Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles about aging.
Title: piRNAs regulate a Hedgehog germline-to-soma pro-aging signal
Authors: Cheng Shi, Coleen T. Murphy
Type: Research Article
The reproductive system regulates somatic aging through competing anti- and pro-aging signals. Germline removal extends somatic lifespan through conserved pathways including insulin and mammalian target-of-rapamycin signaling, while germline hyperactivity shortens lifespan through unknown mechanisms. Here we show that mating-induced germline hyperactivity downregulates piRNAs, in turn desilencing their targets, including the Hedgehog-like ligand-encoding genes wrt-1 and wrt-10, ultimately causing somatic collapse and death. Germline-produced Hedgehog signals require PTR-6 and PTR-16 receptors for mating-induced shrinking and death. Our results reveal an unconventional role of the piRNA pathway in transcriptional regulation of Hedgehog signaling and a new role of Hedgehog signaling in the regulation of longevity and somatic maintenance: Hedgehog signaling is controlled by the tunable piRNA pathway to encode the previously unknown germline-to-soma pro-aging signal. Mating-induced piRNA downregulation in the germline and subsequent Hedgehog signaling to the soma enable the animal to tune somatic resource allocation to germline needs, optimizing reproductive timing and survival.
Access this article: https://doi.org/10.1038/s43587-022-00329-2
Title: Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics
Authors: Yeaeun Han, Sung Young Kim
Senescence compromises the essential role that the endothelium plays in maintaining vascular homeostasis, so promoting endothelial dysfunction and the development of age-related vascular diseases. Their biological and clinical significance calls for strategies for identifying and therapeutically targeting senescent endothelial cells. While senescence and endothelial dysfunction have been studied extensively, distinguishing what is distinctly endothelial senescence remains a barrier to overcome for an effective approach to addressing it. Here, we review the mechanisms underlying endothelial senescence and the evidence for its clinical importance. Furthermore, we discuss the current state and the limitations in the approaches for the detection and therapeutic intervention of target cells, suggesting potential directions for future research.
Access this article: https://doi.org/10.1038/s12276-022-00906-w
Title: Neuroprosthetics: from sensorimotor to cognitive disorders
Authors: Ankur Gupta, Nikolaos Vardalakis, Fabien B. Wagner
Neuroprosthetics is a multidisciplinary field at the interface between neurosciences and biomedical engineering, which aims at replacing or modulating parts of the nervous system that get disrupted in neurological disorders or after injury. Although neuroprostheses have steadily evolved over the past 60 years in the field of sensory and motor disorders, their application to higher-order cognitive functions is still at a relatively preliminary stage. Nevertheless, a recent series of proof-of-concept studies suggest that electrical neuromodulation strategies might also be useful in alleviating some cognitive and memory deficits, in particular in the context of dementia. Here, we review the evolution of neuroprosthetics from sensorimotor to cognitive disorders, highlighting important common principles such as the need for neuroprosthetic systems that enable multisite bidirectional interactions with the nervous system.
Access this article: https://doi.org/10.1038/s42003-022-04390-w
Title: Single-cell-led drug repurposing for Alzheimer's disease
Authors: Silvia Parolo, Federica Mariotti, Pranami Bora, Lucia Carboni, Enrico Domenici
Type: Research Article
Alzheimer's disease is the most common form of dementia. Notwithstanding the huge investments in drug development, only one disease-modifying treatment has been recently approved. Here we present a single-cell-led systems biology pipeline for the identification of drug repurposing candidates. Using single-cell RNA sequencing data of brain tissues from patients with Alzheimer's disease, genome-wide association study results, and multiple gene annotation resources, we built a multi-cellular Alzheimer's disease molecular network that we leveraged for gaining cell-specific insights into Alzheimer's disease pathophysiology and for the identification of drug repurposing candidates. Our computational approach pointed out 54 candidate drugs, mainly targeting MAPK and IGF1R signaling pathways, which could be further evaluated for their potential as Alzheimer’s disease therapy.
Access this article: https://doi.org/10.1038/s41598-023-27420-x
Title: Both age and social environment shape the phenotype of ant workers
Authors: Martin Quque, Charlotte Brun, Claire Villette, Cédric Sueur, François Criscuolo, Dimitri Heintz, Fabrice Bertile
Type: Research Article
Position within the social group has consequences on individual lifespans in diverse taxa. This is especially obvious in eusocial insects, where workers differ in both the tasks they perform and their aging rates. However, in eusocial wasps, bees and ants, the performed task usually depends strongly on age. As such, untangling the effects of social role and age on worker physiology is a key step towards understanding the coevolution of sociality and aging. We performed an experimental protocol that allowed a separate analysis of these two factors using four groups of black garden ant (Lasius niger) workers: young foragers, old foragers, young nest workers, and old nest workers. We highlighted age-related differences in the proteome and metabolome of workers that were primarily related to worker subcaste and only secondarily to age. The relative abundance of proteins and metabolites suggests an improved xenobiotic detoxification, and a fuel metabolism based more on lipid use than carbohydrate use in young ants, regardless of their social role. Regardless of age, proteins related to the digestive function were more abundant in nest workers than in foragers. Old foragers were mostly characterized by weak abundances of molecules with an antibiotic activity or involved in chemical communication. Finally, our results suggest that even in tiny insects, extended lifespan may require to mitigate cancer risks. This is consistent with results found in eusocial rodents and thus opens up the discussion of shared mechanisms among distant taxa and the influence of sociality on life history traits such as longevity.
Access this article: https://doi.org/10.1038/s41598-022-26515-1