Thesis--Wisconsin. / Vita. Includes bibliographical references (leaves 98-104).

Thesis--Wisconsin. / Includes bibliographical references (leaves [41]-46).

BACKGROUND: Low testosterone levels in older women have been shown to be associated with frailty. Whether older postmenopausal women with a history of bilateral oophorectomy before natural menopause resulting in lower testosterone levels (surgical menopause) have higher risk for frailty is not known. This prospective study investigated whether women who had surgically-induced menopause had a greater risk of frailty than naturally menopausal women. Furthermore, we also determined whether lower serum testosterone levels would be associated with frailty in our study population of older postmenopausal women. METHODS: The sample included 7699 community-dwelling white women aged ≥ 65 years from the Study of Osteoporotic Fractures (SOF). Participants were determined to have undergone surgical versus natural menopause based on whether or not they reported retrospectively having undergone a bilateral oophorectomy before or after menopause. Frailty status was classified as not frail, somewhat frail (hereafter referred to as Intermediate stage), frail or death at four interviews, conducted 6-18 years post-baseline. Baseline serum total testosterone concentrations were available on a subset of 541 participants. RESULTS: Approximately 12.6% of the participants reported surgical menopause. A total of 39.7% were classified as somewhat frail (intermediate stage) and 10.1% as frail. Twenty-two (22.0%) of the participants died during the interview period when frailty was assessed. Mean age at baseline was 71.2 years. Total serum testosterone levels were significantly lower among surgically menopausal women compared to naturally menopausal women (p<0.01). Surgical menopause was not significantly associated with an increased risk of frailty (Odds Ratio=0.94; 95% CI=0.72-1.22), intermediate stage frailty (Odds Ratio=0.96; 95% CI=0.80-1.10) or death (Odds Ratio=1.17 ; 95% CI=0.97-1.42) after adjusting for age, BMI and number of IADL impairments. Stratified analyses showed that oral estrogen use did not modify these associations. CONCLUSION: Among postmenopausal women, surgical menopause was not associated with a higher risk for frailty compared to naturally menopausal women, even in the absence of estrogen therapy. Future prospective studies are needed to investigate hormonal mechanisms involved in the development of frailty in older postmenopausal women. / 2017-11-05T00:00:00Z

Research that examines gender and retirement has given us insights on the ways in which gender structures the work and retirement experience primarily for white men and women. At the same time, a small but growing body of research on race-ethnicity and retirement reveals that race-ethnicity also serves as a context that structures the work and retirement experience. However, research that examines the intersections of race-ethnicity and gender in relation to retirement is almost non-existent. Our subsequent knowledge of how race-ethnicity and gender serve as contexts defining the retirement experience is severely limited. One result is that it is difficult to make generalizations or draw reliable conclusions concerning non-dominant populations. To address this gap, I conducted an exploratory investigation on the general topic of race, gender, and retirement, specifically focusing on how the process of self-definition as retired occurs among African-American men and women. Using data from Wave I of the Americans' Changing Lives Survey, this investigation identified the gender-and class-specific paid and unpaid productive activities that African-Americans ages fifty-five and older perform. Since unpaid activities are gender-specific, examining them, along with measures of income, income sources, education, marital status, age, and disabled status would help reveal the extent to which gender interacts with race-ethnicity to structure self-definition for Black men and women. These findings suggest that for older African-Americans, gender significantly impacts the decision to self-define as retired. However, when considering the impact of gender-specific unpaid productive activities, the above finding is not true. It is only in relation to the receipt of Social Security income, disabled status, and work status that gender significantly interacts with race-ethnicity to structure the decision to self-define as retired. In general, these findings substantiate pre-existing research on race, gender, and retirement. Importantly, they prompt further development of scholarly literature in this area of research, as this body of literature is still largely underexplored and inconclusive. / Master of Science

High body mass index (BMI) has been found to be associated with a multitude of health issues and its longitudinal effect on mortality needs to be further understood due to increasing rates of obesity. The relationship between BMI and mortality is a key public health concern due to the rise in obesity prevalence and advancing knowledge of the impact of BMI on all aspects of health. In order to expand and further contribute to the understanding of the long-term impact of BMI on mortality, we utilized prospective, longitudinal data from the Veterans Affairs (VA) Normative Aging Study (NAS) to assess the relationship between BMI and 40-year all-cause and cause-specific mortality in men. Cox regression was used to evaluate the relationship between BMI and all-cause and cause-specific (cancer, congenital heart disease (CHD), stroke) mortality. Of the 1,680 men included in this study, the majority were White (96.7%), born between 1920–1929, were between ages 50–59 years, married, completed some college, identified as an occasional drinker and a current smoker, and worked in a “white-collar” job. This study did not identify any men who had an underweight BMI. 594 men had normal BMI, 910 men were overweight, and 176 men were obese. After adjusting for confounders, compared to men with normal BMI, overweight men had higher risk for CHD mortality (HR=1.33, 95% CI, 0.95–1.86), lower risk for all-cause and stroke mortality (HR=0.98, 95% CI, 0.87–1.11, HR=0.88, 95% CI, 0.53–1.45, respectively), and no difference in risk for cancer mortality (HR=1.00, 95% CI, 0.82–1.23). Obese men had higher risk for all-cause and stroke mortality (HR=1.19, 95% CI, 0.98–1.45, HR=1.26, 95% CI, 0.57–2.79, respectively) and lower risk for CHD and cancer mortality (HR=0.87, 95% CI, 0.48–1.58, HR=0.95, 95% CI, 0.68–1.33, respectively). In conclusion, this study found that men categorized as obese had an increased risk of all-cause and stroke mortality, and men categorized as overweight had an increased risk of CHD mortality, compared to those with normal BMI. However, due to all confidence intervals crossing 1.00, there is a suggestion that BMI had an effect on mortality in this sample. These results are limited by selection bias during the NAS screening process which selected for healthy men. This may have skewed our results toward the null, potentially diminishing the association between BMI and mortality.

Twelve-month-old male Sprague-Dawley rats exhibited a marked increase in percent adiposity and percent epididymal fat pad weight compared to their 2-month-old littermates. Aging was accompanied by deteriorated metabolic flexibility including decreased insulin sensitivity to glucose metabolism and increased hepatic lipid deposition. The alterations in adiposity and metabolic flexibility can be due to increased energy intake and/or decreased energy expenditure. Therefore, our first objective was to evaluate the status of energy intake and voluntary and involuntary energy expenditure in the animals. Our results show that food intake and voluntary energy expenditure as measured by locomotor activity were not responsible for the age-induced adiposity. Increased feed efficiency and decreased core body temperature in 12-month-old animals suggested that a reduction in resting metabolic rate (RMR) was responsible for their adiposity. Adaptive thermogenesis is an important component of RMR. We observed decreased mRNA levels of the major thermogenic gene, UCP1 in the brown adipose tissue (BAT) of 12-month-old animals that confirmed literature reports of decreased BAT mediated thermogenesis with age. Recently, subcutaneous white adipose tissue (sWAT) has also been shown to engage in thermogenesis though its contribution to energy expenditure and age mediated adiposity has not been investigated in detail. We hypothesized that decreases in inguinal WAT (IWAT) mediated thermogenesis contributes to the increased adiposity in 12-month-old animals. The next objective of our studies was to explore each step in the pathway of IWAT mediated thermogenesis including sympathetic nervous system (SNS) tone, SNS mediated lipolysis, fatty acid oxidation, mitochondrial biogenesis, and mitochondrial function in 2-month and 12-month-old male Sprague-Dawley rats. We observed decreases in β2-adrenergic receptor mRNA levels and adenylate cyclase activity in 12-month-old animals indicating that aging caused a decline in intracellular SNS tone in IWAT. Decreased SNS tone produced a decrease in the mRNA levels of its downstream target, the rate limiting lipolytic enzyme, hormone sensitive lipase but no change in the expression of the critical fatty acid oxidation gene, CPT1b. Twelve month old animals exhibited decreased mRNA levels of the master regulator of mitochondrial biogenesis, PGC1α, and decreased activity of citrate synthase, a marker of mitochondrial density. Accompanying these decreases in mitochondrial biogenesis was a decrease in mitochondrial function as evidenced by decreased mRNA levels of COX4i1, a marker of mitochondrial oxidative capacity and decreased activity of cytochrome c oxidase, a marker of complex IV activity in the electron transport chain. Finally, twelve month old animals exhibited decreased mitochondrial thermogenic capacity as evidenced by decreased mRNA and protein levels of UCP1. Twelve month animals also exhibited decrease in the complementary thyroid axis mediated thermogenesis evidenced in decreases in plasma levels of thyroxine (T4) and triiodothyronine (T3) and decreased IWAT mRNA and protein levels of Dio2 that will likely result in decreased tissue T3 levels. Overall, our findings indicate that in the IWAT, age is associated with decline in SNS mediated β-AR signaling for lipolysis that results in decreased fuel for thermogenesis. The decrease in fuel is exacerbated by a decreased mitochondrial capacity and function that compromises its ability to convert fuel to heat. Accompanying these reductions is a decrease in IWAT thyroid axis mediated thermogenesis. We conclude that age mediated decline in IWAT thermogenesis contributes to the marked increase in adiposity in male Sprague-Dawley rats.

Cardiac aging leads to increased susceptibility to cardiovascular diseases due to compromised structure and function of the heart. Aging is characterized by a series of complex physiological, cellular, and molecular changes. Cellular senescence, a hallmark of aging, is attributed to stable and permanent cell cycle arrest by several molecular activation mechanisms. Growing evidence indicates that cellular senescence plays an important role in the pathophysiology of age-associated cardiac diseases, which is often related to the accumulation of senescent cells within the heart due to aging. Several factors such as epigenetic dysregulation, cell cycle dysregulation, and increased DNA damage are the changes observed in the cells that lead to senescence physiological processes. Increasing evidence suggests that epigenetic-regulating genes have a significant role in cellular senescence-activating pathways. B cell-specific Moloney murine leukemia virus integration site 1(BMI-1) is an epigenetic regulator that has been associated with biological processes including proliferation, development, and differentiation. However, the effect of BMI1 as a regulator of cardiac structure and function remains to be understood. This study explores the role of BMI1 expression in the heart during aging, in validating cellular senescence. Also, the role of BMI1 expression in the heart in regard to promoting premature senescence in an aging heart with and without cardiac injury. BMI1 expression levels in heart cells from aged global Bmi1 mice models are measured using Real-Time Quantitative Polymerase Chain Reaction (RT- qPCR) and western blotting. We hypothesize that the involvement of epigenetic regulation genes such as BMI1 are necessary in mediating cellular senescence during aging. In addition, the loss of BMI1 expression is shown to induce the senescence-activating pathway promoting premature senescence in cardiac aging. Taken together, these studies suggest that epigenetic involving signaling mechanisms play an important role in cellular senescence during cardiac aging. And it could open promising targets for novel therapeutic avenues during the aging process. / Biomedical Sciences

Thesis (M.S.P.H.)--University of Michigan, 1940. / Cover title: Problems of an aging population.

Thesis (Ph. D.)--Florida State University, 2005. / Advisor: Dr. E. Jane Burkhead, Florida State University, College of Education, Dept of Educational Psychology and Learning Systems. Title and description from dissertation home page (viewed June 14, 2005). Document formatted into pages; contains xiii, 203 pages. Includes bibliographical references.

Thesis (M.S.P.H.)--University of Michigan, 1940. / Cover title: Problems of an aging population.