Aging is a complex feature and involves loss of multiple functions and nonreversible phenotypes. However, several studies suggest it is possible to protect against aging and promote rejuvenation. Aging is associated with many factors, such as telomere shortening, DNA damage, mitochondrial dysfunction, and loss of homeostasis. The integrity of the cytoskeleton is associated with several cellular functions, such as migration, proliferation, degeneration, and mitochondrial bioenergy production, and chronic disorders, including neuronal degeneration and premature aging. Cytoskeletal integrity is closely related with several functional activities of cells, such as aging, proliferation, degeneration, and mitochondrial bioenergy production. Therefore, regulation of cytoskeletal integrity may be useful to elicit antiaging effects and to treat degenerative diseases, such as dementia. The actin cytoskeleton is dynamic because its assembly and disassembly change depending on the cellular status. Aged cells exhibit loss of cytoskeletal stability and decline in functional activities linked to longevity. Several studies reported that improvement of cytoskeletal stability can recover functional activities. In particular, microtubule stabilizers can be used to treat dementia. Furthermore, studies of the quality of aged oocytes and embryos revealed a relationship between cytoskeletal integrity and mitochondrial activity. This review summarizes the links of cytoskeletal properties with aging and degenerative diseases and how cytoskeletal integrity can be modulated to elicit antiaging and therapeutic effects.

Ovarian aging is a major obstacle in assisted reproductive medicine because it leads to ovarian dysfunction in women of advanced age. Currently, there are no effective treatments to cure age-related ovarian dysfunction. In this study, we investigated the effect of MIT-001 on the function of aged ovaries. Young and old mice were utilized in this study. MIT-001 was intraperitoneally administered, and the number of follicles and oocytes was analyzed. Each group was then retrieved for RNA and protein isolation. Total RNA was subjected to mRNA next-generation sequencing. Protein extracts from ovarian lysates were used to evaluate various cytokine levels in the ovaries. MIT-001 enhanced follicles and the number of oocytes were compared with non-treated old mice. MIT-001 downregulated immune response-related transcripts and cytokines in the ovaries of old mice. MIT-001 modulates the immune complex responsible for generating inflammatory signals and has the potential to restore the function of old ovaries and improve female fertility.

Poor embryo quality is a major cause of poor clinical outcomes in assisted reproductive medicine, and there are no currently available interventions that can improve embryo quality. Mitochondria dysfunction is linked to low-quality female gametes and zygotes. Previously, microtubule integrity was also associated with mitochondrial function in oocytes. In the present study, we investigated the effects of the microtubule stabilizers (MTS) Taxol and Epothilone D (EpD) and the microtubule disturber (MTD) vinorelbine on mouse preimplantation embryo quality and pregnancy outcome compared with non-treatment controls. We prepared young BDF1 mice (7~9 weeks old) and cultured preimplantation embryos with MTS or MTD. Mitochondrial functional activity and embryo development ratios including pregnancy ratios were then assessed. MTS-treated embryos showed significantly increased mitochondrial membrane potentials and motility. Blastocyst formation was significantly higher in MTS-treated embryos than in MTD-treated embryos. Especially, MTS-treated embryos exhibited higher hatched blastocyte formation than untreated embryos. The number of offspring was significantly higher in surrogate mice transplanted with MTS-treated embryos. These findings demonstrated that the treatment of mouse preimplantation embryos with Taxol or EpD increased embryo development competence, which was associated with increased mitochondrial functional activity. Consistently, delivery ratios were significantly higher after transplantation with MTS-treated embryos than after transplantation with untreated embryos. These findings suggest that MTS could be used to supplement in vitro culture media to promote the recovery of poor-quality embryos.

Poor embryo quality is a major cause of poor clinical outcomes in assisted reproductive medicine, and there are no currently available interventions that can improve embryo quality. Mitochondria dysfunction is linked to low-quality female gametes and zygotes. Previously, microtubule integrity was also associated with mitochondrial function in oocytes. In the present study, we investigated the effects of the microtubule stabilizers (MTS) Taxol and Epothilone D and the microtubule disturber (MTD) vinorelbine on mouse preimplantation embryo quality and pregnancy outcome. We prepared young BDF1 mice (7~9 weeks old) and cultured preimplantation embryos with MTS or MTD. Mitochondrial functional activity and embryo development ratios including pregnancy ratios were then assessed. MTS-treated embryos showed significantly increased mitochondrial membrane potentials and motility. Blastocyst formation was significantly higher in MTS-treated embryos than in MTD-treated embryos. Especially, MTS-treated embryos exhibited higher hatched blastocyte formation than untreated embryos. The number of offspring was significantly higher in surrogate mice transplanted with MTS-treated embryos. These findings demonstrated that treatment of mouse preimplantation embryos with Taxol or EpD increased embryo development competence, which was associated with increased mitochondrial functional activity. Consistently, delivery ratios were significantly higher after transplantation with MTS-treated embryos than after transplantation with untreated embryos. These findings suggest that MTS could be used to supplement in vitro culture media to promote the recovery of poor-quality embryos.