My research program lies at the intersection between metabolism, reproductive biology and geroscience. I am particularly interested in the role that sex hormones play in regulating aging and disease due to sex-specific disparities in metabolic disease, inflammatory disorders, and healthspan across the life-cycle.
My lab studies the way sex hormones such as estrogen and testosterone impact chronic diseases. We know certain diseases appear and develop differently in males and females, so we study what could be causing this difference. Because the frequency of these sex-dependent diseases balance out after females reach menopause, we can guess at least part of the cause is connected to the hormones produced by the ovaries. My lab focuses on testing the impact of these ovarian hormones on disease models to better understand how to treat these sex-dependent chronic diseases in the future. My long-term goal is to develop therapeutic strategies that target metabolic signaling pathways in a manner similar to calorie restriction, thereby diminishing age-related diseases and compressing the period of morbidity in mid-to-late life.
In my lab, we are interested in unraveling what role sex hormones and their receptors play in the emergence and progression of chronic diseases. We are also particularly interested in understanding sexually dimorphic mechanisms of chronic disease. An example of this is the fact that middle-aged males more commonly develop metabolic disturbances (e.g. glucose intolerance, insulin resistance, diabetes) and chronic liver diseases (e.g. NAFLD, NASH) as compared to age-matched females. Interestingly, these differences in disease prevalence normalize as females undergo menopause. This observation implies that functional ovaries produce endocrine factors (estrogens, miRNA) that elicit systemic beneficial effects, which is generally accepted at this point. However, several poorly understood and underexplored areas of study remain barriers to progress, including:
- Does delaying female reproductive senescence attenuate systemic hallmarks of aging?
- What are the cell-type-specific mechanisms that promote ovarian aging/insufficiency/failure?
- Can ovarian aging be targeted by pharmacological interventions?
- Can the beneficial effects of estrogens and/or estrogen receptor activity be harnessed to treat male-dominant chronic diseases in the absence of deleterious off-target effects?
- Can tissue-specific estrogen receptor agonism delay aging hallmarks in males?
To address these questions, my laboratory employs a number of models and approaches ranging from primary cell culture, transgenic rodents, stereotaxic delivery of AAV viral vectors, in vivo metabolic assessments, molecular biology, and various cytometry techniques. My group also collaboratives extensively with investigators around the globe who assist with various aspects of our current projects, evolving projects and translational studies.
B.S., Bowling Green State University, Bowling Green, Ohio, 2001
M.A., University of Central Florida, Orlando, Florida, 2005
Ph.D., Ohio State University, Columbus, Ohio, 2011
Honors and Awards
Provost’s Research Award for Junior Faculty, OUHSC, 2021
Faculty Excellence in Research Award – College of Allied Health, OUHSC, 2020
Editor’s Choice Manuscript Award, Journal of Gerontology, Biological Sciences, 2017
NIA Summer Training Course Invitee – Aging Research Fellowship, 2015
Gordon Research Conference/Seminar – Postdoctoral Research Fellowship Travel Award, 2015
NIH Loan Repayment Program Awardee, NIA, 2013-2015
4th Alliance for Healthy Aging Symposia – Postdoctoral Research Fellowship Travel Award, 2013
Gordon Research Conference/Seminar – Postdoctoral Research Fellowship Travel Award, 2013
Ad hoc Reviewer – UAB Nathan Shock Center Pilot Grant Review Panel, Spring 2021
Ad hoc Reviewer – College of Allied Health, PHF New Investigator Grant Review Panel, Spring 2019-2021
Ad hoc Reviewer – NIH/NIA Study Section, Special Emphasis Panel ZAG1 ZIJ-D (M1), Spring 2021
Ad hoc Reviewer – College of Medicine, Seed Grant Review Panel, Spring 2019, 2020
Ad hoc Reviewer – Office of Research Administration, PHFGrant Review Panel, Spring 2019, 2020
Manuscript Reviewer - Adipocyte, Biomedicine & Pharmacotherapy, Growth Hormone & IGF Research, Geroscience, Mechanisms of Ageing and Development, Nature Communications, Obesity Research & Clinical Practice, Proceedings of the National Academy of Sciences, Steroids, Translational Psychiatry, US Endocrinology
American Aging Association (AGE)
Gerontological Society of America (GSA)
American Association for the Advancement of Science
American Physiological Society
Joined OMRF Scientific Staff in 2021.
Isola JVV, Zanini BM, Hense JD, Alvarado-Rincón JA, Garcia DN, Pereira GC, Vieira AD, Oliveira TL, Collares T, Gasperin BG, Stout MB, Schneider A. Mild calorie restriction, but not 17α-estradiol, extends ovarian reserve and fertility in female mice. Exp Gerontol 159:111669, 2022 January, PMID: 35032571
Wu D, Eeda V, Undi RB, Mann S, Stout M, Lim HY, Wang W. A Novel Peroxisome Proliferator-Activated Receptor Gamma Ligand Improves Insulin Sensitivity and Promotes Browning of White Adipose Tissue in Obese Mice. Mol Metab:101363, 2021 October, PMID: 34710641, PMCID: PMC8627988
Ansere V, Ali-Mondal S, Sathiaseelan R, Saccon TD, Garcia DN, Isola JVV, Hense JD, Ocañas SR, Buettner KB, Stout MB, Schneider A, Freeman WM. Cellular hallmarks of aging emerge in the ovary prior to primordial follicle exhaustion. Mech. Ageing Dev. 194:111425, 2020. PMID: 33383072, PMCID: PMC8279026
Isola JVV, Zanini BM, Sidhom S, Kopchick JJ, Bartke A, Masternak MM, Stout MB, Shneider A. 17α-estradiol promotes ovarian aging in growth hormone receptor knockout mice, but not wild-type littermates. Exp. Gerontol. 129:110769, 2020. PMID: 31698046, PMCID: PMC6911620
Mann SN, Pitel KS, Nelson-Holte MH, Iwaniec UT, Turner RT, Sathiaseelan R, Kirkland JL, Schneider A, Morris KT, Malayannan S, Hawse JR, Stout MB. 17α-estradiol prevents ovariectomy-mediated obesity and bone loss. Exp. Gerontol. 142:111113, 2020. PMID: 33065227, PMCID: PMC8351143
Mann SN, Hadad N, Nelson-Holte MH, Rothman AR, Sathiaseelan R, Mondal SA, Agbaga M-P, Unnikrishnan A, Subramaniam M, Hawse JR, Huffman DM, Freeman WM, Stout MB. Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife. 8;9:e59616, 2020. PMID: 33289482, PMCID: PMC7744101
Steyn FJ, Ngo ST, Chen VP, Bailey-Downs LC, Xie TY, Ghdami M, Brimijoin S, Freeman WM, Rubinstein M, Low MJ, Stout MB. 17α-estradiol acts through hypothalamic pro-opiomelanocortin expressing neurons to reduce feeding behavior. Aging Cell. 17(1): e12703, 2018. PMID: 29168299, PMCID: PMC5770854
Stout MB, Steyn FJ, Jurczak MJ, Camporez JPG, Zhu Y, Hawse JR, Jurk D, Palmer AK, Xu M, Pirtskhalava T, Evans GL, Santos RDS, Frank AP, White TA, Monroe DG, Singh RJ, Verzosa GC, Miller JD, Clegg DJ, LeBrasseur NK, von Zglinicki T, Shulman GI, Tchkonia T, Kirkland JL. Late-life administration of 17α-estradiol alleviates metabolic and inflammatory dysfunction without inducing feminization. J. Gerontol. A. Biol. Sci. Med. Sci. 72(1):3-15, 2017. PMID: 26809497, PMCID: PMC5155656