KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER | 
|---|---|---|
| Antibodies | ||
| anti-TERT | Abcam | Cat#: ab32020  RRID: AB_778296  | 
| anti-H3K9me3 | Abcam | Cat#: ab8898  RRID: AB_306848  | 
| anti-H3K27ac | Abcam | Cat#: ab4729  RRID: AB_2118291  | 
| anti-pERK | Cell Signaling Tech | Cat#: 9101  RRID: AB_331646  | 
| anti-ERK | Cell Signaling Tech | Cat#: 4695  RRID: AB_390779  | 
| anti-FOS | Cell Signaling Tech | Cat#: 2250  RRID: AB_2247211  | 
| anti-p16 | Abcam | Cat#: ab211542  RRID: AB_2891084  | 
| anti-DCX | Abcam | Cat#: ab18723  RRID: AB_732011  | 
| anti-DCX | Santa Cruz Biotech | Cat#: sc-271390  RRID: AB_10610966  | 
| anti-PSA-NCAM | EMD Millipore | Cat#: MAB5324  RRID: AB_95211  | 
| anti-IBA1 | Wako | Cat#: 019-19741  RRID: AB_839504  | 
| anti-IL-1β | Cell Signaling Tech | Cat#: 12242  RRID: AB_2715503  | 
| anti-IL-6 | Protein Tech | Cat#: 21865-1-AP  RRID: AB_11142677  | 
| anti-Tubulin | Sigma | Cat#: T5168  RRID: AB_477579  | 
| Chemicals, Peptides, and Recombinant Proteins | ||
| Dulbecco's phosphate-buffered saline | GIBCO | 14190144 | 
| Hanks' balanced salt solution | GIBCO | 14170112 | 
| poly-D-lysine | Sigma | P6407 | 
| poly-L-ornithine | EMD Millipore | A-004-C | 
| Laminin | Sigma | L2020 | 
| Eagle’s MEM | ATCC | 30-2003 | 
| Fetal Bovine Serum | GIBCO | 10082147 | 
| Penicillin/Streptomycin | GIBCO | 15140122 | 
| Neurobasal medium | GIBCO | 12348-017 | 
| B-27 Supplement | GIBCO | 35050-061 | 
| N-2 Supplement | GIBCO | 17502-048 | 
| GlutaMAX Supplement | GIBCO | 35050-061 | 
| MEM Non-Essential Amino Acids | GIBCO | 11140-050 | 
| DMEM/F12 | GIBCO | 11330-032 | 
| Human BDNF | Peprotech | 450-02 | 
| Human GDNF | Peprotech | 450-10 | 
| Dibutyryl cyclic AMP | Sigma | D0627 | 
| L-Ascorbic acid | Sigma | A4544 | 
| NSC maintenance media | EMD Millipore | SCM005 | 
| Recombinant human FGF-basic | Peprotech | AF-100-18B | 
| ChIP-Grade Protein A/G Plus Agarose | Thermo Scientific | 26159 | 
| Halt protease and phosphatase inhibitor cocktail | Thermo Scientific | 78442 | 
| X-tremeGENE HP DNA Transfection reagent | Millipore Sigma | 6366236001 | 
| Ficoll-Paque premium | Sigma | GE17-5446-02 | 
| TRIzol Reagent | Invitrogen | 15596026 | 
| SuperScript III First-Strand Synthesis System | Invitrogen | 18080-051 | 
| SYBR Green PCR Master Mix | Invitrogen | 4309155 | 
| Trametinib | Selleck Chemicals | S2673 | 
| T-5224 | Selleck Chemicals | S8966 | 
| Critical Commercial Assays | ||
| EZ DNA Methylation-Gold™ kit | Zymo Research | ZD5005 | 
| Human phospho-kinase array kit | R&D Systems | ARY003B | 
| Dual-luciferase reporter assay system | Promega | E1910 | 
| Senescence β-Galactosidase staining kit | Cell Signaling Tech | 9860 | 
| Mature BDNF mouse rapid ELISA assay | Biosensis | BEK-2211 | 
| Protein synthesis assay kit | Cayman Chemical | 601100 | 
| Deposited Data | ||
| RNA-seq data of WT and Tert−/− mouse brains | Shim et al., 2021 | GSE163524 | 
| RNA-seq and ChIP-seq data | This paper | 
GSE231454,  GSE231455  | 
| Experimental Models: Cell Lines | ||
| Mouse: Primary ear fibroblasts from hTERT-Rluc transgenic mouse | Jia et al., 2011 | N/A | 
| Mouse: Primary cardiomyocytes | This paper | N/A | 
| Mouse: Primary microglia cells | This paper | N/A | 
| Mouse: Primary neuronal cells | This paper | N/A | 
| Human: MRC-5 fibroblasts | ATCC | Cat#: CCL-171 | 
| Human: Werner syndrome (WS) fibroblasts | Coriell Institute | Cat#: AG03141 | 
| Human: NPCs derived from NDC's iPSCs | Raja et al., 2016 | N/A | 
| Experimental Models: Organisms/Strains | ||
| C57BL/6 | The Jackson Laboratory | JAX: 000664 | 
| LSL-mTERT (B6 background) | Chakravarti et al., 2020 | N/A | 
| hTERT-Rluc transgenic mouse | Jia et al., 2011 | N/A | 
| Recombinant DNA | ||
| pGL4-hTERT-promoter-4kb-WT | This study | N/A | 
| pGL4-hTERT-promoter-4kb-ΔAP1-#1 | This study | N/A | 
| pGL4-hTERT-promoter-4kb-ΔAP1-#2 | This study | N/A | 
| pGL4-hTERT-promoter-4kb-ΔAP1-#1 | This study | N/A | 
| Software and Algorithms | ||
| ImageJ v1.53a | NIH | |
| GraphPad Prism v8 | GraphPad Software | |
| htseq-count package | Anders et al., 2015 | |
| DESeq2 package | Love et al., 2014 | |
| Bowtie v1.2.2 | Langmead et al., 2009 | |
| SAMtools v1.9 | Li et al., 2009 | |
| MACS v1.4.2 | Zhang et al., 2008 | |
| GSEA v4.1.0 | Broad Institute | |
| BioRender | BioRender | |
| Other | ||
| Barnes Maze apparatus (basic mouse) | Panlab Harvard Apparatus | Cat#: 989999 | 
| Y-maze apparatus (with door, mouse) | Panlab Harvard Apparatus | Cat#: 760079 | 
| Rotarod (mouse) | Panlab Harvard Apparatus | Cat#: 760770 | 
| Grip strength meter (mouse) | Panlab Harvard Apparatus | Cat#: 761068 | 
| Bioruptor Pico sonication system | Diagenode | |
| HiSeq 4000 | Illumina |