Abstract
Most research on mechanisms of aging is being conducted in a very limited number of classical model species, i.e., laboratory mouse (Mus musculus), rat (Rattus norvegicus domestica), the common fruit fly (Drosophila melanogaster) and roundworm (Caenorhabditis elegans). The obvious advantages of using these models are access to resources such as strains with known genetic properties, high-quality genomic and transcriptomic sequencing data, versatile experimental manipulation capabilities including well-established genome editing tools, as well as extensive experience in husbandry. However, this approach may introduce interpretation biases due to the specific characteristics of the investigated species, which may lead to inappropriate, or even false, generalization. For example, it is still unclear to what extent knowledge of aging mechanisms gained in short-lived model organisms is transferable to long-lived species such as humans. In addition, other specific adaptations favoring a long and healthy life from the immense evolutionary toolbox may be entirely missed. In this review, we summarize the specific characteristics of emerging animal models that have attracted the attention of gerontologists, we provide an overview of the available data and resources related to these models, and we summarize important insights gained from them in recent years. The models presented include short-lived ones such as killifish (Nothobranchius furzeri), long-lived ones such as primates (Callithrix jacchus, Cebus imitator, Macaca mulatta), bathyergid mole-rats (Heterocephalus glaber, Fukomys spp.), bats (Myotis spp.), birds, olms (Proteus anguinus), turtles, greenland sharks, bivalves (Arctica islandica), and potentially non-aging ones such as Hydra and Planaria.
Highlights
Most of our current knowledge on mechanisms of aging has been acquired using classical model systems such as mouse (Mus musculus) and rat (Rattus norvegicus domestica) as well as the common fruit fly (Drosophila melanogaster) and roundworm (Caenorhabditis elegans)
Birds have an increased life expectancy, e.g., more than 50 years in the northern fulmar (Fulmarus glacialis), despite higher body temperatures, glucose levels and metabolic rates – as compared to size-matched mammalian species (Holmes and Ottinger, 2003; Harrison and Lightfoot, 2006; Furness and Speakman, 2008; Munshi-South and Wilkinson, 2010). This may be partially explained by their lower reactive oxygen species generation per unit O2 consumption and lower oxidative damage levels (Lambert et al, 2007), which has been attributed to reduced activity of mitochondrial complex I (Barja et al, 1994) and their uricotelic metabolism, as elevated levels of blood urates serve as natural antioxidants (Cooper-Mullin and McWilliams, 2016)
Similar to African mole-rats, blind mole rats (Spalax), e.g., are strong positive outliers from the lifespan to body mass correlation (Tacutu et al, 2018) and extremely cancer resistant – the latter possibly mediated by a concerted necrotic cell death mechanism (Gorbunova et al, 2012)
Summary
Most of our current knowledge on mechanisms of aging has been acquired using classical model systems such as mouse (Mus musculus) and rat (Rattus norvegicus domestica) as well as the common fruit fly (Drosophila melanogaster) and roundworm (Caenorhabditis elegans). Birds have an increased life expectancy, e.g., more than 50 years in the northern fulmar (Fulmarus glacialis), despite higher body temperatures, glucose levels and metabolic rates – as compared to size-matched mammalian species (Holmes and Ottinger, 2003; Harrison and Lightfoot, 2006; Furness and Speakman, 2008; Munshi-South and Wilkinson, 2010) This may be partially explained by their lower reactive oxygen species generation per unit O2 consumption and lower oxidative damage levels (Lambert et al, 2007), which has been attributed to reduced activity of mitochondrial complex I (Barja et al, 1994) and their uricotelic metabolism, as elevated levels of blood urates serve as natural antioxidants (Cooper-Mullin and McWilliams, 2016). A comparative genomic analysis of an endangered parrot species, the blue-fronted Amazon (Amazona aestiva) with 30 other bird species has identified longevity-associated genes under positive selection These are involved in various cellular functions, including telomerase activity, DNA damage repair, cell proliferation control, cancer, immunity as well as anti-oxidative mechanisms (Wirthlin et al, 2018). As with Hydra, one of the great challenges for the future will be to explore applications for transferring the knowledge gained in these invertebrates to humans
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