## 3 Discussion
These data strongly suggest that _3222401L13 Rik_ orchestrates the regulation of astroglia function--at least in part--via Npas3. Taking into account that _3222401L13 Rik_ expression increases in the aging brain and that its knockdown impairs astrocytes' ability to perform critical neuronal support functions, it can be speculated that altered _3222401L13 Rik_ expression may represent an adaptive mechanism aimed at mitigating ongoing network imbalances and functional alterations associated with aging. This would further imply that increasing _3222401L13 Rik_ expression or strengthening the interaction of _3222401L13 Rik_ and Npas3 in early aging processes or at the onset of neurodegenerative diseases such as AD could be a potential clinical option to delay the onset of neuronal dysfunction. However, further studies are needed to determine whether modulating _3222401L13 Rik_ and _ENSG00000272070_ levels can indeed enhance astrocytic function and neuronal support during aging and neurodegeneration. To this end, preclinical studies using animal models or human iPSC cellular systems that mimic neuronal dysfunction or neurodegeneration should explore approaches to increase _3222401L13 Rik_ expression in astrocytes, such as CRISPR-based methods. Our study has several limitations that should be acknowledged. First, increasing evidence reveals distinct astrocyte subtypes within and between brain regions [57]. Since our study focused on the hippocampus, it would be important to investigate the role of _3222401L13 Rik_ and _ENSG00000272070_ in other brain regions. Additionally, analyzing the expression of these lncRNAs in postmortem human brains from both young and old individuals, as well as those with cognitive diseases, would be crucial. Ideally, this should be complemented by similar analyses in animal models, allowing us to determine if _3222401L13 Rik_ expression is a compensatory mechanism aimed at ameliorating the detrimental effects of brain aging. This is particularly interesting given recent data suggesting a key role of astrocytes in mediating resilience to cognitive decline [44]. It would also be valuable to study the functional role of _3222401L13 Rik_ in an in vivo system. The knockdown of _3222401L13 Rik_ in wild-type mice and its overexpression in disease models could provide important insights critical for the preclinical development of RNA-based cognitive enhancers. However, preclinical research involving mice is becoming increasingly difficult in the European Union, particularly in Germany, and we are unable to perform such experiments within a reasonable time frame. Finally, our dataset suggests several other lncRNAs that are deregulated in the aging mouse brain and have human homologs. In addition to _Neat1_, which is well-studied for its role in brain function and disease [25; 58; 59; 60; 61], we identified _A330023F24 Rik, Lucpint, Gm12689, Mir124-2 lbg, B130024G19 Rik, C430049B03 Rik_, and _Gm45847_ as being deregulated in the aging mouse hippocampus and having human homologs. _A330023F24 Rik_ is deregulated in Duchenne muscular dystrophy [62] and in response to optic nerve injury [63]. _Lucpint_, a neuron-enriched lncRNA, is increased in various neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease, and Huntington's disease, and functional studies suggest a protective role since the loss of Lncpint exacerbates pathology [64], which is similar to our data on _3222401L13 Rik_. _Mir124-2 lbg_ is also a neuron-enriched lncRNA with a reported role in synaptic vesicle recycling [65] that warrants further analysis in neurons. The human homolog of _B130024G19 Rik_, _NR2F2-AS1_, has been studied in various cancers, as has _C430049B03 Rik_ and its human homolog _MIR503 HG_. In summary, our study identifies the novel lncRNA _3222401L13 Rik_ as crucial in regulating astrocytic gene expression through its interaction with the transcription factor Npas3.