Our Research
The Integrative Physiology of Aging laboratory conducts translational research to improve human healthspan. Below are the current and ongoing NIH-funded clinical and preclinical studies in the laboratory. Each study listed includes the project name, grant number, and project narrative.
Please click the grant number for a given study to read additional information on NIHRePORTER or click here for a list of our ongoing clinical trials (and their outcome measures and eligibility criteria) on ClinicalTrials.gov.
For a history of laboratory funding over its 35+ years of operation, please click here.
Nicotinamide riboside supplementation for treating elevated systolic blood pressure and improving vascular function in mid-life and older adults
Project Narrative: Age-related increases in clinic and 24-hour systolic blood pressure (SBP) and arterial stiffness are strong independent predictors of heart disease, stroke, cognitive impairments/dementia and other chronic disorders of aging. This phase IIa clinical trial seeks to establish the safety and efficacy of nicotinamide riboside, a natural supplement that increases the bioavailability of NAD+ (a co-enzyme/co-substrate critical for cellular metabolic function), for lowering clinic and 24-hour SBP and aortic stiffness in middle-aged and older adults with increased initial SBP (high blood pressure).
Passive heat therapy for lowering systolic blood pressure and improving vascular function in mid-life and older adults
Project Narrative: Age-related increases in systolic blood pressure (SBP) and impaired artery function are major risk factors for cardiovascular diseases (CVD), stroke, cognitive impairments and dementia in “mid-life” (50-64 years) and older (65+ years) (ML/O) adults, especially in those ML/O adults with SBP in the ranges of “elevated” SBP (120-129 mmHg) and stage 1 hypertension (SBP 130-139 mmHg). We propose to conduct a clinical trial to assess the effectiveness and safety of “passive heat therapy” (repeated hot tub use) vs. “sham” (repeated sitting in water set to normal body temperature) for decreasing SBP and improving artery function in ML/O adults with elevated SBP or stage 1 hypertension. We will also gain insight into the molecular mechanisms underlying these potential effects of passive heat therapy, and whether the effects of heat therapy can last for up to 12 weeks after stopping hot tub sessions.
Inspiratory muscle strength training for lowering systolic blood pressure and improving endothelial function in postmenopausal women: comparison with “standard of care” aerobic exercise
Project Narrative: Estrogen-deficient postmenopausal (PME-) individuals exhibit a rapid increase in systolic blood pressure (SBP) which is associated with vascular endothelial dysfunction and increased risk for cardiovascular diseases. Aerobic exercise (AE), a standard-of-care treatment for improving cardiovascular health, has modest effects on SBP and does not consistently improve endothelial function in PME- individuals, and is associated with poor adherence. This clinical trial seeks to establish the efficacy of high-resistance inspiratory muscle strength training, a time- and effort-efficient lifestyle intervention, for lowering SBP and improving vascular endothelial function in PME- individuals compared to standard-of-care AE training.
Inspiratory muscle strength training for lowering systolic blood pressure and improving endothelial function in postmenopausal women: comparison with “standard of care” aerobic exercise: Alzheimer’s Disease and Related Dementia Supplement
Project Narrative: Postmenopausal (PM) individuals with above-normal systolic blood pressure (SBP) are at a disproportionate risk for mild cognitive impairment, Alzheimer’s disease and related dementias. Aerobic exercise, a lifestyle intervention for decreasing dementia risk, has modest effects on SBP and may not improve cerebrovascular function in PM individuals, and is associated with poor adherence. This administrative supplement seeks to establish the efficacy of high-resistance inspiratory muscle strength training, a time- and effort-efficient lifestyle intervention, for improving cognitive and cerebrovascular function when compared to aerobic exercise training in asymptomatic, at-risk PM individuals with above-normal initial SBP.
Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans
Project Narrative: Aging is associated with the development of vascular dysfunction, which increases the risk for cardiovascular disease. This clinical trial will determine whether a new oral supplement called MitoQ, which reduces the production of damaging reactive oxygen species from mitochondria, can improve vascular function in older adults, and will provide insight into the biological reasons (mechanisms) by which supplementation with MitoQ exerts these benefits. Overall, this research will provide scientific evidence supporting the use of MitoQ for preserving vascular function and decreasing cardiovascular disease risk with aging.
Feasibility and design of a novel smartphone app to deliver blood pressure-lowering inspiratory muscle strength training
Project Narrative: Above-normal systolic blood pressure (SBP; ≥120 mmHg) is associated with an increased risk for cardiovascular diseases. We recently established the clinical efficacy of high-resistance inspiratory muscle strength training (IMST), a novel form of physical training with minimal barriers to adherence, for lowering SBP in a clinical trial with regular clinic-based, researcher-supervised training. This Phase I STTR application seeks to leverage the growing field of digital health technologies by taking the first steps in developing a feasible and acceptable smartphone app for commercialization that independently guides users through a high-resistance IMST program, a key step to translate IMST for widespread use and improving public health.
Preclinical Studies:
Role of cellular senescence in cardiovascular aging
Project Narrative: We will determine the level of cellular senescence in the heart and arteries from mice undergoing stress-induced senescence, as well as in natural aging. We will evaluate how cellular senescence drives cardiotoxic outcomes at both cell and tissue specific levels as well as establishing gene and protein specific signatures of cell types involved in cardiovascular senescence. Finally, we will evaluate how closely signatures of senescence established in the mouse mirror those seen in aging humans through a novel translational aim.
Targeting cellular senescence to prevent accelerated vascular aging induced by the common chemotherapeutic agent doxorubicin
Project Narrative: Impaired vascular function is a major risk factor for cardiovascular diseases with advancing age and in young adult men and women who have undergone cancer treatment with Doxorubicin chemotherapy. In the proposed project, we will investigate the role of cellular senescence in mediating accelerated vascular aging with Doxorubicin in preclinical mouse models and in vascular cell culture. Overall, the findings of this project have the potential to identify cellular senescence as a novel therapeutic target for preventing/treating impaired vascular function with Doxorubicin and thereby reducing risk of cardiovascular diseases.
DMB (3,3-dimethyl-1-butanol) as a novel translational strategy for preventing and treating gut dysbiosis-associated arterial aging
Project Narrative: The risk of developing cardiovascular diseases increases with aging largely due to age-related declines in the function of arteries (arterial dysfunction), which are mediated primarily by oxidative stress. This study will investigate the potential of a novel food-derived compound, 3,3-dimethyl-1-butanol (DMB), which prevents bacteria in the gut from producing the adverse atherosclerosis-linked metabolite trimethylamine N-oxide (TMAO), for preventing and reversing the development of arterial dysfunction with aging. Overall, this research has the potential to identify a new therapeutic strategy—with great promise for translation to humans—for preventing age-related arterial oxidative stress and dysfunction, thereby reducing risk of age-related cardiovascular diseases.