Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing

Jebb, David; Foley, Nicole M.; Whelan, Conor V.; Touzalin, Frédéric; Puechmaille, Sébastien J.; Teeling, Emma C.

doi:10.1038/s41598-018-31093-2

Cited by 26 publications

(21 citation statements)

References 82 publications

(95 reference statements)

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“…As more bat reagents become available in the future, it should be possible to elucidate the mechanisms that bats have evolved to coexist with viruses in the absence of disease and this information could be useful for preventing or treating lethal viral infections in humans (55,154).…”

Section: Resultsmentioning

confidence: 99%

Novel Insights Into Immune Systems of Bats

et al. 2020

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In recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. These include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as Ebola virus disease, Marburg haemorrhagic fever and severe acute respiratory syndrome (SARS) in humans. The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses. Here, we summarize our current understanding of antiviral immune responses in bats and discuss their ability to co-exist with emerging viruses that cause serious disease in other mammals. We highlight how this knowledge may help us to predict viral spillovers into new hosts and discuss future directions for the field.

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Section: Resultsmentioning

confidence: 99%

Novel Insights Into Immune Systems of Bats

et al. 2020

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“…Logistically it is difficult to study bats in an ageing context, as most are only found in the wild and not easily maintained in captivity 11 . Initial longitudinal ageing studies suggest that the longest-lived genus (Myotis) maintains the length of their telomeres with age without developing cancer 12 and do not show an increased level of mitochondrial damage as expected given their metabolic rate 13 . This is potentially due to adaptations in their DNA repair and maintenance mechanisms 13 .…”

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confidence: 90%

Longitudinal comparative transcriptomics reveals unique mechanisms underlying extended healthspan in bats

Huang¹,

Whelan²,

Foley³

et al. 2019

Nat Ecol Evol

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Bats are the longest-lived mammals, given their body size. However, the underlying molecular mechanisms of their extended healthspans are poorly understood. To address this question we carried out an eight-year longitudinal study of ageing in longlived bats (Myotis myotis). We deep-sequenced ~1.7 trillion base pairs of RNA from 150 blood samples collected from known aged bats to ascertain the age-related transcriptomic shifts and potential microRNA-directed regulation that occurred. We also compared ageing transcriptomic profiles between bats and other mammals by analysis of 298 longitudinal RNA sequencing datasets. Bats did not show the same transcriptomic changes with age as commonly observed in humans and other mammals, but rather exhibited a unique, age-related gene expression pattern associated with DNA repair, autophagy, immunity and tumour suppression that may drive their extended healthspans. We show that bats have naturally evolved transcriptomic signatures that are known to extend lifespan in model organisms, and identify novel genes not yet implicated in healthy ageing. We further show that bats' longevity profiles are partially regulated by microRNA, thus providing novel regulatory targets and pathways for future ageing intervention studies. These results further disentangle the ageing process by highlighting which ageing pathways contribute most to healthy ageing in mammals. Articles Nature ecology & evolutioN results and discussion Overview of M. myotis ageing transcriptomes. Using a non-lethal sampling process developed to maximize transcript representation from bat blood (>60% of all protein-coding genes represented) 23 , we deep-sequenced ~1.7 trillion base pairs of RNA from 100 bat blood samples (69.6 ± 9.0 s.d. million reads per sample) using Illumina RNA-sequencing (RNA-Seq). These blood samples (~50-200 μl) were collected from 70 individual bats ranging in age from 0 to >7 years (for example, first caught as an adult 6 years before subsequent recapture) at five colonies in Brittany, France (Supplementary Tables 1-3 and Supplementary Fig. 1). The majority of the raw reads (98.5%) showed high quality (>Q30). On average, 77% of clean reads were successfully mapped to the reference genome (Myotis lucifugus), 64.2% of which had unique mapping coordinates. Of all mapped reads, 88.1% were concordantly aligned. Only those reads that were uniquely and concordantly mapped were used for downstream analyses. To gain an overview of the bat blood tran

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“…It may well be an essential component in “inflammaging” [ 42 ]. There is some evidence that at least in some species of bat, mitochondrial health, despite bursts of oxidative stress, is maintained by stringent mitochondrial quality control mechanisms, like mitophagy [ 119 ]. Mitophagy is in fact a negative regulator of NLRP3 inflammasome activity, so although mitochondrial damage can activate the inflammasome, it can also activate counter-balancing mitophagy to prevent excessive inflammation [ 120 ].…”

Section: The Immune System Hormesis and Mitochondriamentioning

confidence: 99%

SARS-CoV-2 and mitochondrial health: implications of lifestyle and ageing

Nunn

Guy²,

Brysch

et al. 2020

Immun Ageing

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Infection with SARs-COV-2 displays increasing fatality with age and underlying co-morbidity, in particular, with markers of the metabolic syndrome and diabetes, which seems to be associated with a “cytokine storm” and an altered immune response. This suggests that a key contributory factor could be immunosenescence that is both age-related and lifestyle-induced. As the immune system itself is heavily reliant on mitochondrial function, then maintaining a healthy mitochondrial system may play a key role in resisting the virus, both directly, and indirectly by ensuring a good vaccine response. Furthermore, as viruses in general, and quite possibly this new virus, have also evolved to modulate immunometabolism and thus mitochondrial function to ensure their replication, this could further stress cellular bioenergetics. Unlike most sedentary modern humans, one of the natural hosts for the virus, the bat, has to “exercise” regularly to find food, which continually provides a powerful adaptive stimulus to maintain functional muscle and mitochondria. In effect the bat is exposed to regular hormetic stimuli, which could provide clues on how to resist this virus. In this paper we review the data that might support the idea that mitochondrial health, induced by a healthy lifestyle, could be a key factor in resisting the virus, and for those people who are perhaps not in optimal health, treatments that could support mitochondrial function might be pivotal to their long-term recovery.

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Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing

Cited by 26 publications

References 82 publications

Novel Insights Into Immune Systems of Bats

Novel Insights Into Immune Systems of Bats

Longitudinal comparative transcriptomics reveals unique mechanisms underlying extended healthspan in bats

SARS-CoV-2 and mitochondrial health: implications of lifestyle and ageing

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