17-DMAG improves healthspan and stress resistance with trade-offs in lifespan and reproductive capacity in Caenorhabditis elegans Presenting author
10th International Congress of the Molecular Biology Association of Turkey (MolBiyoKon'26)., İstanbul, Türkiye, 17 - 19 Eylül 2026, ss.1-2, (Özet Bildiri)
- Yayın Türü: Bildiri / Özet Bildiri
- Basıldığı Şehir: İstanbul
- Basıldığı Ülke: Türkiye
- Sayfa Sayıları: ss.1-2
- İstanbul Üniversitesi Adresli: Evet
Özet
Background/Aim: Aging is characterized by a progressive decline in proteostasis, stress resistance, and physiological functions, ultimately compromising organismal survival. HSP90 is a molecular chaperone essential for protein homeostasis and cellular stress responses. Its inhibition may activate compensatory stress mechanisms and thus holds considerable potential to modulate lifespan and healthspan. 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) is an HSP90 inhibitor with reported geroprotective and senotherapeutic potential in cellular and animal models. This study investigated the dose-dependent effects of 17-DMAG on lifespan, physiological function, reproduction, and stress resistance in Caenorhabditis elegans (C. elegans).
Materials and Methods: Wild-type N2 C. elegans were treated with vehicle or 10, 15, 20, and 30 µM 17-DMAG from the first day of adulthood. Animals were maintained at 20 °C except during heat-stress exposure. Lifespan, pharyngeal pumping, locomotor activity, survival under acute heat and paraquat-induced oxidative stress, and total viable progeny production were evaluated.
Results: 17-DMAG reduced median lifespan at all tested concentrations. Nevertheless, 10 and 15 µM preserved pharyngeal pumping and locomotor activity during aging and increased survival under heat stress, with the most prominent effects at 15 µM. Only 15 µM improved resistance to paraquat-induced oxidative stress. Higher concentrations were less beneficial, with 20 µM reducing survival under oxidative stress and 30 µM impairing physiological performance and heat-stress resistance. Finally, total viable progeny production decreased following treatment with 15 and 30 µM 17-DMAG.
Conclusion: 17-DMAG did not extend lifespan but exerted dose-dependent effects on healthspan and stress resistance. Moderate concentrations, particularly 10–15 µM, preserved physiological function and enhanced stress resistance, whereas 30 µM was predominantly detrimental. The healthspan benefits observed at 15 µM coincided with reduced progeny production, suggesting a potential trade-off between reproductive investment and somatic maintenance. These findings indicate that HSP90 inhibition may improve specific healthspan parameters independently of lifespan extension, while highlighting the importance of dose and reproductive cost in evaluating the geroprotective potential of 17-DMAG.