## 1 Introduction  
Aging is a major risk factor for the onset and progression of neurodegenerative diseases [1]. Even in the absence of pathological conditions, aging is associated with a decline in cognitive functions in both mice and humans [2, 3, 4] ([PERSON], 2012) [5]. Structural alterations in the aging brain include decreases in neuronal spine length and density, reduced memory-related neuronal firing, and changes in glial cell function, including altered astrocyte [6, 7, 8] and microglia function [9, 10]. At the molecular level, shifts in gene expression have been described, reflecting processes such as synaptic transmission, vesicular transport, energy production, and immune activation [2, 3, 11, 12]. However, the mechanisms underlying these changes in gene expression are still not fully understood, particularly concerning glial cells, when compared to neurons.  
The non-coding RNAome has emerged as a critical regulator of gene expression and other cellular functions [13], offering novel and so far unexplored opportunities for therapeutic interventions [14]. Among non-coding RNAs, long non-coding RNAs (lncRNAs) represent a heterogeneous class of RNAs longer than 300 nucleotides that lack coding potential [13; 15]. Key characteristics of lncRNAs, in comparison to protein-coding RNAs, include their relatively lower abundance, preferential nuclear localization, greater tissue- and cell-specific expression patterns, and comparatively lower sequence conservation across species [16]. Due to these features, lncRNAs were long considered transcriptional noise, with research and drug discovery focusing primarily on protein-coding transcripts [17; 18]. However, recent research has highlighted the significant roles of lncRNAs in physiological and pathological conditions, impacting a wide array of biological processes, including genome architecture regulation, gene expression modulation, splicing regulation, and control of protein translation and localization [13]. Additionally, the observation that approximately 40% of human lncRNAs exhibit brain-specific expression patterns suggests that these molecules play complex roles in brain development and function [19], as well as in the pathogenesis of central nervous system disorders [18; 20; 21]. Several studies have demonstrated that lncRNAs are critical in cognitive diseases [22; 23; 24; 25; 26; 27; 28].  
Given the limited research on the role of lncRNAs in the aging brain and the sparse data on non-neuronal glial cells, this study aimed to identify lncRNAs differentially expressed in the hippocampus of aged versus young mice and to investigate the functional implications of candidate lncRNAs. Our findings reveal that one such deregulated lncRNA, _3222401L13 Rik_, which has not been previously studied, is specifically upregulated in astrocytes of aged mice. Antisense oligonucleotide-mediated knockdown of _3222401L13 Rik_ in primary astrocytes, followed by total RNA sequencing, demonstrates its crucial role in regulating genes essential for neuronal support functions. This regulation impacts astrocytic processes such as glutamate uptake and calcium signaling, leading to disruptions in neuronal network plasticity and synapse density. Additionally, we show that its human homolog, _ENSG0000272070_, regulates similar genes and functions in human iPSC-derived astrocytes. Furthermore, we demonstrate that _3222401L13 Rik_ exerts its effects by interacting with and regulating the transcription factor Neuronal PAS Domain Protein 3 (Npas3). Importantly, overexpression of _Npas3_ is sufficient to rescue the functional deficits observed in astrocytes lacking _3222401L13 Rik_.