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Senescence in Aging and Alzheimer's Disease
Li Sun, Chu Chen. Aging and disease, 2025-11-25
Topic: Disease mechanisms in lab and animal studies
Cellular senescence, once considered a protective mechanism against oncogenesis, is now recognized as a key driver of aging and age-related diseases, including Alzheimer's disease (AD). In the central nervous system (CNS), senescence-like states emerge in both proliferative and post-mitotic cells-astrocytes, microglia, oligodendrocyte lineage cells, endothelial cells, pericytes, and even neurons-contributing to chronic dysfunction. Canonical pathways, such as p16INK4a-pRB and p53-p21, enforced by persistent DNA damage responses, lead to irreversible cell-cycle arrest. The senescence-associated secretory phenotype (SASP) links intracellular stress to extracellular inflammation, tissue remodeling, and bystander senescence. CNS senescence is triggered by diverse insults, including amyloid-β and tau pathology, oxidative stress, mitochondrial dysfunction, NF-κB and cGAS-STING signaling, impaired proteostasis and autophagy, telomere attrition, and genomic instability. Senescence markers in the CNS are heterogeneous, ranging from p16/p21 expression and lamin B1 loss to lipofuscin accumulation and cell type-specific SASP profiles, highlighting the need for multiplexed detection strategies. Targeting senescence has emerged as a promising therapeutic avenue in AD. Senolytics selectively eliminate senescent cells and improve cognition in preclinical models, while senomorphics aim to suppress harmful phenotypes without inducing cell loss. Early clinical trials suggest feasibility, but challenges remain, including biomarker development, blood-brain barrier penetration, long-term safety, and optimal timing of intervention. This review summarizes recent advances in understanding CNS senescence in aging and AD, explores emerging therapeutic strategies, and outlines future directions emphasizing precision medicine through multi-omic biomarkers, advanced imaging, and stage-specific interventions. Targeting CNS senescence holds potential to delay or alter the course of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Sun, L., & Chen, C. (2025). Senescence in Aging and Alzheimer's Disease. Aging and disease. https://doi.org/10.14336/ad.2025.1201
Vancouver
Sun L, Chen C. Senescence in Aging and Alzheimer's Disease. Aging and disease. 2025. doi:10.14336/ad.2025.1201. PMID: 41296937.
BibTeX
@article{sun2025-41296937,
author = {Sun, Li and Chen, Chu},
title = {{Senescence in Aging and Alzheimer's Disease}},
journal = {Aging and disease},
year = {2025},
doi = {10.14336/ad.2025.1201},
pmid = {41296937},
url = {https://doi.org/10.14336/ad.2025.1201}
}
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Key findings
- Targeting senescence has emerged as a promising therapeutic avenue in AD.
- Senolytics selectively eliminate senescent cells and improve cognition in preclinical models, while senomorphics aim to suppress harmful phenotypes without inducing cell loss.
- Early clinical trials suggest feasibility, but challenges remain, including biomarker development, blood-brain barrier penetration, long-term safety, and optimal timing of intervention.
- This review summarizes recent advances in understanding CNS senescence in aging and AD, explores emerging therapeutic strategies, and outlines future directions emphasizing precision medicine through multi-omic biomarkers, advanced imaging, and stage-specific interventions.
- Targeting CNS senescence holds potential to delay or alter the course of AD.
Study details
- Evidence strengthLow
How this study scored 43/100
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 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Aging and disease) |
| 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 | 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 | — / 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 | 2 / 2 | Indexed in PubMed (PMID 41296937) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
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