Nicotinamide Supplementation Improves Oocyte Quality and Offspring Development by Modulating Mitochondrial Function in an Aged Caenorhabditis elegans Model

Abstract

Aging is associated with a decline in the quality of biological functions. Among the aging processes, reproductive aging is a critical process because of its intergenerational effects. However, the mechanisms underlying reproductive aging remain largely unknown. Female reproductive aging is the primary reason for limited fertility in mammals. Therefore, we attempted to investigate a modulator that can control female reproductive aging using a Caenorhabditis elegans model. In the present study, we examined the role of nicotinamide (NAM) in oocyte quality and offspring development. The levels of reactive oxygen species (ROS) and oxidative stress responses in aged oocytes, embryonic lethality, and developmental growth of the offspring were examined with maternal NAM supplementation. Supplementation with NAM improved oocyte quality, decreased embryonic lethality, and promoted germ cell apoptosis. Furthermore, NAM supplementation in aged mothers reduced ROS accumulation and improved mitochondrial function in oocytes. Consequently, the developmental growth and motility of offspring were improved. These findings suggest that NAM supplementation improves the health of the offspring produced by aged mothers through improved mitochondrial function. Taken together, our results imply that NAM supplementation in the aged mother improves oocyte quality and protects offspring by modulating mitochondrial function.

Long-Term Caffeine Intake Exerts Protective Effects on Intestinal Aging by Regulating Vitellogenesis and Mitochondrial Function in an Aged Caenorhabditis Elegans Model

“…It has been suggested that immunity and antioxidant defense, which regulate ROS production in response to bacterial colonization during intestinal aging, are major effectors of aging and lifespan in C. elegans [ 43 , 44 ]. Given that caffeine intake suppresses bacterial colonization of the intestine in aging animals ( Figure 1 D), we measured mitochondrial ROS levels using CellROX Green, which is a fluorogenic probe for measuring mitochondrial ROS in live cells [ 38 ]. We observed that the fluorescence intensity decreased significantly in the long-term caffeine-ingested wild-type animals ( Figure 3 A).…”

“…To examine the effect of caffeine intake on the mitochondrial ROS, CellROX ® Green (Invitrogen, Carlsbad, CA, USA) staining was performed as described previously [ 4 , 38 ]. Briefly, CellROX ® Green was freshly prepared as 5 mM stock solutions and diluted in the M9 buffer at a 1:500 dilution before treatment.…”

“…To measure MMP, tetramethylrhodamine methyl ester (TMRM; Thermo Fisher Scientific, Waltham, MA, USA) staining was performed as previously described [ 38 ]. Briefly, TMRM (final concentration: 30 µM) was added to NGM agar plates containing 0 or 10 mM caffeine.…”

“…To analyze the effect of long-term caffeine intake on motility, body bends were measured as previously described [ 38 ]. Briefly, animals from each test condition were transferred onto separate NGM plates and scored for the number of body bends at 20 s intervals.…”

“…The paraquat survival assay was performed as previously described, with minor modifications [ 38 ]. To analyze the survival rates under oxidative stress conditions in each group, the synchronized 72 h post-L4-stage animals were exposed to 100 mM paraquat solution at 20 °C for 3 h, and subsequently, the number of dead and live animals were counted.…”