The Hepple lab focuses on aging and age-related diseases/conditions, with a primary focus on skeletal muscle, the mitochondria therein, and bidirectional interactions between muscle and the systemic milieu.
Our research
Our current work is divided between a large human cohort study called the Study of Muscle, Mobility and Aging (SOMMA), and fundamental science aimed at understanding the mechanisms by which mitochondria drive skeletal muscle alterations with aging and diseases/conditions associated with aging.
The overall goal of SOMMA is to understand what role skeletal muscle biology plays in mobility decline, including mobility disability (inability to walk 400m unassisted within 15 min), age-related morbidity and death.
For our fundamental science we are primarily focused on understanding what role an event known as mitochondrial permeability transition (mPT) plays in driving muscle pathology seen with cancer cachexia and sepsis, and in mediating retrograde signaling from muscle that exacerbates systemic inflammation and cognitive impairment in sepsis, and Alzheimer’s disease and other dementias.
Lab members
Sung Gi Noh
Publications
- S.K. Skinner, A. Solania, D.W. Wolan, M.S. Cohen, T.E. Ryan and R.T. Hepple. Mitochondrial permeability transition causes mitochondrial reactive oxygen species- and caspase 3-depedent atrophy of single adult mouse skeletal muscle fibers. Cells 10(1): 2586, 2021.
- C. Lukasiewicz, G.J. Tranah, D.S. Evans, P.M. Coen, H.N. Barnes, Z. Huo, K.A. Esser, N.E Lane, S.B. Kritchevsky, S.R. Cummings, P.M. Cawthon and R.T. Hepple. Higher expression of denervation-responsive genes is negatively associated with muscle volume and performance traits in the study of muscle, mobility and aging (SOMMA). Aging Cell 23(6): e14115, 2024.
- C. Ubaida-Mohien, R. Moaddel, S. Spendiff, N.J. MacMillan, M.E. Filion, J.A. Morais, J. Candia, L.F. Fitzzgerald, T. Taivassalo, P.M. Coen, L. Ferrucci, and R.T. Hepple. Serum proteomic and metabolic signatures of high versus low physical function in octogenarians. Aging Cell 24(5): e70002, 2024.
- T. Thome, K. Miguez, A.J. Willms, S.K. Burke, V. Chandran, A.R. de Souza, L.F. Fitzerald, C. Baglole, M.E. Anagnostou, J. Bourbeau, R.T. Jagoe, J.A. Morais, Y. Goddard, T. Taivassalo, T.E. Ryan and R.T. Hepple. Chronic aryl hydrocarbon receptor activity phenocopies smoking-induced skeletal muscle impairment. J Cachexia Sarcopenia Muscle 13(1): 589-604, 2022.
- S.K. Skinner, A.I. Fenton, Y. Konokhova, R.T. Hepple. Variation in muscle and neuromuscular junction morphology between atrophy-resistant and atrophy-prone muscles supports failed reinnevation in aging muscle atrophy. Exp Gerontol. 156: 111613, 2021.
- V. Sonjak, K. Jacob, J.A. Morais, M. Rivera-Zengotita, S. Spendiff, C. Spake, T. Taivassalo, S. Chevalier, and R.T. Hepple. Fidelity of muscle fibre reinnervation modulates ageing muscle impact in elderly women. J Physiol. 597(19): 5009-23, 2019.
- D. Neyroud, R.L. Nosacka, A.R. Judge, and R.T. Hepple. Colon 26 adenocarcinoma (C26)-induced cancer cachexia impairs skeletal muscle mitochondrial function and content. J Muscle Res Cell Motil. 40(1): 59-65, 2019.
- M. Semel, C. Lukasiewicz and R.T. Hepple. Novel insights to mitochondrial impact in aging skeletal muscle. Exerc Sport Sci Rev. 53(3): 101-09, 2025.
- A.B. Newman, T.L. Blackwell, T. Mau, P.M. Cawthon, P.M. Coen, S.R. Cummings, F.G.S. Toledo, B.H. Goodpaster, N.W. Glynn, R.T. Hepple, and S.B. Kritchevsky. Vigor to frailty as a continuum – A new approach in the study of muscle, mobility and aging (SOMMA). J Gerontol A Biol Sci Med Sci. 79(1): glad244, 2024.
- K.D. Wimberly, M.Y. Kawaida, A.L. Tice, X. Luo, J.A. Lackey, S. Alvarez, L. Wei-LaPierre, R.T. Hepple, and T.E. Ryan. Mitochondrial diagnostics reveal diffuse impairments in skeletal muscle energetics in aging mice. J Appl Physiol. 139(3): 839-848, 2025.
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