Disruption of tRNA biogenesis enhances proteostatic resilience, improves later-life health, and promotes longevity.

tRNAs are evolutionarily ancient molecular decoders essential for protein translation. In eukaryotes, tRNAs and other short, noncoding RNAs are transcribed by RNA polymerase (Pol) III, an enzyme that promotes ageing in yeast, worms, and flies. Here, we show that a partial reduction in Pol III activity specifically disrupts tRNA levels.

Understanding exogenous factors and biological mechanisms for cognitive frailty: A multidisciplinary scoping review.

Cognitive frailty (CF) is the conjunction of cognitive impairment without dementia and physical frailty. While predictors of each element are well-researched, mechanisms of their co-occurrence have not been integrated, particularly in terms of relationships between social, psychological, and biological factors. This interdisciplinary scoping review set out to categorise a heterogenous multidisciplinary literature to identify potential pathways and mechanisms of CF, and research gaps.

Corrigendum: Reduced insulin signaling targeted to serotonergic neurons but not other neuronal subtypes extends lifespan in .

[This corrects the article DOI: 10.3389/fnagi.2022.

Response to thermal and infection stresses in an American vector of visceral leishmaniasis.

Lutzomyia longipalpis is known as one of the primary insect vectors of visceral leishmaniasis. For such ectothermic organisms, the ambient temperature is a critical life factor. However, the impact of temperature has been ignored in many induced-stress situations of the vector life.

Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in .

Reduced Insulin/IGF-like signaling (IIS) plays an evolutionarily conserved role in improving longevity and some measures of health-span in model organisms. Recent studies, however, have found a disconnection between lifespan extension and behavioral health-span. We have previously shown that reduction of IIS in neurons extends female lifespan but does not improve negative geotaxis senescence and has a detrimental effect on exploratory walking senescence in both sexes.

Altered medial prefrontal cortex and dorsal raphé activity predict genotype and correlate with abnormal learning behavior in a mouse model of autism-associated 2p16.3 deletion.

2p16.3 deletion, involving NEUREXIN1 (NRXN1) heterozygous deletion, substantially increases the risk of developing autism and other neurodevelopmental disorders. We have a poor understanding of how NRXN1 heterozygosity impacts on brain function and cognition to increase the risk of developing the disorder.

Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity.

Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly.

Ketamine Restores Thalamic-Prefrontal Cortex Functional Connectivity in a Mouse Model of Neurodevelopmental Disorder-Associated 2p16.3 Deletion.

2p16.3 deletions, involving heterozygous NEUREXIN1 (NRXN1) deletion, dramatically increase the risk of developing neurodevelopmental disorders, including autism and schizophrenia. We have little understanding of how NRXN1 heterozygosity increases the risk of developing these disorders, particularly in terms of the impact on brain and neurotransmitter system function and brain network connectivity.

Loss of angiotensin-converting enzyme-related (ACER) peptidase disrupts behavioural and metabolic responses to diet in .

() encodes a member of the angiotensin-converting enzyme (ACE) family of metallopeptidases that in mammals play roles in the endocrine regulation of blood homeostasis. ACE is also expressed in adipose tissue, where it is thought to play a role in metabolic regulation. ACER is expressed in the adult fat body of the head and abdomen and is secreted into the haemolymph.

Behavioral Senescence and Aging-Related Changes in Motor Neurons and Brain Neuromodulator Levels Are Ameliorated by Lifespan-Extending Reproductive Dormancy in .

The lifespan of can be extended substantially by inducing reproductive dormancy (also known as diapause) by lowered temperature and short days. This increase of longevity is accompanied by lowered metabolism and increased stress tolerance. We ask here whether behavioral senescence is ameliorated during adult dormancy.

The Drosophila insulin receptor independently modulates lifespan and locomotor senescence.

The Insulin/IGF-like signalling (IIS) pathway plays an evolutionarily conserved role in ageing. In model organisms reduced IIS extends lifespan and ameliorates some forms of functional senescence. However, little is known about IIS in nervous system ageing and behavioural senescence.

Cell-nonautonomous effects of dFOXO/DAF-16 in aging.

Drosophila melanogaster and Caenorhabditis elegans each carry a single representative of the Forkhead box O (FoxO) family of transcription factors, dFOXO and DAF-16, respectively. Both are required for lifespan extension by reduced insulin/Igf signaling, and their activation in key tissues can extend lifespan. Aging of these tissues may limit lifespan.

Molecular evolution and functional characterization of Drosophila insulin-like peptides.

Multicellular animals match costly activities, such as growth and reproduction, to the environment through nutrient-sensing pathways. The insulin/IGF signaling (IIS) pathway plays key roles in growth, metabolism, stress resistance, reproduction, and longevity in diverse organisms including mammals. Invertebrate genomes often contain multiple genes encoding insulin-like ligands, including seven Drosophila insulin-like peptides (DILPs).

DILP-producing median neurosecretory cells in the Drosophila brain mediate the response of lifespan to nutrition.

Dietary restriction extends lifespan in diverse organisms, but the gene regulatory mechanisms and tissues mediating the increased survival are still unclear. Studies in worms and flies have revealed a number of candidate mechanisms, including the target of rapamycin and insulin/IGF-like signalling (IIS) pathways and suggested a specific role for the nervous system in mediating the response. A pair of sensory neurons in Caenorhabditis elegans has been found to specifically mediate DR lifespan extension, but a neuronal focus in the Drosophila nervous system has not yet been identified.

The endosymbiont Wolbachia increases insulin/IGF-like signalling in Drosophila.

Insulin/IGF-like signalling (IIS) is an evolutionarily conserved pathway that has diverse functions in multi-cellular organisms. Mutations that reduce IIS can have pleiotropic effects on growth, development, metabolic homeostasis, fecundity, stress resistance and lifespan. IIS is also modified by extrinsic factors.

Insulin/IGF-like signalling, the central nervous system and aging.

Enormous strides in understanding aging have come from the discovery that mutations in single genes can extend healthy life-span in laboratory model organisms such as the yeast Saccharomyces, the fruit fly Drosophila melanogaster, the nematode worm Caenorhabditis elegans and the mouse. IIS [insulin/IGF (insulin-like growth factor)-like signalling] stands out as an important, evolutionarily conserved pathway involved in the determination of lifespan. The pathway has diverse functions in multicellular organisms, and mutations in IIS can affect growth, development, metabolic homoeostasis, fecundity and stress resistance, as well as lifespan.

Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs.

The insulin/IGF-like signalling (IIS) pathway has diverse functions in all multicellular organisms, including determination of lifespan. The seven insulin-like peptides (DILPs) in Drosophila are expressed in a stage- and tissue-specific manner. Partial ablation of the median neurosecretory cells (mNSCs) in the brain, which produce three DILPs, extends lifespan, reduces fecundity, alters lipid and carbohydrate metabolism and increases oxidative stress resistance.

Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands.

The insulin/insulin-like growth factor-like signaling pathway, present in all multicellular organisms, regulates diverse functions including growth, development, fecundity, metabolic homeostasis, and lifespan. In flies, ligands of the insulin/insulin-like growth factor-like signaling pathway, the Drosophila insulin-like peptides, regulate growth and hemolymph carbohydrate homeostasis during development and are expressed in a stage- and tissue-specific manner. Here, we show that ablation of Drosophila insulin-like peptide-producing median neurosecretory cells in the brain leads to increased fasting glucose levels in the hemolymph of adults similar to that found in diabetic mammals.

Excitatory and inhibitory switches for courtship in the brain of Drosophila melanogaster.

Background: Courtship is the best-studied behavior in Drosophila melanogaster, and work on its anatomical basis has concentrated mainly on the functional identification of sexually dimorphic sites in the brain. Much less is known of the more expansive, nondimorphic, but nonetheless essential, neural elements subserving male courtship behavior.

Results: Sites in the CNS mediating initiation and early steps of male courtship in Drosophila melanogaster were identified by analyzing the behavior of mosaic flies expressing transgenes designed either to suppress neurotransmission or enhance neuronal excitability.

Conditioning deficits of CaM-kinase transgenic Drosophila melanogaster in a new excitatory courtship assay.

Courtship suppression is an associative conditioning procedure in Drosophila melanogaster that is ethologically based and capable of being tested on individual flies. We have expanded the range of the courtship conditioning by developing an excitatory procedure in which male flies learn to associate a novel odor with the courtship stimulating cues of virgin females. Wild-type males normally court other mature males very little, but following training, the odor alone is able to elicit increased levels of courtship towards an object male.