Bats as instructive animal models for studying longevity and aging.

Bats (order Chiroptera) are emerging as instructive animal models for aging studies. Unlike some common laboratory species, they meet a central criterion for aging studies: they live for a long time in the wild or in captivity, for 20, 30, and even >40 years. Healthy aging (i.e., healthspan) in bats has drawn attention to their potential to improve the lives of aging humans due to bat imperviousness to viral infections, apparent low rate of tumorigenesis, and unique ability to repair DNA. At the same time, bat longevity also permits the accumulation of age-associated systemic pathologies that can be examined in detail and manipulated, especially in captive animals. Research has uncovered additional and critical advantages of bats. In multiple ways, bats are better analogs to humans than are rodents. In this review, we highlight eight diverse areas of bat research with relevance to aging: genome sequencing, telomeres, and DNA repair; immunity and inflammation; hearing; menstruation and menopause; skeletal system and fragility; neurobiology and neurodegeneration; stem cells; and senescence and mortality. These examples demonstrate the broad relevance of the bat as an animal model and point to directions that are particularly important for human aging studies.

The genome sequence of Molossus alvarezi González-Ruiz, Ramírez-Pulido and Arroyo-Cabrales, 2011 (Chiroptera, Molossidae).

We present a genome assembly from an individual female Molossus alvarezi (Chordata; Mammalia; Chiroptera; Molossidae). The genome sequence is 2.490 Gb in span. The majority of the assembly is scaffolded into 24 chromosomal pseudomolecules, with the X sex chromosomes assembled.

Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity.

The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan.

The genome sequence of Rhynchonycteris naso, Peters, 1867 (Chiroptera, Emballonuridae, Rhynchonycteris).

We present a reference genome assembly from an individual male Rhynchonycteris naso (Chordata; Mammalia; Chiroptera; Emballonuridae). The genome sequence is 2.46 Gb in span. The majority of the assembly is scaffolded into 22 chromosomal pseudomolecules, with the Y sex chromosome assembled.

The genome sequence of the particolored bat, Vespertilio murinus Linnaeus, 1758.

We present a genome assembly from an individual male Vespertilio murinus (the particolored bat; Chordata; Mammalia; Chiroptera; Vespertilionidae). The genome sequence is 1,925.6 megabases in span. Most of the assembly is scaffolded into 20 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.96 kilobases in length.

The genome sequence of the endemic Mexican common mustached Bat, Pteronotus mexicanus. Miller, 1902 [Mormoopidae; Pteronotus].

We describe here the first characterization of the genome of the bat Pteronotus mexicanus, an endemic species of Mexico, as part of the Mexican Bat Genome Project which focuses on the characterization and assembly of the genomes of endemic bats in Mexico. The genome was assembled from a liver tissue sample of an adult male from Jalisco, Mexico provided by the Texas Tech University Museum tissue collection. The assembled genome size was 1.9 Gb. The assembly of the genome was fitted in a framework of 110,533 scaffolds and 1,659,535 contigs. The ecological importance of bats such as P. mexicanus, and their diverse ecological roles, underscores the value of having complete genomes in addressing information gaps and facing challenges regarding their function in ecosystems and their conservation.

The genome sequence of the Brown Long-eared bat, Plecotus auritus (Linnaeus 1758).

We present a genome assembly from a female Plecotus auritus (Brown Long-eared bat; Chordata; Mammalia; Chiroptera; Vespertilionidae). The genome sequence is 2163.2 megabases in span. Most of the assembly is scaffolded into 16 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.91 kilobases in length.

The genome sequence of Daubenton's bat, Myotis daubentonii (Kuhl, 1817).

We present a genome assembly from an individual male Myotis daubentonii (Daubenton's bat; Chordata; Mammalia; Chiroptera; Vespertilionidae). The genome sequence is 2,127.8 megabases in span. Most of the assembly is scaffolded into 23 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 17.34 kilobases in length.

The genome sequence of Tadarida brasiliensis I. Geoffroy Saint-Hilaire, 1824 [Molossidae; Tadarida].

We present a genome assembly from an individual male Tadarida brasiliensis (The Brazilian free-tailed bat; Chordata; Mammalia; Chiroptera; Molossidae). The genome sequence is 2.28 Gb in span. The majority of the assembly is scaffolded into 25 chromosomal pseudomolecules, with the X and Y sex chromosomes assembled.

Karyotypic stasis and swarming influenced the evolution of viral tolerance in a species-rich bat radiation.

The emergence of COVID-19 and severe acute respiratory syndrome (SARS) has prioritized understanding bats' viral tolerance. Myotis bats are exceptionally species rich and have evolved viral tolerance. They also exhibit swarming, a cryptic behavior where large, multi-species assemblages gather for mating, which has been hypothesized to promote interspecific hybridization. To resolve the coevolution of genome architecture and their unusual antiviral tolerance, we undertook a phylogenomic analysis of 60 Old World Myotis genomes. We demonstrate an extensive history of introgressive hybridization that has replaced the species phylogeny across 17%-93% of the genome except for pericentromeric regions of macrochromosomes. Introgression tracts were enriched on microchromosome regions containing key antiviral pathway genes overexpressed during viral challenge experiments. Together, these results suggest that the unusual Myotis karyotype may have evolved to selectively position immune-related genes in high recombining genomic regions prone to introgression of divergent alleles, including a diversity of interleukin loci responsible for the release of pro-inflammatory cytokines.

Comparative Genome Microsynteny Illuminates the Fast Evolution of Nuclear Mitochondrial Segments (NUMTs) in Mammals.

The escape of DNA from mitochondria into the nuclear genome (nuclear mitochondrial DNA, NUMT) is an ongoing process. Although pervasively observed in eukaryotic genomes, their evolutionary trajectories in a mammal-wide context are poorly understood. The main challenge lies in the orthology assignment of NUMTs across species due to their fast evolution and chromosomal rearrangements over the past 200 million years. To address this issue, we systematically investigated the characteristics of NUMT insertions in 45 mammalian genomes and established a novel, synteny-based method to accurately predict orthologous NUMTs and ascertain their evolution across mammals. With a series of comparative analyses across taxa, we revealed that NUMTs may originate from nonrandom regions in mtDNA, are likely found in transposon-rich and intergenic regions, and unlikely code for functional proteins. Using our synteny-based approach, we leveraged 630 pairwise comparisons of genome-wide microsynteny and predicted the NUMT orthology relationships across 36 mammals. With the phylogenetic patterns of NUMT presence-and-absence across taxa, we constructed the ancestral state of NUMTs given the mammal tree using a coalescent method. We found support on the ancestral node of Fereuungulata within Laurasiatheria, whose subordinal relationships are still controversial. This study broadens our knowledge on NUMT insertion and evolution in mammalian genomes and highlights the merit of NUMTs as alternative genetic markers in phylogenetic inference.

Hibernation telomere dynamics in a shifting climate: insights from wild greater horseshoe bats.

Hibernation is linked with various hypotheses to explain the extended lifespan of hibernating mammals compared with their non-hibernating counterparts. Studies on telomeres, markers of ageing and somatic maintenance, suggest telomere shortening slows during hibernation, and lengthening may reflect self-maintenance with favourable conditions. Bats in temperate zones adjust body temperatures during winter torpor to conserve energy and exploit mild conditions for foraging. Climate change may impact the hibernation cycle of bats, but more research is needed regarding the role of telomeres in understanding their response to a changing climate. Here, relative telomere length (rTL) was measured in the long-lived greater horseshoe bat Rhinolophus ferrumequinum (n = 223 individuals) over three winters, considering climatic conditions. Cross-sectional analyses revealed between-individual variation in rTL with a strong year effect, likely linked to varying weather conditions and foraging success. Additionally, within-individual increases of rTL occurred in 51% of consecutive measurements, with evidence of increasing telomerase expression during hibernation in this species. These findings highlight the beneficial effects of hibernation on telomeres and potential consequences of changing climatic conditions for long-lived temperate bats. Understanding the interplay between hibernation, telomeres, and climate can provide insights into the adaptive capacity and survival of bat populations facing environmental challenges.

The genome sequence of Molossusnigricans (Chiroptera, Molossidae; Miller, 1902).

We present a genome assembly from an individual male Molossus nigricans (Chordata; Mammalia; Chiroptera; Molossidae). The genome sequence is 2.41 gigabases in span. The majority of the assembly is scaffolded into 24 chromosomal pseudomolecules, with the X sex chromosome assembled.

Comparison of antiviral responses in two bat species reveals conserved and divergent innate immune pathways.

Bats host a range of disease-causing viruses without displaying clinical symptoms. The mechanisms behind this are a continuous source of interest. Here, we studied the antiviral response in the Egyptian fruit bat and Kuhl's pipistrelle, representing two subordinal clades. We profiled the antiviral response in fibroblasts using RNA sequencing and compared bat with primate and rodent responses. Both bats upregulate similar genes; however, a subset of these genes is transcriptionally divergent between them. These divergent genes also evolve rapidly in sequence, have specific promoter architectures, and are associated with programs underlying tolerance and resistance. Finally, we characterized antiviral genes that expanded in bats, with duplicates diverging in sequence and expression. Our study reveals a largely conserved antiviral program across bats and points to a set of genes that rapidly evolve through multiple mechanisms. These can contribute to bat adaptation to viral infection and provide directions to understanding the mechanisms behind it.

Expanding evolutionary theories of ageing to better account for symbioses and interactions throughout the Web of Life.

How, when, and why organisms age are fascinating issues that can only be fully addressed by adopting an evolutionary perspective. Consistently, the main evolutionary theories of ageing, namely the Mutation Accumulation theory, the Antagonistic Pleiotropy theory, and the Disposable Soma theory, have formulated stimulating hypotheses that structure current debates on both the proximal and ultimate causes of organismal ageing. However, all these theories leave a common area of biology relatively under-explored. The Mutation Accumulation theory and the Antagonistic Pleiotropy theory were developed under the traditional framework of population genetics, and therefore are logically centred on the ageing of individuals within a population. The Disposable Soma theory, based on principles of optimising physiology, mainly explains ageing within a species. Consequently, current leading evolutionary theories of ageing do not explicitly model the countless interspecific and ecological interactions, such as symbioses and host-microbiomes associations, increasingly recognized to shape organismal evolution across the Web of Life. Moreover, the development of network modelling supporting a deeper understanding on the molecular interactions associated with ageing within and between organisms is also bringing forward new questions regarding how and why molecular pathways associated with ageing evolved. Here, we take an evolutionary perspective to examine the effects of organismal interactions on ageing across different levels of biological organisation, and consider the impact of surrounding and nested systems on organismal ageing. We also apply this perspective to suggest open issues with potential to expand the standard evolutionary theories of ageing.

Chiropterans Are a Hotspot for Horizontal Transfer of DNA Transposons in Mammalia.

Horizontal transfer of transposable elements (TEs) is an important mechanism contributing to genetic diversity and innovation. Bats (order Chiroptera) have repeatedly been shown to experience horizontal transfer of TEs at what appears to be a high rate compared with other mammals. We investigated the occurrence of horizontally transferred (HT) DNA transposons involving bats. We found over 200 putative HT elements within bats; 16 transposons were shared across distantly related mammalian clades, and 2 other elements were shared with a fish and two lizard species. Our results indicate that bats are a hotspot for horizontal transfer of DNA transposons. These events broadly coincide with the diversification of several bat clades, supporting the hypothesis that DNA transposon invasions have contributed to genetic diversification of bats.

Bat pluripotent stem cells reveal unusual entanglement between host and viruses.

Bats are distinctive among mammals due to their ability to fly, use laryngeal echolocation, and tolerate viruses. However, there are currently no reliable cellular models for studying bat biology or their response to viral infections. Here, we created induced pluripotent stem cells (iPSCs) from two species of bats: the wild greater horseshoe bat (Rhinolophus ferrumequinum) and the greater mouse-eared bat (Myotis myotis). The iPSCs from both bat species showed similar characteristics and had a gene expression profile resembling that of cells attacked by viruses. They also had a high number of endogenous viral sequences, particularly retroviruses. These results suggest that bats have evolved mechanisms to tolerate a large load of viral sequences and may have a more intertwined relationship with viruses than previously thought. Further study of bat iPSCs and their differentiated progeny will provide insights into bat biology, virus host relationships, and the molecular basis of bats' special traits.

The genome sequence of the northern bat, Eptesicus nilssonii (Keyserling & Blasius, 1839).

We present a genome assembly from an individual Eptesicus nilssonii (the northern bat; Chordata; Mammalia; Chiroptera; Vespertilionidae), derived from the placental tissue of a pregnancy that resulted a male pup. The genome sequence is 2,064.1 megabases in span. Most of the assembly is scaffolded into 26 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 17.04 kilobases in length.

The genome sequence of the Soprano Pipistrelle, Pipistrellus pygmaeus (Leach, 1825).

We present a genome assembly from an individual male Pipistrellus pygmaeus (the Soprano Pipistrelle; Chordata; Mammalia; Chiroptera; Vespertilionidae). The genome sequence is 1,895.1 megabases in span. Most of the assembly is scaffolded into 23 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 17.18 kilobases in length.