Genetic Evaluation and Modification of Lifestyles to Improve Female Life Expectancy

The long-term goal of this research is to create and implement lifestyle interventions that will prevent or delay morbidities associated with accelerated aging in the menopausal women. By the end of this year, it is estimated that approximately 50 million women will be in the menopausal phase of their life. Menopause is defined by the decline in estrogen levels and subsequent increase in inflammatory markers which are associated with multiple morbidities involving the brain, bone and cardiovascular systems. Various lifestyle changes have been found to prevent or decrease these morbidities. Hormone replacement therapy in the early years of menopause is also a known therapeutic modality for the treatment of menopausal symptoms. The investigators will evaluate if hormone replacement and lifestyle change will have an enhanced effect on the prevention of morbidity and mortality.

Telomeres are distinct structures found at the end of chromosomes. As women enter into menopause, which is the biomarker for aging, there is a shortening of the telomere length. Poor lifestyle factors which cause oxidative stress, can lead to poor cell replication and critical shortening of telomere length. Telomerase, an enzyme which aids in gene sequencing, also declines. Shortened telomere length and low levels of telomerase lead to cell aging and apoptosis, a reduction in normal organ function, and an increase in morbidity and mortality. It has been found that lifestyle intervention, and possibly hormone replacement, can enhance telomere length and telomerase production.

This research will focus on the acute menopausal woman (within 5 years of the last menstrual period), with and without hormone replacement, .and multiple lifestyle interventions. Early intervention within the first five years of menopause is most important in affecting long term morbidity and mortality in women. Serial measurement of various biomarkers and cytokines associated with aging, and measurements of telomere length and telomerase levels will be performed over a 9 month period of time. Evidence shows that diet, physical activity and cognitive intervention may synergize when combined in a multimodal intervention as each targets different mechanisms. The Investigators will evaluate the efficacy of each 12-week interventions on telomere length, telomere production, serum biomarkers and cytokine levels before and after each intervention, and as a multimodal approach. Approximately 100 women will be recruited once they have been confirmed to be in the early stages of menopause, then further divided based on the use of hormone replacement. Aims are to: (1) determine the independent and combined efficacies of lifestyle interventions on telomere length, (2) determine the independent and combined efficacies of lifestyle interventions on biomarkers and and cytokines, (3) Determine other mechanisms of aging associated with the acute phase of menopause . This key knowledge will aid in practical and early lifestyle interventions to deter detrimental morbidities in the menopausal women.