Date of Award:

8-2026

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Veterinary Clinical and Life Science Department

Committee Chair(s)

Mirella Meyer-Ficca

Committee

Mirella Meyer-Ficca

Committee

Ralph G. Meyer

Committee

Aaron Thomas

Committee

Rakesh Kaundal

Committee

Cathleen Kovarik

Abstract

Nicotinamide adenine dinucleotide (NAD) is a molecule that plays essential roles in energy production, metabolism, and cellular signaling, including processes such as DNA repair and regulation of gene activity. NAD levels decrease with age, but it is not clear whether this decline contributes to aging or reflects other biological changes that occur with age. This dissertation examines how reduced NAD levels influence biological processes across tissues and compares these effects to natural aging. Using a mouse model in which NAD levels can be lowered through diet, this work directly compares NAD deficiency with aging across multiple tissues, including the liver, kidney, muscle, and testis. To understand these effects, multiple types of molecular data were collected, including gene expression, metabolic profiles, and epigenetic markers. These approaches allowed detailed analysis of how cells and tissues respond to NAD deficiency and aging. The results show that NAD deficiency and aging can produce similar changes in some tissues but differ in others. In the liver, kidney, and muscle, there was significant overlap between the effects of NAD deficiency and aging, although each condition also produced unique changes. In contrast, in the testis, NAD deficiency and aging had largely distinct effects, including differences in the cells involved in sperm production and in the signals that regulate this process. Overall, this work clarifies how declining NAD levels relate to aging and provides insight into how metabolism influences health across tissues. These findings may help guide future efforts to target NAD metabolism in aging and disease.

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