between these variables was detected for only one species. 3. Life‐history traits of wasp species exhibited a continuum in relation to their arrival sequence at syconia for oviposition during syconium development, and therefore reflected their ecology. The largest number of eggs, smallest egg sizes, and shortest longevities were characteristic of the earliest‐arriving galling wasps at the smallest, immature syconia; the converse characterised the later‐arriving parasitoids at the larger, already parasitised syconia. Thus life history is an important correlate of community resource partitioning and can be used to understand community structure. 4. This is the first comprehensive study of life‐history traits in a fig wasp community. The comparative approach revealed constraints and flexibility in trait evolution.     

Do traits of plant species predict the efficacy of species distribution models for finding new occurrences?

Species distribution models (SDMs) are used to test ecological theory and to direct targeted surveys for species of conservation concern. Several studies have tested for an influence of species traits on the predictive accuracy of SDMs. However, most used the same set of environmental predictors for all species and/or did not use truly independent data to test SDM accuracy. We built eight SDMs for each of 24 plant species of conservation concern, varying the environmental predictors included in each SDM version. We then measured the accuracy of each SDM using independent presence and absence data to calculate area under the receiver operating characteristic curve (AUC) and true positive rate (TPR). We used generalized linear mixed models to test for a relationship between species traits and SDM accuracy, while accounting for variation in SDM performance that might be introduced by different predictor sets. All traits affected one or both SDM accuracy measures. Species with lighter seeds, animal‐dispersed seeds, and a higher density of occurrences had higher AUC and TPR than other species, all else being equal. Long‐lived woody species had higher AUC than herbaceous species, but lower TPR. These results support the hypothesis that the strength of species–environment correlations is affected by characteristics of species or their geographic distributions. However, because each species has multiple traits, and because AUC and TPR can be affected differently, there is no straightforward way to determine a priori which species will yield useful SDMs based on their traits. Most species yielded at least one useful SDM. Therefore, it is worthwhile to build and test SDMs for the purpose of finding new populations of plant species of conservation concern, regardless of these species’ traits.