Adam B. Salmon, PhD
Dr. Adam Salmon’s lab is focused on understanding the basic biology of aging by using targeted interventions to delay the aging process in mammals. Specifically, understanding how the inhibition of the mTOR signaling pathway can be used to delay aging and improve health.
We use both rodents and non-human primates as model systems to address these questions. Some key questions that we address are 1) does mTOR inhibition have similar effects in both model systems, 2) can diet interact with the pro-longevity effects of mTOR inhibition, 3) could multi-drug treatments be used to promote longevity and reduce potential side-effects.
Another focus is determining whether modulation of oxidative stress could regulate healthy lifespan; i.e., does a reduction of oxidative stress slow the development of age-related disease?
In particular, we are interested in studying the role of oxidative stress and protein oxidation in the development of metabolic dysfunction with age and obesity.
The oxidative stress theory of aging has been one of the most prominent theories of why organisms age. Both aging and increased fat accumulation promote dysregulation of glucose metabolism, alterations in adipose tissue homeostasis, and declines in cellular function that are detrimental to overall health. Metabolic diseases like Type 2 diabetes currently affect a significant proportion of the world’s population and their prevention could certainly lead to longer, healthier lives.
|1997||BS||Biological Sciences||University of Nebraska
Lincoln , NE
|2000||MS||Biological Sciences||University of Nebraska
Lincoln , NE
|2007||PhD||Cellular and Molecular Biology||University of Michigan
Ann Arbor , MI
|2011||Postdoctoral Training||Physiology of Oxidative Stress||University of Texas Health Science Center at San Antonio
San Antonio , TX
My lab’s overarching interest is focused on delineating the fundamental mechanisms of the biology of aging to develop strategies to delay the aging process including the functional declines that lead to age-related disease, frailty and death. Aging is a biological process and interventions that slow or delay aging have the benefit of also preventing, or reversing, age-related diseases and pathology like cancer, neurodegeneration, diabetes and others. The lab’s long-term goal is to translate transformative geroscience approaches discovered in basic biology towards clinical application to improve the health of aging populations.
Interventions to improve longevity and healthspan. The lab uses genetic, pharmaceutical and dietary interventions in mammalian models to better understand how longevity can be modulated and identify potential ways to move towards clinical translation. The lab is interested in better understanding how inhibition of mTOR (mechanistic target of rapamycin) is capable of extending mammalian lifespan. The mTOR signaling pathway has been shown to have a central regulatory role in aging and age-related disease through genetic or pharmaceutical (rapamycin) intervention. We are interested in expanding these findings to better understand the interplay between diet and drug interventions. In addition, we use pre-clinical non-human primate models to test the effects of rapamycin on longevity in species closely related to humans. A second significant interest is in understanding how dietary factors modulate mitochondrial function and oxidative stress during the aging process as a means to better understand pro-longevity diet interventions.
Resilience in aging. How the body responds to challenging stimuli is likely directly related to resistance to disease, pathology and potential aging. Defining such “resilience” could then have significant impact on understanding the complex phenotypes of aging. We use a novel cell-based resilience model as a potential predictive marker of aging (longevity and disease) in mammalian models. We envision the development of cellular resilience models as beneficial for personalized medicine targeted to aging and age-related disease.
Novel models of aging. Evolution has generated a world of aging models with the difference between the shortest- and longest-lived mammalian species being an order of magnitude. Probing the biology dictating such differences will help us better understand how aging is regulated. Moreover, continued development and refinement of animal and cell models has the potential to better replicate particular phenotypes of human aging.
Techniques: Animal and cellular physiology, mitochondrial and organismal metabolism
Awards & Accomplishments
|Funding Agency:||Department of Veteran's Affairs|
|Title:||"mTOR-Mediated Desaturation of Fatty Acids in Hepatic Insulin Resistance"|
|Grant Detail:||The goal of this project is to determine the interaction and effect of mTOR on lipid metabolism and its effects on insulin resistance in the liver.|
|Title:||“Characterization of marmosets as a geroscience model by the San Antonio MAP”|
|Role:||MPI: Ross and Salmon|
|Grant Detail:||The goal of this project is to facilitate the characterization of the marmoset as a laboratory animal for research on aging and age-related diseases by leveraging the expertise and resources of the San Antonio Marmoset Aging Program (SA MAP).|
|Title:||"Nathan Shock Center of Excellence in Basic Biology of Aging"|
|Role:||MPI: Strong, Hornsby, Salmon|
|Grant Detail:||The Shock Center provides Cores to support NIA funded research grants at UTHCSA. The Aging Animal and Longevity Assessment Core breeds and “ages” thousands of mice, rats and non-human primates each year and provides investigators with lifespan data and measurements of age-sensitive traits, including body composition, food consumption, and blood collection for hormone measurement.|
|Title:||"San Antonio Claude D. Pepper Older Americans Independence Center – Pre-Clinical Core"|
|Role:||MPI: Musi, Espinoza|
|Grant Detail:||The overall objective of the San Antonio OAIC is to advance aging- and metabolism-related discoveries obtained in rodents into the pre-clinical arena using non-human primates, and from the pre-clinical arena into humans through clinical studies.|
|Title:||"Feasibility of a novel nonhuman primate model of age-related nonalcoholic fatty liver disease"|
|Role:||MPI: Kamat and Salmon|
|Grant Detail:||The goal of this proposal is to test the extent to which aging drives fatty liver diseases in the marmoset and the extent to which inhibition of mTOR with rapamycin may slow this progression.|
|Title:||"Primary fibroblast resiliency as a predictor of health and lifespan in mice"|
|Grant Detail:||The goal of this proposal is to standardize tests of cellular resiliency using a skin-derived fibroblast model as a means to delineate the relationship between resiliency and mechanisms that regulate the aging process.|
|Title:||"The Role of mTOR Inhibition On Longevity And Healthy Aging In A Non-Human Primate"|
|Grant Detail:||Inhibition of the mTOR signaling pathway has been shown to extend both lifespan and healthspan in mice, but the implications of these findings for improving normal, healthy aging in humans is largely unknown. To bridge this knowledge gap, we propose testing whether mTOR inhibition by means of chronic administration of rapamycin delays aging in a non-human primate, the common marmoset, as an important step towards translational approaches to delay age-related disease in humans.|
|Period:||08/15/2014 – 04/30/2024|
|Title:||"Center for Testing Potential Anti-Aging Interventions (NIA-Aging Interventions Testing Center)"|
|Grant Detail:||This is one of three national centers funded by the National Institute on Aging whose purpose is to test interventions for which therapeutic targets have been identified that have been shown to modulate the aging process.|
|1.||Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., Javors, M. A., Lopez-Cruzan, M., Macchiarini, F., Nelson, J. F., Bitto, A., Sindler, A. L., Cortopassi, G., Kavanagh, K., Leng, L., Bucala, R., Rosenthal, N., Salmon, A., Stearns, T. M., ... Miller, R. A. (2021). 17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), [e13328]. https://doi.org/10.1111/acel.13328|
|2.||Adekunbi, D. A., Li, C., Nathanielsz, P. W., & Salmon, A. B. (2021). Age and sex modify cellular proliferation responses to oxidative stress and glucocorticoid challenges in baboon cells. GeroScience, 43(4), 2067-2085. https://doi.org/10.1007/s11357-021-00395-1|
|3.||Dorigatti, J. D., Thyne, K. M., Ginsburg, B. C., & Salmon, A. B. (2021). Beta-guanidinopropionic acid does not extend Drosophila lifespan. Biochemistry and Biophysics Reports, 27, . https://doi.org/10.1016/j.bbrep.2021.101040|
|4.||Dorigatti, J. D., Thyne, K. M., Ginsburg, B. C., & Salmon, A. B. (2021). Beta-guanidinopropionic acid has age-specific effects on markers of health and function in mice. GeroScience, 43(3), 1497-1511. https://doi.org/10.1007/s11357-021-00372-8|
|5.||Lee, H. J., Donati, A., Feliers, D., Sun, Y., Ding, Y., Madesh, M., Salmon, A. B., Ikeno, Y., Ross, C., O'Connor, C. L., Ju, W., Bitzer, M., Chen, Y., Choudhury, G. G., Singh, B. B., Sharma, K., & Kasinath, B. S. (2021). Chloride channel accessory 1 integrates chloride channel activity and mTORC1 in aging-related kidney injury. Aging cell, 20(7), [e13407]. https://doi.org/10.1111/acel.13407|
|6.||Horvath, S., Zoller, J. A., Haghani, A., Lu, A. T., Raj, K., Jasinska, A. J., Mattison, J. A., & Salmon, A. B. (2021). DNA methylation age analysis of rapamycin in common marmosets. GeroScience, 43(5), 2413-2425. https://doi.org/10.1007/s11357-021-00438-7|
|7.||Adekunbi, D. A., Nathanielsz, P. W., & Salmon, A. B. (2021). Editorial Cellular resilience and baboon aging. Aging, 13(22), 24482-24484. https://doi.org/10.18632/aging.203728|
|8.||Lindquist, K. A., Belugin, S., Hovhannisyan, A. H., Corey, T. M., Salmon, A., & Akopian, A. N. (2021). Identification of trigeminal sensory neuronal types innervating masseter muscle. eNeuro, 8(5), [ENEURO.0176-21.2021]. https://doi.org/10.1523/ENEURO.0176-21.2021|
|9.||Dorigatti, A. O., Hussong, S. A., Hernandez, S. F., Sills, A. M., Salmon, A. B., & Galvan, V. (2021). Primary neuron and astrocyte cultures from postnatal Callithrix jacchus: a non-human primate in vitro model for research in neuroscience, nervous system aging, and neurological diseases of aging. GeroScience, 43(1), 115-124. https://doi.org/10.1007/s11357-020-00284-z|
|10.||Salmon, A. B., Nelson, J. F., Gelfond, J. A. L., Javors, M., Ginsburg, B., Lopez-Cruzan, M., Galvan, V., Fernandez, E., Musi, N., Ikeno, Y., Hubbard, G., Lechleiter, J., Hornsby, P. J., & Strong, R. (2021). San Antonio Nathan Shock Center: your one-stop shop for aging research. GeroScience, 43(5), 2105-2118. https://doi.org/10.1007/s11357-021-00417-y|
|11.||Buffenstein, R., Amoroso, V., Andziak, B., Avdieiev, S., Azpurua, J., Barker, A. J., Bennett, N. C., Brieño-Enríquez, M. A., Bronner, G. N., Coen, C., Delaney, M. A., Dengler-Crish, C. M., Edrey, Y. H., Faulkes, C. G., Frankel, D., Friedlander, G., Gibney, P. A., Gorbunova, V., Hine, C., ... Smith, E. S. J. (Accepted/In press). The naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole-rat biology. Biological Reviews, 97(1), 115-140. https://doi.org/10.1111/brv.12791|
|12.||Miller, R. A., Harrison, D. E., Allison, D. B., Bogue, M., Debarba, L., Diaz, V., Fernandez, E., Galecki, A., Timothy Garvey, W., Jayarathne, H., Kumar, N., Javors, M. A., Ladiges, W. C., Macchiarini, F., Nelson, J., Reifsnyder, P., Rosenthal, N. A., Sadagurski, M., Salmon, A. B., ... Strong, R. (2020). Canagliflozin extends life span in genetically heterogeneous male but not female mice. JCI Insight, 5(21), [e140019]. https://doi.org/10.1172/jci.insight.140019|
|13.||Strong, R., Miller, R. A., Bogue, M., Fernandez, E., Javors, M. A., Libert, S., Marinez, P. A., Murphy, M. P., Musi, N., Nelson, J. F., Petrascheck, M., Reifsnyder, P., Richardson, A., Salmon, A. B., Macchiarini, F., & Harrison, D. E. (2020). Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects. Aging cell, 19(11), [e13269]. https://doi.org/10.1111/acel.13269|
|14.||Sills, A. M., Artavia, J. M., DeRosa, B. D., Ross, C. N., & Salmon, A. B. (2019). Long-term treatment with the mTOR inhibitor rapamycin has minor effect on clinical laboratory markers in middle-aged marmosets. American Journal of Primatology, 81(2), [e22927]. https://doi.org/10.1002/ajp.22927|
|15.||Lee, H. J., Feliers, D., Barnes, J. L., Oh, S., Choudhury, G. G., Diaz, V., Galvan, V., Strong, R., Nelson, J., Salmon, A., Kevil, C. G., & Kasinath, B. S. (2018). Hydrogen sulfide ameliorates aging-associated changes in the kidney. GeroScience, 40(2), 163-176. https://doi.org/10.1007/s11357-018-0018-y|
|16.||Salmon, A. B., Dorigatti, J., Huber, H. F., Li, C., & Nathanielsz, P. W. (2018). Maternal nutrient restriction in baboon programs later-life cellular growth and respiration of cultured skin fibroblasts: a potential model for the study of aging-programming interactions. GeroScience, 40(3), 269-278. https://doi.org/10.1007/s11357-018-0024-0|
|17.||Weiss, R., Fernandez, E., Liu, Y., Strong, R., & Salmon, A. B. (2018). Metformin reduces glucose intolerance caused by rapamycin treatment in genetically heterogeneous female mice. Aging, 10(3), 386-401. https://doi.org/10.18632/aging.101401|
|18.||Zhou, J., Chong, S. Y., Lim, A., Singh, B. K., Sinha, R. A., Salmon, A. B., & Yen, P. M. (2017). Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging. Aging, 9(2), 583-599. https://doi.org/10.18632/aging.101181|
|19.||Salmon, A. B., Kim, G., Liu, C., Wren, J. D., Georgescu, C., Richardson, A., & Levine, R. L. (2016). Effects of transgenic methionine sulfoxide reductase A (MsrA) expression on lifespan and age-dependent changes in metabolic function in mice. Redox Biology, 10, 251-256. https://doi.org/10.1016/j.redox.2016.10.012|
|20.||Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., Fernandez, E., Flurkey, K., Hamilton, K. L., Lamming, D. W., Javors, M. A., de Magalhães, J. P., Martinez, P. A., McCord, J. M., Miller, B. F., Müller, M., Nelson, J. F., Ndukum, J., Rainger, G. E., ... Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging cell, 15(5), 872-884. https://doi.org/10.1111/acel.12496|
|21.||Lelegren, M., Liu, Y., Ross, C., Tardif, S., & Salmon, A. B. (2016). Pharmaceutical inhibition of mTOR in the common marmoset: Effect of rapamycin on regulators of proteostasis in a non-human primate. Pathobiology of Aging and Age-related Diseases, 6, . https://doi.org/10.3402/pba.v6.31793|