The rapid growth of an aging population creates challenges regarding age-related diseases, including AKI, for which both the prevalence and death rate increase with age. The molecular mechanism by which the aged kidney becomes more susceptible to acute injury has not been completely elucidated. In this study, we found that, compared with the kidneys of 3-month-old mice, the kidneys of 20-month-old mice expressed reduced levels of the renal protective molecule sirtuin 1 (SIRT1) and its cofactor NAD Supplementation with nicotinamide mononucleotide (NMN), an NAD precursor, restored renal SIRT1 activity and NAD content in 20-month-old mice and further increased both in 3-month-old mice. Moreover, supplementation with NMN significantly protected mice in both age groups from cisplatin-induced AKI. SIRT1 deficiency blunted the protective effect of NMN, and microarray data revealed that c-Jun N-terminal kinase (JNK) signaling activation associated with renal injury in SIRT1 heterozygotes. , SIRT1 attenuated the stress response by modulating the JNK signaling pathway, probably the deacetylation of a JNK phosphatase, DUSP16. Taken together, our findings reveal SIRT1 as a crucial mediator in the renal aging process. Furthermore, manipulation of SIRT1 activity by NMN seems to be a potential pharmaceutical intervention for AKI that could contribute to the precise treatment of aged patients with AKI.

Epithelial ovarian cancer (EOC) is the sixth most common cancer in females worldwide and, although advances have been made in the detection, diagnosis and therapies for EOC, it remains the most lethal gynecologic malignancy in advanced countries. Nevertheless, relatively little is known concerning the molecular events that lead to the development of this highly aggressive disease. Elucidating the molecular mechanism involved in this disease may prove useful to understand the pathogenesis and progression of the disease, and to identify new targets for effective therapies. In the present study, we examined the role of ARK5 in ovarian cancer and normal matched tissues using western blot analysis and migration and invasion, and wound‑healing assays. The results showed that ARK5 was upregulated in ovarian cancer tissues, compared with adjacent normal tissues. Moreover, it promoted epithelial‑mesenchymal transition (EMT) and inhibited miR-1181 expression in ovarian cancer cells. Subsequent investigations showed that miR-1181 promoted mesenchymal-epithelial transition (MET) in ovarian cancer cells. Downstream target genes of miR-1181 were searched, and it was identified that miR-1181 degraded HOXA10 by targeting its 3' untranslated region (3'UTR) in ovarian cancer cells. The results confirmed that HOXA10 promoted EMT in ovarian cancer cells. Thus, activation of the ARK5/miR-1181/HOXA10 axis may be positively associated with EMT in ovarian cancer.

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