The turquoise killifish: a genetically tractable model for the study of aging.

Lifespan is a remarkably diverse trait in nature, ranging from just hours in adult mayflies to hundreds of years in the Greenland shark and quahog clam. Great disparities in lifespan are often observed even among somewhat closely related species; for example, in the laboratory, wild-derived strains of the common house mouse have a maximum observed lifespan of approximately 6 years, while a similarly sized rodent, the naked mole rat, can live for over 30 years. Comparative biology of aging across the tree of life provides a tremendous opportunity for understanding the molecular and genetic basis underlying lifespan and aging. However, a lack of molecular and laboratory tools has limited the ability of researchers to take full advantage of the incredible diversity of aging phenotypes in nature. Recent developments in genomic technology have made it increasingly possible to study non-canonical model organisms for aging. One promising new genetic model organism amenable to a range of experimental interventions is the turquoise killifish (Nothobranchius furzeri). This fish species has a naturally short lifespan and undergoes a wide range of aging-related transformations. These fish have a fully sequenced genome and transcriptome, and killifish embryos are accessible to transgenesis and genome editing. Furthermore, different killifish species and populations show striking differences in lifespan, providing the opportunity for comparative analysis of aging. This Review introduces the natural life history of the turquoise killifish, its emerging applicability as an aging model system, the genetic tools that have been developed to study aging for this species and a summary of recent studies facilitated by these new tools.

Gender identity rather than sexual orientation impacts on facial preferences.

INTRODUCTION: Differences in facial preferences between heterosexual men and women are well documented. It is still a matter of debate, however, how variations in sexual identity/sexual orientation may modify the facial preferences. AIM: This study aims to investigate the facial preferences of male-to-female (MtF) individuals with gender dysphoria (GD) and the influence of short-term/long-term relationships on facial preference, in comparison with healthy subjects. METHODS: Eighteen untreated MtF subjects, 30 heterosexual males, 64 heterosexual females, and 42 homosexual males from university students/staff, at gay events, and in Gender Clinics were shown a composite male or female face. The sexual dimorphism of these pictures was stressed or reduced in a continuous fashion through an open-source morphing program with a sequence of 21 pictures of the same face warped from a feminized to a masculinized shape. MAIN OUTCOME MEASURES: An open-source morphing program (gtkmorph) based on the X-Morph algorithm. RESULTS: MtF GD subjects and heterosexual females showed the same pattern of preferences: a clear preference for less dimorphic (more feminized) faces for both short- and long-term relationships. Conversely, both heterosexual and homosexual men selected significantly much more dimorphic faces, showing a preference for hyperfeminized and hypermasculinized faces, respectively. CONCLUSIONS: These data show that the facial preferences of MtF GD individuals mirror those of the sex congruent with their gender identity. Conversely, heterosexual males trace the facial preferences of homosexual men, indicating that changes in sexual orientation do not substantially affect preference for the most attractive faces.

Turquoise killifish: A natural model of age-dependent brain degeneration.

Turquoise killifish (Nothobranchius furzeri) are naturally short-lived vertebrates that display a wide range of spontaneous age-related changes, including onset of cancer, reduced mobility, and cognitive decline. Here, we focus on describing the phenotypic spectrum of the aging killifish brain. As turquoise killifish age, their dopaminergic and noradrenergic neurons undergo a significant decline in number. Furthermore, brain aging in turquoise killifish is associated with several glial-specific changes, such as an increase in the astrocyte-covered surface area and an increase in the numbers of microglial cells, i.e. the brain-specific macrophage population. Killifish brains undergo age-dependent reduced proteasome activity and increased protein aggregation, including the aggregation of the Parkinson's disease marker α-synuclein. Parallel to brain degeneration, turquoise killifish develop spontaneous age-related gut dysbiosis, which has been proposed to affect human neurodegenerative disease. Finally, aged turquoise killifish display declined learning capacity. We argue that, taken together, the molecular, cellular and functional changes that spontaneously take place during aging in killifish brains are consistent with a robust degenerative process that shares remarkable similarities with human neurodegenerative diseases. Hence, we propose that turquoise killifish represent a powerful model of spontaneous brain degeneration which can be effectively used to explore the causal mechanisms underlying neurodegenerative diseases.

Transcriptomes of aging brain, heart, muscle, and spleen from female and male African turquoise killifish.

The African turquoise killifish is an emerging vertebrate model organism with great potential for aging research due to its naturally short lifespan. Thus far, turquoise killifish aging 'omic' studies have examined a single organ, single sex and/or evaluated samples from non-reference strains. Here, we describe a resource dataset of ribosomal RNA-depleted RNA-seq libraries generated from the brain, heart, muscle, and spleen from both sexes, as well as young and old animals, in the reference GRZ turquoise killifish strain. We provide basic quality control steps and demonstrate the utility of our dataset by performing differential gene expression and gene ontology analyses by age and sex. Importantly, we show that age has a greater impact than sex on transcriptional landscapes across probed tissues. Finally, we confirm transcription of transposable elements (TEs), which are highly abundant and increase in expression with age in brain tissue. This dataset will be a useful resource for exploring gene and TE expression as a function of both age and sex in a powerful naturally short-lived vertebrate model.

Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate.

Resveratrol, a natural phytoalexin found in grapes and red wine, increases longevity in the short-lived invertebrates Caenorhabditis elegans and Drosophila and exerts a variety of biological effects in vertebrates, including protection from ischemia and neurotoxicity. Its effects on vertebrate lifespan were not yet known. The relatively long lifespan of mice, which live at least 2.5 years, is a hurdle for life-long pharmacological trials. Here, the authors used the short-lived seasonal fish Nothobranchius furzeri with a maximum recorded lifespan of 13 weeks in captivity. Short lifespan in this species is not the result of spontaneous or targeted genetic mutations, but a natural trait correlated with the necessity to breed in an ephemeral habitat and tied with accelerated development and expression of ageing biomarkers at a cellular level. Resveratrol was added to the food starting in early adulthood and caused a dose-dependent increase of median and maximum lifespan. In addition, resveratrol delays the age-dependent decay of locomotor activity and cognitive performances and reduces the expression of neurofibrillary degeneration in the brain. These results demonstrate that food supplementation with resveratrol prolongs lifespan and retards the expression of age-dependent traits in a short-lived vertebrate.

Temperature affects longevity and age-related locomotor and cognitive decay in the short-lived fish Nothobranchius furzeri.

Temperature variations are known to modulate aging and life-history traits in poikilotherms as different as worms, flies and fish. In invertebrates, temperature affects lifespan by modulating the slope of age-dependent acceleration in death rate, which is thought to reflect the rate of age-related damage accumulation. Here, we studied the effects of temperature on aging kinetics, aging-related behavioural deficits, and age-associated histological markers of senescence in the short-lived fish Nothobranchius furzeri. This species shows a maximum captive lifespan of only 3 months, which is tied with acceleration in growth and expression of aging biomarkers. These biological peculiarities make it a very convenient animal model for testing the effects of experimental manipulations on life-history traits in vertebrates. Here, we show that (i) lowering temperature from 25 degrees C to 22 degrees C increases both median and maximum lifespan; (ii) life extension is due to reduction in the slope of the age-dependent acceleration in death rate; (iii) lowering temperature from 25 degrees C to 22 degrees C retards the onset of age-related locomotor and learning deficits; and (iv) lowering temperature from 25 degrees C to 22 degrees C reduces the accumulation of the age-related marker lipofuscin. We conclude that lowering water temperature is a simple experimental manipulation which retards the rate of age-related damage accumulation in this short-lived species.

Neurophysiological correlates for the perception of facial sexual dimorphism.

Neural correlates for the processing of face identity, expression, gaze direction and attractiveness are well described, but neurophysiological correlates for the perception of face gender are less understood. Here, we used morphing techniques to produce synthetic faces with graded perceivable gender and independent component analysis (ICA) of multifocal EEG to unravel neural signals correlated to processing and perception of face gender. We investigate possible neural correlates of face perception using scalp event-related potentials (ERPs) and dipole source analysis in a group of health observers. We isolated one signal source localised to the right parieto-temporal region with a latency of about 170 ms, whose latency correlates with perceived facial masculinity. In conclusion, our data prove that the right parieto-temporal regions play a fundamental role in face gender masculinity processing and perception in humans.

From the bush to the bench: the annual Nothobranchius fishes as a new model system in biology.

African annual fishes from the genus Nothobranchius are small teleosts that inhabit temporary water bodies subject to annual desiccation due to the alternation of the monsoon seasons. Given their unique biology, these fish have emerged as a model taxon in several biological disciplines. Their increasing popularity stems from the extremely short lifespan that is the result of their specific life-history adaptations and is retained under laboratory conditions. Nothobranchius furzeri, the most popular laboratory species, is the vertebrate species with the shortest lifespan recorded in captivity. In the laboratory, adults of different Nothobranchius species and populations live between 3 and 18 months and, notably, there is a negative correlation between the captive lifespan of a species and the aridity of their habitat. Their short lifespan is coupled to rapid age-dependent functional decline and expression of cellular and molecular changes comparable to those observed in other vertebrates, including humans. The recent development of transgenesis in this species makes it possible to insert specific constructs into their genome, and the establishment of transgenic lines is facilitated by their very rapid generation time, which can be as short as 1 month. This makes Nothobranchius species particularly suited for investigating biological and molecular aspects of ageing and ageing-associated dysfunctions. At the same time, they also represent a unique model taxon to investigate the evolution of life-history adaptations and their genetic architecture. We review their natural history, including phylogenetic relationships, distribution in relation to habitat conditions and natural selection for differential longevity, population structure and demography, and life cycle with emphasis on diapause that may occur at three stages during embryonic development. We further critically evaluate their use as a laboratory model for understanding the evolution of a rapid ageing rate and its consequences for other life-history traits, for cellular, molecular and integrative traits associated with the ageing process, high incidence of neoplasias, their utility for genome-wide gene-expression studies, and as a model for quantitative genetics. We summarize recent achievements in fostering Nothobranchius species as a widely applicable model system, including an annotated transcriptome, successful transgenesis, and existence of viable inbred lines. We compare the conditions they experience in the wild and in captivity and suggest that they are an ideal taxon to investigate natural genetic variation in a laboratory setting. We conclude that Nothobranchius species - and N. furzeri in particular - could become a unique model taxon that bridges interests in ecological and biomedical research. We hope that a conceptual and methodological integration of these two branches of biology will provide important new insights.

Turquoise killifish.

Reichard et al. introduce the turquoise killifish (Nothobranchius furzeri), notable for its short-life span and diapause stage.