Centro Andaluz de Biología Molecular y Medicina Regenerativa
Alejandro Martín-Montalvo Sánchez

Email: alejandro.martinmontalvo@cabimer.es

 

Main Research Lines:

  1. Development of metabolic interventions for successful aging
  1. Development of synthetic thyroid hormones for metabolic diseases

In our current society, more than 50% of elderly humans suffer age-related disabilities that impede optimal quality of life and reduce life expectancy. These disabilities imply important suffering for aging individuals and their families. Currently, the prevalence of age-related metabolic disorders and physical impediments is high and more worryingly, the incidence of this pleiotropic type of diseases/disabilities is rising in parallel. Given the high incidence of metabolic pathologies, research investigating the onset of chronic age-related metabolic complications is of great importance in the understanding of aging processes. Interventions that delay, or even revert, metabolic disorders could protect other age-related diseases, since epidemiological data indicates that patients suffering metabolic complications have higher likelihood to develop the vast majority of age-related diseases such as cancer, cardiovascular disease and neurodegenerative diseases, later in life. Therefore, there is an urgent need to develop more effective strategies to prevent and treat age-related diseases/disabilities. Our research goal is to identify novel therapeutically promising strategies able to improve the quality of life and life expectancy in humans.

The use of geroprotectors for healthy aging

We are currently investigating novel approaches to modulate metabolism and aging by targeting the restriction of nuclear/cytosolic Acetyl Coenzyme A (Ac-CoA) levels in mammals. We are evaluating whether a chronic reduction on cytosolic/nuclear Ac-CoA levels using cytosolic Ac-CoA reducing agents, prevent and/or revert metabolic complications, and extend healthspan and lifespan in mammals. In brief, our research includes the determination of the maximal inhibition of the specific proteins promoted by Anti Aging Agents (AAAs) that sustains optimal function in murine primary cells. The in vivo characterization of the metabolic homeostasis and xenobiotic-induced stress resistance in mice treated with AAAs. Subsequently, we determine of the effects of chronic treatment with AAAs on the health and longevity in mice and the mechanism of action of AAAs in the main metabolic tissues of mice. If results are supportive, we initiate the translation of our basic research by evaluating the efficacy of AAAs in pilot human clinical trials.

Novel thyromimetics in metabolic diseases

The current therapy for the treatment of type 1 diabetes mellitus is the chronic administration of insulin, a palliative treatment that is not directed to the root cause of the disease. We have shown that the natural thyroid hormones improve glucose tolerance, blunt the onset and increase survival in two experimental models of Type 1 diabetes mellitus. Unfortunately, long-term treatments with natural thyroid hormones cause toxicity and premature death. We are currently developing synthetic thyroid hormones to direct thyroid hormones to the pancreatic β-cells to determine if treatments for metabolic diseases could be developed using this strategy, while avoiding the long-term side effects of natural thyroid hormones.

ResearcherID: C-2031-2017
Scopus: 25635883500
ORCID: 
0000-0002-3886-5355

Current funding:

Instituto de Salud Carlos IIII: PIS2018-001590. Evaluation of acetyl coenzyme A restriction as a geroprotector therapy to promote healthy aging.

Recent publications:

For a complete list of publications see (https://www.ncbi.nlm.nih.gov/pubmed/?term=martin-montalvo+a).

  1. Bakula D, Aliper AM, Mamoshina P, Petr MA, Teklu A, Baur JA, Campisi J, Ewald CY, Georgiev skaya A, Gladyshev VN, Kovalchuk O, Lamming DW, Luijsterburg MS, Martín-Montalvo A, Maudsley S, Mkrtchyan GV, Moskalev A, Olshansky SJ, Ozerov IV, Pickett A, Ristow M, Zhavoronkov A, Scheibye-Knudsen M. Aging and drug discovery. Aging (Albany NY). 2018. doi: 10.18632/aging.101646.
  1. Martin-Montalvo A, López-Noriega L, Jiménez-Moreno C, Herranz A, Lorenzo PI, Cobo-Vuilleumier N, Tamayo A, González-Guerrero C, Hofsteede JSWR, Lebreton F, Bosco D, García Toscano M, Herranz L, Anselmo J, Moreno JC, Gauthier BR. Transient PAX8Expression in Islets During Pregnancy Correlates With β-Cell Survival, Revealing a Novel Candidate Gene in Gestational Diabetes Mellitus. Diabetes. 2019. doi: 10.2337/db18-0285.
  1. González-Mariscal I, Martin-Montalvo A, Vazquez-Fonseca L, Pomares-Viciana T, Sánchez-Cuesta A, Fernández-Ayala DJ, Navas P, Santos-Ocana C. The mitochondrial phosphatase PPTC7 orchestrates mitochondrial metabolism regulating coenzyme Q10biosynthesis. Biochim Biophys Acta Bioenerg. 2018. doi: 10.1016/j.bbabio.2018.09.369.
  1. Diaz-Ruiz A, Lanasa M, Garcia J, Mora H, Fan F, Martin-Montalvo A, Di Francesco A, Calvo-Rubio M, Salvador-Pascual A, Aon MA, Fishbein KW, Pearson KJ, Villalba JM, Navas P, Bernier M, de Cabo R. Overexpression of CYB5R3 and NQO1, two NAD+-producing enzymes, mimics aspects of caloric restriction. Aging Cell. 2018. doi: 10.1111/acel.12767.
  1. Cobo-Vuilleumier N, Lorenzo PI, Rodríguez NG, Herrera Gómez IG, Fuente-Martin E, López-Noriega L, Mellado-Gil JM, Romero-Zerbo SY, Baquié M, Lachaud CC, Stifter K, Perdomo G, Bugliani M, De Tata V, Bosco D, Parnaud G, Pozo D, Hmadcha A, Florido JP, Toscano MG, de Haan P, Schoonjans K, Sánchez Palazón L, Marchetti P, Schirmbeck R, Martín-Montalvo A, Meda P, Soria B, Bermúdez-Silva FJ, St-Onge L, Gauthier BR. LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus. Nat Commun. 2018. doi: 10.1038/s41467-018-03943-0.
  1. Mellado-Gil JM, Fuente-Martín E, Lorenzo PI, Cobo-Vuilleumier N, López-Noriega L, Martín-Montalvo A, Gómez IGH, Ceballos-Chávez M, Gómez-Jaramillo L, Campos-Caro A, Romero-Zerbo SY, Rodríguez-Comas J, Servitja JM, Rojo-Martinez G, Hmadcha A, Soria B, Bugliani M, Marchetti P, Bérmudez-Silva FJ, Reyes JC, Aguilar-Diosdado M, Gauthier BR. The type 2 diabetes-associated HMG20A gene is mandatory for islet beta cell functional maturity. Cell Death Dis. 2018. doi: 10.1038/s41419-018-0272-z.
  1. López-Noriega L, Cobo-Vuilleumier N, Narbona-Pérez ÁJ, Araujo-Garrido JL, Lorenzo PI, Mellado-Gil JM, Moreno JC, Gauthier BR, Martín-Montalvo A. Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice. Br J Pharmacol. 2017. doi: 10.1111/bph.13975.
  1. Mercken EM, Capri M, Carboneau BA, Conte M, Heidler J, Santoro A, Martin-Montalvo A, Gonzalez-Freire M, Khraiwesh H, González-Reyes JA, Moaddel R, Zhang Y, Becker KG, Villalba JM, Mattison JA, Wittig I, Franceschi C, de Cabo R. Conserved and species-specific molecular denominators in mammalian skeletal muscle aging. NPJ Aging Mech Dis. 2017 doi: 10.1038/s41514-017-0009-8.
  1. González-Mariscal I, Martín-Montalvo A, Ojeda-González C, Rodríguez-Eguren A, Gutiérrez-Ríos P, Navas P, Santos-Ocaña C. Balanced CoQ6biosynthesis is required for lifespan and mitophagy in yeast. Microb Cell. 2017. doi: 10.15698/mic2017.02.556.
  1. Martin-Montalvo A, Lorenzo PI, López-Noriega L, Gauthier BR. Targeting pancreatic expressed PAX genes for the treatment of diabetes mellitus and pancreatic neuroendocrine tumors. Expert Opin Ther Targets. 2017, Doi:10.1080/14728222.2017.1257000.
  1. Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, Cacciottolo M, Martin-Montalvo A, de Cabo R, Wei M, Morgan TE, Longo VD. Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity. Cancer Cell. 2016. doi: 10.1016/j.ccell.2016.06.005.
  1. Martin-Montalvo A, Sun Y, Diaz-Ruiz A, Ali A, Gutierrez V, Palacios HH, Curtis J, Siendones E, Ariza J, Abulwerdi GA, Sun X, Wang AX, Pearson KJ, Fishbein KW, Spencer RG, Wang M, Han X, Scheibye-Knudsen M, Baur JA, Shertzer HG, Navas P, Villalba JM, Zou S, Bernier M, de Cabo R. Cytochrome b5 reductase and the control of lipid metabolism and healthspan. NPJ Aging Mech Dis. 2016. doi: 10.1038/npjamd.2016.6.
  1. Noren Hooten N, Martin-Montalvo A, Dluzen DF, Zhang Y, Bernier M, Zonderman AB, Becker KG, Gorospe M, de Cabo R, Evans MK. Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence. Aging Cell. 2016 doi: 10.1111/acel.12469.
  1. Mellado-Gil JM, Jiménez-Moreno CM, Martin-Montalvo A, Alvarez-Mercado AI, Fuente-Martin E, Cobo-Vuilleumier N, Lorenzo PI, Bru-Tari E, Herrera-Gómez Ide G, López-Noriega L, Pérez-Florido J, Santoyo-López J, Spyrantis A, Meda P, Boehm BO, Quesada I, Gauthier BR. PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus. Diabetologia. 2016. doi: 10.1007/s00125-016-3864-0.
  1. Lorenzo PI, Fuente-Martín E, Brun T, Cobo-Vuilleumier N, Jimenez-Moreno CM, G Herrera Gomez I, López Noriega L, Mellado-Gil JM, Martin-Montalvo A, Soria B, Gauthier BR. PAX4 Defines an Expandable β-Cell Subpopulation in the Adult Pancreatic Islet. Sci Rep. 2015. doi: 10.1038/srep15672.
  1. Jimenez-Moreno CM, Herrera-Gomez IG, Lopez-Noriega L, Lorenzo PI, Cobo-Vuilleumier N, Fuente-Martin E, Mellado-Gil JM, Parnaud G, Bosco D, Gauthier BR, Martin-Montalvo A. A Simple High Efficiency Intra-Islet Transduction Protocol Using Lentiviral Vectors. Curr Gene Ther. 2015;15(4):436-46. Doi:10.2174/1566523215666150630121557
  1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015. doi: 10.1016/j.cmet.2015.02.009.