The Clearance Effect of Tetrahedral DNA Nanostructures on Senescent Human Dermal Fibroblasts
Chenchen Mao1, Weiyi Pan1, Xiaoru Shao1
1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology , Sichuan University , Chengdu , China.
Abstract:
Senescent cells are characterized by their resistance to apoptosis, and upon their long-term survival senescent cells affect tissue function and eventually become deleterious to the organism. Thus, far, it has been gradually accepted that clearance of these senescent cells could reduce tissue dysfunction. This study aimed to investigate biological effects of tetrahedral DNA nanostructures (TDNs) on senescent cells. The results revealed a different biological effect of TDNs, and their clearance effect on senescent cells. TDNs can induce phenotypic changes in senescent cells, suppressing antiapoptotic BCL-2 family proteins and upregulating BAX, a BCL-2 family proapoptotic protein, to influence the expression levels and function of downstream proteins. Consequently, cytochrome C releasing promoted cleavage-mediated activation of pro-caspase-3 and its nuclear translocation from the cytoplasm to mediate apoptosis. The present results provide a foundation for further studies on the application of TDNs in studies on aging.
Insights
Tetrahedral DNA nanostructures (TDNs) can clear senescent cells by inducing apoptosis. This study shows TDNs suppress antiapoptotic proteins and activate proapoptotic pathways, offering a new approach for aging research.
Area of Science:
- Biotechnology
- Cell Biology
- Molecular Biology
Background:
- Senescent cells resist apoptosis and negatively impact tissue function and organismal health.
- Clearance of senescent cells is a promising strategy to mitigate age-related tissue dysfunction.
Purpose of the Study:
- To investigate the biological effects of tetrahedral DNA nanostructures (TDNs) on senescent cells.
- To explore the potential of TDNs for clearing senescent cells.
Main Methods:
- Treatment of senescent cells with TDNs.
- Analysis of protein expression levels, focusing on BCL-2 family members (antiapoptotic and proapoptotic).
- Assessment of apoptosis-related signaling pathways, including caspase-3 activation and cytochrome C release.
Main Results:
- TDNs induced phenotypic changes in senescent cells.
- TDNs suppressed antiapoptotic BCL-2 family proteins and upregulated the proapoptotic BAX protein.
- TDNs promoted cytochrome C release, leading to caspase-3 activation and apoptosis.
Conclusions:
- TDNs effectively induce apoptosis in senescent cells.
- TDNs demonstrate a senolytic effect by targeting key apoptotic pathways.
- These findings establish a basis for applying TDNs in aging and senescence research.
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