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Mitochondrial Imbalance in Down Syndrome: A Driver of Accelerated Brain Aging?
Zuo X.. Aging and disease, 2025-04-06
Topic: Brain proteins, microglia and lab models
Down syndrome (DS), caused by trisomy of chromosome 21 (HSA21), is a complex condition associated with neurodevelopmental impairments and accelerated brain aging, often culminating in early-onset Alzheimer's disease (AD). Central to this accelerated aging is mitochondrial imbalance, characterized by disrupted energy metabolism, increased oxidative stress, impaired dynamics, and defective quality control mechanisms like mitophagy. These abnormalities exacerbate neuronal vulnerability, driving cognitive decline and neurodegeneration. This review examines the genetic and biochemical underpinnings of mitochondrial dysfunction in DS, with a focus on the role of HSA21-encoded genes. We also highlight how mitochondrial dysfunction, amplified by oxidative stress and HSA21 gene dosage effects, converges with cellular senescence and neuroinflammation to accelerate Alzheimer-like pathology and brain aging in DS. Finally, we discuss emerging therapeutic strategies targeting mitochondrial pathways, which hold promise for mitigating neurodegenerative phenotypes and improving outcomes in DS.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zuo, X. (2025). Mitochondrial Imbalance in Down Syndrome: A Driver of Accelerated Brain Aging? Aging and disease. https://doi.org/10.14336/ad.2025.0189
Vancouver
Zuo X. Mitochondrial Imbalance in Down Syndrome: A Driver of Accelerated Brain Aging? Aging and disease. 2025. doi:10.14336/ad.2025.0189. PMID: 40249934.
BibTeX
@article{zuo2025-40249934,
author = {Zuo, X.},
title = {{Mitochondrial Imbalance in Down Syndrome: A Driver of Accelerated Brain Aging?}},
journal = {Aging and disease},
year = {2025},
doi = {10.14336/ad.2025.0189},
pmid = {40249934},
url = {https://doi.org/10.14336/ad.2025.0189}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Down syndrome (DS), caused by trisomy of chromosome 21 (HSA21), is a complex condition associated with neurodevelopmental impairments and accelerated brain aging, often culminating in early-onset Alzheimer's disease (AD).
Why it matters
This review describes how mitochondrial imbalance in Down syndrome, driven partly by genes on chromosome 21, is thought to contribute to accelerated brain aging and Alzheimer-like pathology. It discusses emerging therapies targeting mitochondrial pathways but reports no tested treatment or outcome in patients.
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 senior author's track record, so that was left out: it earned 35 of the 96 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Aging and disease) |
| Journal's citation record | 1 / 4 | Aging and Disease: journal h-index 107 (OpenAlex, 2026-10-29) |
| 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 | 4 / 5 | 2025 — within 3 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 | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Xinxin Zuo holds only 7 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40249934) |
| Free to read | 2 / 2 | Free to read |
| Points | 35 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 35 of the 96 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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