Anthony J. Donato

Anthony J. Donato, PhD, MS

Languages spoken: English

Academic Information

Departments Primary - Internal Medicine

Divisions: Geriatrics

My primary research focus is vascular aging, in particular the cellular, molecular and tissue specific events that induce reductions in muscle blood flow during exercise, impair arterial endothelial function and stiffen large elastic arteries in older rodents/adults. These vascular phenotypes contribute to the age related decline in functional capacity and the development of cardiovascular disease, and can be ameliorated by lifestyle interventions such as habitual exercise and caloric restriction. My secondary focus, is to elucidate the cellular pathways which confer the vaso-protective effects of these lifestyle interventions and try to activate these pathways pharmacologically to see if this will confer some of the same benefits. I have used human, rodent, and cell models to address these questions and utilized a wide range of contemporary translational experimental techniques from microRNA gene expression to ultrasonography to investigate the aforementioned interests.

Education History

Undergraduate University of Colorado, Boulder
 BA
Graduate Training University of Colorado, Boulder
 MS
Doctoral Training Texas A&M University
 PhD
Postdoctoral Fellowship University of California at San Diego, Department of Medicine, Dr. Russell Richardson
 Postdoctoral Fellow
Postdoctoral Fellowship University of Colorado, Department of Integrative Physiology
 Postdoctoral Fellow

Selected Publications

Journal Article

  1. Walker AE, Kronquist EK, Chinen KT, Reihl KD, Li DY, Lesniewski LA, Donato A (2019). Cerebral and skeletal muscle feed artery vasoconstrictor responses in a mouse model with greater large elastic artery stiffness. Experimental physiology, 104(3), 434-442.
  2. Islam MT, Henson GD, Machin DR, Bramwell RC, Donato AJ, Lesniewski L (2020). Aging differentially impacts vasodilation and angiogenesis in arteries from the white and brown adipose tissues. Experimental gerontology, 142, 111126.
  3. Yuen LH, Dana S, Liu Y, Bloom SI, Thorsell AG, Neri D, Donato AJ, Kireev D, Schüler H, Franzini R (2019). A Focused DNA-Encoded Chemical Library for the Discovery of Inhibitors of NAD+-Dependent Enzymes. Journal of the American Chemical Society, 141(13), 5169-5181.
  4. Trott DW, Machin DR, Phuong TT, Adeyemo AO, Bloom SI, Bramwell RC, Sorensen ES, Lesniewski LA, Donato A (2021). T cells mediate cell non-autonomous arterial aging in mice. The Journal of physiology, 599, 3973-3991.
  5. Phuong TTT, Walker AE, Henson GD, Machin DR, Li DY, Donato AJ, Lesniewski L (2019). Deletion of Robo4 prevents high-fat diet-induced adipose artery and systemic metabolic dysfunction. Microcirculation (New York, N.Y., 26(5), e12540.
  6. Hazra S, Henson GD, Bramwell RC, Donato AJ, Lesniewski L (2019). Impact of high-fat diet on vasoconstrictor reactivity of white and brown adipose tissue resistance arteries. American journal of physiology. Heart and circulatory physiology, 316(3), H485-H494.
  7. Machin DR, Phuong TT, Donato A (2019). The role of the endothelial glycocalyx in advanced age and cardiovascular disease. Current opinion in pharmacology, 45, 66-71.
  8. Machin DR, Auduong Y, Gogulamudi VR, Liu Y, Islam MT, Lesniewski LA, Donato A (2020). Lifelong SIRT-1 overexpression attenuates large artery stiffening with advancing age. Aging, 12(12), 11314-11324.
  9. Walker AE, Breevoort SR, Durrant JR, Liu Y, Machin DR, Dobson PS, Nielson EI, Meza AJ, Islam MT, Donato AJ, Lesniewski L (2019). The pro-atherogenic response to disturbed blood flow is increased by a western diet, but not by old age. Scientific reports, 9(1), 2925.
  10. Ait-Aissa K, Blaszak SC, Beutner G, Tsaih SW, Morgan G, Santos JH, Flister MJ, Joyce DL, Camara AKS, Gutterman DD, Donato AJ, Porter GA Jr, Beyer A (2019). Mitochondrial Oxidative Phosphorylation defect in the Heart of Subjects with Coronary Artery Disease. Scientific reports, 9(1), 7623.
  11. Trott DW, Islam MT, Buckley DJ, Donato AJ, Dutson T, Sorensen ES, Cai J, Gogulamudi VR, Phuong TTT, Lesniewski L (2021). T lymphocyte depletion ameliorates age-related metabolic impairments in mice. GeroScience, 43(3), 1331-1347.
  12. Machin DR, Clifton HL, Wray DW, Frech TM, Donato A (2022). Tetrahydrobiopterin Administration Augments Exercise-Induced Hyperemia and Endothelial Function in Patients With Systemic Sclerosis. Frontiers in medicine, 8, 791689.
  13. Pierce GL, Coutinho TA, DuBose LE, Donato A (2021). Is It Good to Have a Stiff Aorta with Aging? Causes and Consequences. Physiology (Bethesda, Md.),
  14. Bloom SI, Liu Y, Tucker JR, Islam MT, Machin DR, Abdeahad H, Thomas TG, Bramwell RC, Lesniewski LA, Donato A (2023). Endothelial cell telomere dysfunction induces senescence and results in vascular and metabolic impairments. Aging cell, 22(8), e13875.
  15. Gogulamudi VR, Islam MT, Durrant JR, Adeyemo AO, Trott DW, Hyuhn MH, Zhu W, Donato AJ, Walker AE, Lesniewski L (2023). Heterozygosity for ADP-ribosylation factor 6 suppresses the burden and severity of atherosclerosis. PloS one, 18(5), e0285253.
  16. Lim J, Machin DR, Donato A (2023). The role of hyaluronan in endothelial glycocalyx and potential preventative lifestyle strategy with advancing age. Current topics in membranes, 91, 139-156.
  17. Frech TM, Maguire C, Petrey AC, Stoddard GJ, Donato A (2022). A systemic sclerosis disease model: can inducible pluripotent stem cells fill an unmet need in defining vascular leak?. Rheumatology (Oxford, England),
  18. Mankouski A, Miller TA, Dodson RB, Yu B, Yang Y, Liu J, Machin DR, Donato AJ, McKnight RA, Zinkhan E (2022). Large artery stiffening and mortality in a rat model of early vascular remodeling induced by intrauterine growth restriction and a high-fat diet. Physiological reports, 10(23), e15518.
  19. Bloom SI, Tucker JR, Lim J, Thomas TG, Stoddard GJ, Lesniewski LA, Donato A (2022). Aging results in DNA damage and telomere dysfunction that is greater in endothelial versus vascular smooth muscle cells and is exacerbated in atheroprone regions. GeroScience, 44(6), 2741-2755.
  20. Gogulamudi VR, Machin DR, Henson GD, Lim J, Bramwell RC, Durrant JR, Donato AJ, Lesniewski L (2022). Sirt1 overexpression attenuates Western-style diet-induced aortic stiffening in mice. Physiological reports, 10(9), e15284.
  21. Islam MT, Tuday E, Allen S, Kim J, Trott DW, Holland WL, Donato AJ, Lesniewski L (2023). Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age. Aging cell, 22(2), e13767.
  22. Machin DR, Trott DW, Gogulamudi VR, Islam MT, Bloom SI, Vink H, Lesniewski LA, Donato A (2023). Glycocalyx-targeted therapy ameliorates age-related arterial dysfunction. GeroScience,
  23. Venturelli M, Morgan GR, Tarperi C, Zhao J, Naro F, Reggiani C, Donato AJ, Richardson RS, Schena (2024). Physiological determinants of mechanical efficiency during advanced ageing and disuse. The Journal of physiology, 602(2), 355-372.
  24. Gimblet CJ, Ernst JW, Bos KD, Stroud AK, Donato AJ, Jalal DI, Pierce G (2023). Effect of acute heparin administration on glycocalyx thickness and endothelial function in healthy younger adults. Journal of applied physiology,
  25. Islam MT, Hall SA, Dutson T, Bloom SI, Bramwell RC, Kim J, Tucker JR, Machin DR, Donato AJ, Lesniewski L (2023). Endothelial cell-specific reduction in mTOR ameliorates age-related arterial and metabolic dysfunction. Aging cell, 23(2), e14040.
  26. Bloom SI, Tucker JR, Machin DR, Abdeahad H, Adeyemo AO, Thomas TG, Bramwell RC, Lesniewski LA, Donato A (2023). Reduction of double-strand DNA break repair exacerbates vascular aging. Aging, 15(19), 9913-9947.
  27. Islam MT, Cai J, Allen S, Moreno DG, Bloom SI, Bramwell RC, Mitton J, Horn AG, Zhu W, Donato AJ, Holland WL, Lesniewski L (2024). Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice. Arteriosclerosis, thrombosis, and vascular biology, 44(5), 1101-1113.
  28. Gimblet CJ, Ernst JW, Bell B, Bos KD, Stroud AK, Wendt LH, Donato AJ, Jalal DI, Pierce G (2024). Effect of glycocalyx-targeted therapy on vascular function in older adults: a randomized controlled trial. Journal of applied physiology, 136(6), 1488-1495.
  29. Islam MT, Cai J, Allen S, Moreno DG, Bloom SI, Bramwell RC, Mitton J, Horn AG, Zhu W, Donato AJ, Holland WL, Lesniewski L (2023). Endothelial specific reduction in Arf6 impairs insulin-stimulated vasodilation and skeletal muscle blood flow resulting in systemic insulin resistance. bioRxiv,
  30. Bloom SI, Tuday E, Islam T, Gogulamudi VR, Lesniewski LA, Donato A (2023). Senolytics Reduce Endothelial Cell DNA Damage and Telomere Dysfunction Despite Reductions in Telomere Length. Aging biology, 1,
  31. Gimblet CJ, Donato AJ, Jalal DI, Pierce G (2025). Sex differences in endothelial glycocalyx thickness and the response to glycocalyx-targeted therapy among older adults. Physiological reports, 13(12), e70428.
  32. Alfa R, Considine T, Virani S, Pfeiffer M, Donato A, Dickerson D, Shuster D, Ellis J, Rushton K, Wei H, Gibson (2024). Clinical pharmacology and tolerability of REC-994, a redox-cycling nitroxide compound, in randomized phase 1 dose-finding studies. Pharmacology research & perspectives, 12(3), e1200.
  33. Abdeahad H, Moreno DG, Bloom SI, Huang H, Lesniewski LA, Donato A (2025). Senolytic therapy increases replicative capacity by eliminating senescent endothelial cells. Experimental gerontology, 211, 112885.
  34. Machin DR, Islam MT, Malouf A, Nguyen D, Sabouri M, Boulos M, Horn AG, Schulze KM, Layec G, Lesniewski LA, Donato A (2025). Glycocalyx-targeted therapy prevents age-related muscle loss and declines in maximal exercise capacity. Aging, 17,
  35. Lim J, Kim J, Abdeahad H, Hall SA, Lesniewski LA, Donato A (2025). Late-Life Aerobic Exercise Attenuates DNA Damage and Telomere Dysfunction in Non-Atheroprone but Not in Atheroprone Aortic Regions. Aging cell, e70196.
  36. Mahoney SA, Bloom SI, Seals DR, Donato AJ, Rossman MJ, Clayton Z (2025). Mechanisms of cellular senescence-induced vascular aging: evidence of senotherapeutic strategies. The journal of cardiovascular aging, 5(2),
  37. Abdeahad H, Moreno DG, Bloom SI, Norman L, Lesniewski LA, Donato A (2025). MitoQ reduces senescence burden in doxorubicin-treated endothelial cells by reducing mitochondrial ROS and DNA damage. American journal of physiology. Heart and circulatory physiology, 329(5), H1154-H1161.

Review

  1. Bloom SI, Islam MT, Lesniewski LA, Donato A (2023). Mechanisms and consequences of endothelial cell senescence. Nature reviews. Cardiology, 20(1), 38-51.
  2. Machin DR, Sabouri M, Zheng X, Donato A (2023). Therapeutic strategies targeting the endothelial glycocalyx. Current opinion in clinical nutrition and metabolic care, 26(6), 543-550.

Other

  1. Yuen LH, Dana S, Liu Y, Bloom SI, Thorsell AG, Neri D, Donato AJ, Kireev D, Schüler H, Franzini R (2021). Correction to "A Focused DNA-Encoded Chemical Library for the Discovery of Inhibitors of NAD(+)-Dependent Enzymes". Journal of the American Chemical Society, 143(29), 11272-11273.