{"doi":"10.1093/sleep/zsad044","title":"Sleep problems in old age: metabotropic glutamate receptor to the rescue","abstract":"Many biological processes undergo an age-associated progressive decline, and sleep is no exception.Aging leads to several changes in sleep patterns, such as increased sleep latency, reduced slowwave sleep, and sleep fragmentation [1].Consistent with sleep's critical role in learning and memory, disrupted sleep in old age is accompanied by memory impairments and cognitive decline [2].Studies have revealed numerous molecular changes associated with aging [3-5], some of which are implicated in age-associated memory impairment [6, 7].However, the molecular mechanisms underlying sleep disturbances in old age and their role in memory impairment are poorly understood.Due to a short lifespan and conserved molecular mechanisms underlying sleep, memory, and aging, Drosophila is a valuable model for discovering molecular pathways underlying age-dependent sleep and memory decline [8-16].In this issue of SLEEP, Hou et al.[17] employed a small molecule screening approach to look for compounds that could enhance sleep in aged Drosophila.The authors first confirmed a previous finding that flies only 30 days old exhibited reduced and fragmented sleep [12], which are characteristics of age-associated sleep decline.This finding, along with an automated high-throughput sleep assay, made it feasible to screen 1280 small molecules to look for those that can rescue the age-dependent sleep decline.After multiple verification steps, the authors found that 3,3-difluorobenzaldazine (DFB), an allosteric enhancer of the metabotropic glutamate receptor (mGluR)5, promoted longer and more consolidated sleep in young and old male and female flies.mGluR5 is one of the eight mGluRs, G-protein coupled receptors that modulate synaptic plasticity and neural network activity [18,19].Drosophila has only one mGluR, reflecting the general tendency for low genetic redundancy in flies compared with mammals.Using mGluR mutants, the authors showed that the sleep-promoting effect of DFB required functional mGluR.Consistent with the sleep-promoting effects of DFB, transient pan-neuronal mGluR overexpression improved sleep in young and old flies.Furthermore, the authors found that transcript levels of mGluR and genes encoding its binding partners, homer and shank [20,21], are reduced in aged flies, supporting the view that decreased mGluR activity contributes to age-dependent sleep","journal":"SLEEP","year":2023,"id":403386,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1089847,"name":"Dinis J.S. Afonso","orcid":"0000-0002-7296-0532","position":1,"is_corresponding":false},{"id":339636,"name":"Kyunghee Koh","orcid":"0000-0003-0847-8204","position":2,"is_corresponding":false},{"id":340883,"name":"Sho Inami","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:20:36.280647Z","pmid":"36857139","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}