Research Interests:
- The central focus of Dr. Stout’s research program is to understand how metabolic disturbances promote aging processes and the onset of chronic diseases. He is 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. The long-term goal of Dr. Stout’s laboratory 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.
Funding:
Selected funding, see CV for complete list
- Cellular senescence and epigenomic remodeling in ovarian aging
Agency: NIH/NIA
Type: R01 [AG069742]
Amount: $1,250,000 (direct)
Period: September 2020-May 2025
Role: PI
- Mechanisms of metabolic, inflammatory, and healthspan enhancement by 17α-estradiol
Agency: NIH/NIA
Type: K99/R00 [AG051661]
Amount: $1,024,528 (direct)
Period: September 2016-May 2021
Role: PI
Select Publications:
Selected publications, see CV for complete list:
- 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. 2020. In Press
- Chucair-Elliott AJ, Ocanas SR, Stanford DR, Ansere VA, Buettner KB, Porter H, Eliason NL, Reid J, Sharpe AL, Stout MB, Beckstead MJ, Miller BF, Richardson A, Freeman WM. Inducible cell-specific mouse models for paired epigenetic and transcriptomic studies of microglia and astroglia. Commun. Biol. 2020. In Press
- Sidhom S, Schneider A, Fang Y, McFadden S, Darcy J, Sathiaseelan R, Palmer AK, Steyn FJ, Grillari J, Kopchick JJ, Bartke A, Siddiqi S, Masternak MM, Stout MB. 17α-estradiol modulates IGF1 and hepatic gene expression in a sex-specific manner. J. Gerontol. A. Biol. Sci. Med. Sci. 2020. In Press
- Miller BF, Pharaoh G, Hamilton KL, Peelor FF III, Kirkland JL, Freeman WM, Mann SN, Kinter M, Price JC, Stout MB. Short-term calorie restriction and 17α-estradiol administration elicit divergent effects on proteostatic processes and protein content in metabolically active tissues. J. Gerontol. A. Biol. Sci. Med. Sci. 75(5):849-857, 2020.
- Palmer AK, Xu M, Zhu Y, Pirtskhalava T, Weivoda MM, Hachfeld CM, Prata LG, van Dijk TH, Verkade E, Casaclang-Verzosa G, Johnson KO, Cubro H, Doornebal EJ, Ogrodnik M, Jurk D, Jensen MD, Chini EN, Miller JD, Matveyenko A, Stout MB, Schafer MJ, White TA, Hickson LJ, Demaria M, Garovic V, Grande J, Arriaga E, Kuipers F, von Zglinicki T, LeBrasseur NK, Campisi J, Tchkonia T, Kirkland JL. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell. 18(3):e12950, 2019
- 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.
- Stout MB, Justice JN, Nicklas BJ, Kirkland JL. Physiological aging: Links among adipose tissue dysfunction, diabetes, and frailty. Physiology. 32(1):9-19, 2017.
- 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.
- Schafer MJ, White TA, Evans G, Tonne JM, Verzosa GC, Stout MB, Mazula DL, Palmer AK, Baker DJ, Jensen MD, Torbenson MS, Miller JD, Ikeda Y, Tchkonia T, van Deursen JM, Kirkland JL, LeBrasseur NK. Exercise prevents diet-induced cellular senescence in adipose tissue. Diabetes. 65(6):1606-1615, 2016.
- Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, Dai HM, Ling YY, Stout MB, Pirtskhalava T, Giorgadze N, Johnson KO, Giles CB, Wren JD, Niedernhofer LJ, Robbins PD, Kirkland JL. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell. 15(3):428-435, 2016.
- Xu M, Palmer AK, Ding H, Weivoda MW, Pirtskhalava T, White TA, Sepe A, Johnson KO, Stout MB, Giorgadze N, Jensen MD, LeBrasseur NK, Tchkonia T, Kirkland JL. Targeting senescent cells enhances adipogenesis and metabolic function in old age. Elife. 19(4):e12997, 2015.
- Xu M, Tchkonia T, Ding H, Ogrodnik M, Lubbers ER, Pirtskhalava T, White TA, Johnson KO, Stout MB, Mezera V, Giorgadze N, Jensen MD, LeBrasseur NK, Kirkland JL. JAK inhibition alleviates the cellular senescent-associated secretory phenotype and frailty in old age. Proc. Natl. Acad. Sci. USA. 112(46):E6301-E6310, 2015.
- Stout MB, Swindell WR, Zhi X, Rohde K, List EO, Berryman DE, Kopchick JJ, Gesing A, Fang Y, Masternak MM. Transcriptome profiling reveals divergent expression shifts in brown and white adipose tissue from long-lived GHRKO mice. Oncotarget. 6(29):26702-26715, 2015.
- Zhu Y, Tchkonia T, Pirtskhalava T, Gower A, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Borden G, Lenburg M, O’Hara SP, LaRusso NF, Miller JD, Roos CM, Verzosa GC, LeBrasseur NK, Wren JD, Farr JN, Khosla S, Stout MB, McGowan SJ, Fuhrmann-Stroissnigg H, Gurkar AU, Zhao J, Colangelo D, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Niedernhofer LJ, Kirkland JL. The achilles’ heel of senescent cells: From transcriptome to senolytic drugs. Aging Cell. 14(4):644-658, 2015.
- Stout MB, Tchkonia T, Pirtskhalava T, Palmer AK, List EO, Berryman DE, Lubbers ER, Escande C, Spong A, Masternak MM, Oberg AL, LeBrasseur NK, Miller RA, Kopchick JJ, Bartke A, Kirkland JL. Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice. Aging. 6(7):575-586, 2014.