Combining adoptive NK cell infusion with a dopamine-releasing peptide reduces senescent cells in aged mice
Open accessAbstract
Aging inducing the development of senescent cells (SNCs) in various tissues is considered as the main cause of the age-related diseases. Senotherapy has become a promising anti-aging therapy. However, the effectivity and side-effect of senolytic agents are still concern. Here, we observed the downregulation of senescence-related genes by adoptive infusion of natural killer (NK) cells in 26 cases in peripheral blood CD3 + T cells. NK cell treatment also significantly decreased levels of senescence markers and senescence-associated secretory phenotypes (SASPs) in three senescent adipose tissues when culturing them together. Interestingly, cytotoxic activity of mouse NK cells against SNCs was significantly enhanced by dopamine in vitro through D1-like receptors. Acein, dopamine-releasing peptide, promoted the adoptive infusion of NK cells in effectively eliminating SNCs in a variety of tissues and reduced local and systemic SASPs in aging mice but Acein alone did not have the senolytic effect. These data demonstrated that adoptive infusion of NK cells is an effective means in removing SNCs, and peptide Acein combined with NK cells further enhances this effect in aging mice.
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In aged mice and healthy/obese volunteers, adoptive NK cell infusion significantly reduced senescence markers and SASP levels without significant toxic side effects.
“In the aged mice and healthy/obese volunteers, adoptive NK cell infusion significantly reduced senescence markers and SASP levels without significant toxic side effects.353,354”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [353]
The Results (pages not provided) report reduced senescence markers and SASP factors after NK-cell infusion in aged mice, and reduced senescence markers and Pai1 in peripheral-blood T cells from 26 volunteers; IL-6 and MCP-1 did not change significantly. Adipose tissue from obese individuals was treated with NK cells outside the body, not by infusion into those individuals. The volunteers’ biochemical indexes did not change significantly, but that alone does not establish an absence of significant toxic side effects. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCombination of NK cells with the immunomodulatory factor Acein significantly decreased the expression of tissue senescence markers and age-related genes in a mouse model of senescence.
“In addition, their combination with the immunomodulatory factor Acein significantly decreased the expression of tissue senescence markers and age-related genes in a mouse model of senescence.353”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [353]
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Inflammation and aging: signaling pathways and intervention therapies
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ResultOverview of Innate Immune Cell Landscape in Liver Aging
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“More definitively, NK cell adoptive transfer has demonstrated efficacy in rejuvenating immu-nosenescent systems, clearing senescent cells (SNCs) from tissues, and reducing SASP factors—highlighting its therapeutic potential for age-related pathologies [68–70].”
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“Cellular and hepatic tissue cAMP assay Cellular cAMP assay was performed as previously described [19].”
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Photoactivatable Exosenolytics Activate Natural Killer Cells for Delaying Osteoarthritis
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- Authors
- Bai, Z., Yang, P., Yu, F., Li, Z., Yao, Z., Martinez, J., Li, M., & Xu, H.
- Affiliations
- China Pharmaceutical University (CN)
- Shanghai Cell Therapy Research Institute (CN)
- Corresponding author
- Xu, Hanmei
- Venue
- Cell Death & Disease
- Published
- 2022-04-05
- Volume
- 13
- Issue
- 4
- Pages
- 305-305
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC8983684
- OpenAlex
- W4224315791
- Cited by
- 43
- References
- 45
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 9 · 2023: 8 · 2022: 1
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province (SKLNMKF202008, BK20180569)
- State Key Laboratory of Natural Medicines (SKLNMKF202008, SKLNMZZCX201821)
- Priority Academic Program Development of Jiangsu Higher Education Institutions (CPU2018GY13)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Keywords
- senolytic therapy, senescent cells, natural killer cells, senescence-associated secretory phenotype, D1-like receptors, aging, adipose tissue, age-related diseases, cytotoxicity
- MeSH terms
- Aging, Animals, Dopamine, Killer Cells, Natural, Peptides, Cellular Senescence, Mice
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