Despite the increasing numbers of aging individuals in our country, there is little understanding of theinteraction between the mechanisms of aging and the pathophysiology of age-related diseases. Research inthis area is essential since age is the largest risk factor for various diseases. If this relationship can be resolved,it would open new avenues for therapeutic interventions to treat/prevent age-related diseases. Oxidative stressis one of the fundamental biological processes that link aging and age-related diseases.

Aging is the strongest known risk factor for Alzheimer's disease (AD), the most common cause ofdementia in older individuals. However, effective AD therapies remain elusive, which underscores the need tobetter understand disease etiology and its co-occurrence with advanced age. Apolipoprotein E (apoE) is amajor lipid carrier in the brain that transports cholesterol and other lipids such as sulfatide (a key component ofmyelin) between brain cells. APOE polymorphic alleles are the main genetic determinants of AD risk (e.g.,APOE4 allele is the strongest genetic risk factor for AD).

Oral health is associated with nutritional intake and overall well-being in elderly populations and progressivelydeteriorates with aging. In addition, salivary gland function, which plays a major role in oral defense, alsodecreases with age. However, the mechanisms involved in this age-related decline have not beencomprehensively studied due to a lack of proper laboratory animal models for studying changes in oral healthwith aging. The common marmoset is a relatively short-lived non-human primate (NHP) that recapitulates manyof the physiological changes that occur in human aging.

Emerging evidence supports the proposition that the mitochondrial respiratory chain (MRC) functions viaorganized multicomplex structures called supercomplexes. However the dynamics and regulation ofsupercomplex assembly have not been fully investigated. In particular, hardly any regulatory protein factorsinvolved in supercomplex assembly have been identified. Our long term goal is to understand the dynamics ofmitochondrial respiratory machinery and its underling regulatory mechanism.

Alzheimer's disease (AD) affects 5.5 million Americans producing cognitive deficits and mortality. Thereis no treatment for AD, thus, development of interventions to slow or reverse AD symptoms is a critical area ofresearch. Furthermore, AD is difficult to detect until substantial neurodegeneration has already occurred. Thisproposal investigates proteasome function both as an intervention to AD symptoms and as a tool for earlystage diagnosis in peripheral tissues. A key symptom of AD is proteostatic dysfunction.

Over 47% of family members who care for a relative with Alzheimer?s disease or a related dementia (ADRD) engage in physical or psychological abuse or neglect. Cross-sectional studies report caregiver stress and behavioral symptoms of dementia are correlated with elder abuse and neglect (EAN), making the caregiver burden theory the leading explanation for EAN.