Importance of Mitochondrial NADPH Generating Enzymes for Longevity

Authors' Affiliations

Henry Gong, Patrick Bradshaw Department of Biomedical Science, Quillen College of Medicine.

Location

WhiteTop Mountain Room 225

Start Date

4-5-2018 8:00 AM

End Date

4-5-2018 12:00 PM

Poster Number

109

Name of Project's Faculty Sponsor

Patrick Bradshaw

Faculty Sponsor's Department

Biomedical Science

Classification of First Author

Graduate Student-Doctoral

Type

Poster: Competitive

Project's Category

Biomedical and Health Sciences

Abstract or Artist's Statement

Reactive oxygen species (ROS), and the resulting oxidative stress caused by these species, have long been attributed to be one of the causes for aging and age related disorders. NADPH, the reduced form of nicotinamide adenine dinucleotide phosphate (NADP), provides a critical and essential buffer against cellular toxicity due to ROS. NADPH is one of the cells most powerful reducing agents, capable of regenerating other endogenous antioxidants such as glutathione from its oxidized form, glutathione disulfide. Consequently, it is hypothesized that declining NADPH levels with age results in a depletion in cellular capacity to respond to ROS induced damage, further accelerating the aging process. To study the importance of NADPH on the aging process as well as the molecular mechanisms involved, lifespan assays were performed using knockdown of various enzymes involved in the production of NADPH in Caenorhabditis elegans. Preliminary results indicate declining NADPH levels do have an effect on expected longevity. More interesting however, is a possibly important distinction between cytoplasmic and mitochondrial enzymes involved in the production of NADPH. These preliminary results suggest the existence of a previously undescribed molecular mechanism that is potentially important to the aging process. However, further experiments and analysis are required to further elucidate these mechanisms and to confirm preliminary findings.

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Apr 5th, 8:00 AM Apr 5th, 12:00 PM

Importance of Mitochondrial NADPH Generating Enzymes for Longevity

WhiteTop Mountain Room 225

Reactive oxygen species (ROS), and the resulting oxidative stress caused by these species, have long been attributed to be one of the causes for aging and age related disorders. NADPH, the reduced form of nicotinamide adenine dinucleotide phosphate (NADP), provides a critical and essential buffer against cellular toxicity due to ROS. NADPH is one of the cells most powerful reducing agents, capable of regenerating other endogenous antioxidants such as glutathione from its oxidized form, glutathione disulfide. Consequently, it is hypothesized that declining NADPH levels with age results in a depletion in cellular capacity to respond to ROS induced damage, further accelerating the aging process. To study the importance of NADPH on the aging process as well as the molecular mechanisms involved, lifespan assays were performed using knockdown of various enzymes involved in the production of NADPH in Caenorhabditis elegans. Preliminary results indicate declining NADPH levels do have an effect on expected longevity. More interesting however, is a possibly important distinction between cytoplasmic and mitochondrial enzymes involved in the production of NADPH. These preliminary results suggest the existence of a previously undescribed molecular mechanism that is potentially important to the aging process. However, further experiments and analysis are required to further elucidate these mechanisms and to confirm preliminary findings.