Molecular evolutionary patterns of NAD+/Sirtuin aging signaling pathway across taxa

Gaur, Uma; Tu, Jianbo; Li, Diyan; Gao, Yue; Lian, Ting; Sun, Boyuan; Yang, Dapeng; Fan, Xiaolan; Yang, Mingyao

doi:10.1371/journal.pone.0182306

Cited by 9 publications

(9 citation statements)

References 59 publications

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“…Recent work on the comparative genomics of the p53 molecular network provided evidence of positive selection on genes within p53 networks of reptile (both ecto-and endothermic) relative to mammals, with reptiles having more positive selection on upstream genes (p53 and its regulators), especially in lizards and snakes (Passow et al, 2019). This is in contrast to the purifying selection on p53 across mammals (Gaur et al, 2017;Passow et al, 2019), with the exception of the branch leading to elephants (Passow et al, 2019). We also found that species with longer lifespans experienced less variation in selection across the p53 network, whereas those with shorter lifespans were equally likely to have both positive and purifying selection (Passow et al, 2019).…”

Section: Molecular Network For Cellular Senescence: P53/p16mentioning

confidence: 99%

The untapped potential of reptile biodiversity for understanding how and why animals age

et al. 2019

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1. The field of comparative ageing biology has greatly expanded in the past 20 years.Longitudinal studies of populations of reptiles with a range of maximum lifespans have accumulated and been analysed for evidence of mortality senescence and reproductive decline. While not as well represented in studies of amniote senescence, reptiles have been the subjects of many recent demographic and mechanistic studies of the biology of ageing.2. We review recent literature on reptile demographic senescence, mechanisms of senescence, and identify unanswered questions. Given the ecophysiological and demographic diversity of reptiles, what is the expected range of reptile senescence rates? Are known mechanisms of ageing in reptiles consistent with canonical hallmarks of ageing in model systems? What are the knowledge gaps in our understanding of reptile ageing? 3. We find ample evidence of increasing mortality with advancing age in many reptiles. Testudines stand out as slower ageing than other orders, but data on crocodilians and tuatara are sparse. Sex-specific analyses are generally not available.Studies of female reproduction suggest that reptiles are less likely to have reproductive decline with advancing age than mammals. 4. Reptiles share many physiological and molecular pathways of ageing with mammals, birds and laboratory model organisms. Adaptations related to stress physiology coupled with reptilian ectothermy suggest novel comparisons and contrasts that can be made with canonical ageing phenotypes in mammals. These include stem cell and regeneration biology, homeostatic mechanisms, IIS/TOR signalling, and DNA repair. 5. To overcome challenges to the study of reptile ageing, we recommend extending and expanding long-term monitoring of reptile populations, developing reptile cell lines to aid cellular biology, conducting more comparative studies of reptile morphology and physiology sampled along relevant life-history axes and sequencing more reptile genomes for comparative genomics. Given the diversity of reptile life histories and adaptations, achieving these directives will likely greatly benefit all ageing biology.

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Section: Molecular Network For Cellular Senescence: P53/p16mentioning

confidence: 99%

The untapped potential of reptile biodiversity for understanding how and why animals age

et al. 2019

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“…Past research has identified evidence of positive selection across genes and pathways associated with apoptosis and cancer in mammals (Crespi and Summers 2006; Kosiol et al. 2008; Gaur et al. 2017).…”

Section: Discussionmentioning

confidence: 99%

Contrasting Patterns of Rapid Molecular Evolution within thep53Network across Mammal and Sauropsid Lineages

Passow

Bronikowski

Blackmon

et al. 2019

Genome Biology and Evolution

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Cancer is a threat to multicellular organisms, yet the molecular evolution of pathways that prevent the accumulation of genetic damage has been largely unexplored. The p53 network regulates how cells respond to DNA-damaging stressors. We know little about p53 network molecular evolution as a whole. In this study, we performed comparative genetic analyses of the p53 network to quantify the number of genes within the network that are rapidly evolving and constrained, and the association between lifespan and the patterns of evolution. Based on our previous published data set, we used genomes and transcriptomes of 34 sauropsids and 32 mammals to analyze the molecular evolution of 45 genes within the p53 network. We found that genes in the network exhibited evidence of positive selection and divergent molecular evolution in mammals and sauropsids. Specifically, we found more evidence of positive selection in sauropsids than mammals, indicating that sauropsids have different targets of selection. In sauropsids, more genes upstream in the network exhibited positive selection, and this observation is driven by positive selection in squamates, which is consistent with previous work showing rapid divergence and adaptation of metabolic and stress pathways in this group. Finally, we identified a negative correlation between maximum lifespan and the number of genes with evidence of divergent molecular evolution, indicating that species with longer lifespans likely experienced less variation in selection across the network. In summary, our study offers evidence that comparative genomic approaches can provide insights into how molecular networks have evolved across diverse species.

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“…In this case, treating AD with mTOR as the target, the timing of medication may be a crucial factor. Furthermore, the side effects of rapamycin and its analogue cannot be ignored, like reduced fertility and impaired locomotor activity [86]. Additionally, further research is needed to examine the beneficial effects of rapamycin in AD flies before deciding whether it can be a potential drug for clinical treatment of AD.…”

Section: Mtor Signaling Pathwaymentioning

confidence: 99%

Pharmacological Treatment of Alzheimer’s Disease: Insights from Drosophila melanogaster

Cheng

Song

et al. 2020

IJMS

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Aging is an ineluctable law of life. During the process of aging, the occurrence of neurodegenerative disorders is prevalent in the elderly population and the predominant type of dementia is Alzheimer’s disease (AD). The clinical symptoms of AD include progressive memory loss and impairment of cognitive functions that interfere with daily life activities. The predominant neuropathological features in AD are extracellular β-amyloid (Aβ) plaque deposition and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated Tau. Because of its complex pathobiology, some tangible treatment can only ameliorate the symptoms, but not prevent the disease altogether. Numerous drugs during pre-clinical or clinical studies have shown no positive effect on the disease outcome. Therefore, understanding the basic pathophysiological mechanism of AD is imperative for the rational design of drugs that can be used to prevent this disease. Drosophila melanogaster has emerged as a highly efficient model system to explore the pathogenesis and treatment of AD. In this review we have summarized recent advancements in the pharmacological research on AD using Drosophila as a model species, discussed feasible treatment strategies and provided further reference for the mechanistic study and treatment of age-related AD.

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Molecular evolutionary patterns of NAD+/Sirtuin aging signaling pathway across taxa

Cited by 9 publications

References 59 publications

The untapped potential of reptile biodiversity for understanding how and why animals age

The untapped potential of reptile biodiversity for understanding how and why animals age

Contrasting Patterns of Rapid Molecular Evolution within thep53Network across Mammal and Sauropsid Lineages

Pharmacological Treatment of Alzheimer’s Disease: Insights from Drosophila melanogaster

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