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SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1β
Seo-Hyun Cho, Jason A. Chen, Faten Sayed, Michael E. Ward, Fuying Gao, Thi A. Nguyen, Grietje Krabbe, Peter Dongmin Sohn et al.. The Journal of Neuroscience, 2015-01-14
Topic: Inflammation, microglia and astrocytes
Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as the brain ages is an aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we report a mechanistic link between chronic inflammation and aging microglia and a causal role of aging microglia in neurodegenerative cognitive deficits. We showed that SIRT1 is reduced with the aging of microglia and that microglial SIRT1 deficiency has a causative role in aging- or tau-mediated memory deficits via IL-1β upregulation in mice. Interestingly, the selective activation of IL-1β transcription by SIRT1 deficiency is likely mediated through hypomethylating the specific CpG sites on IL-1β proximal promoter. In humans, hypomethylation of IL-1β is strongly associated with chronological age and with elevated IL-1β transcription. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in aging and neurodegenerative diseases.
Key findings
- We showed that SIRT1 is reduced with the aging of microglia and that microglial SIRT1 deficiency has a causative role in aging- or tau-mediated memory deficits via IL-1β upregulation in mice.
- In humans, hypomethylation of IL-1β is strongly associated with chronological age and with elevated IL-1β transcription.
- Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in aging and neurodegenerative diseases.
Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 20 of the 56 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of Neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 20 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 20 of the 56 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Cho, S.-H., Chen, J. A., Sayed, F., Ward, M. E., Gao, F., Nguyen, T. A., et al. (2015). SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1β. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.2939-14.2015
Vancouver
Cho S.-H, Chen JA, Sayed F, Ward ME, Gao F, Nguyen TA, et al. SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1β. The Journal of Neuroscience. 2015. doi:10.1523/jneurosci.2939-14.2015.
BibTeX
@article{cho2015-e082a2d8,
author = {Cho, Seo-Hyun and Chen, Jason A. and Sayed, Faten and Ward, Michael E. and Gao, Fuying and Nguyen, Thi A. and Krabbe, Grietje and Sohn, Peter Dongmin and others},
title = {{SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1β}},
journal = {The Journal of Neuroscience},
year = {2015},
doi = {10.1523/jneurosci.2939-14.2015},
url = {https://doi.org/10.1523/jneurosci.2939-14.2015}
}