Centro Andaluz de Biología Molecular y Medicina Regenerativa

Development of metabolic interventions

/Research Groups/Development of metabolic interventions

Main Research Line:

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. 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.

We are currently investigating novel approaches to modulate metabolism and aging by two main molecular mechanisms. We are 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, we are investigating the regenerative potential of ATP-citrate lyase inhibitors in tissue regeneration. Another line of research is evaluating the potential of the potentiation of sulfur metabolism on aging and age-related diseases. We are investigating different aspects of aging such as tissue regeneration, metabolic health, locomotor function, cancer and neurocognitive diseases.

Our research involves the use of laboratory mice using different experimental approaches ranging from acute treatments (single exposure to the intervention) to longevity assays in mice (3 year intervention). We determine alterations in different parameters of health during the different phases of life in mice. We also use the latest approaches to define the molecular mechanisms altered in aging and alterations produced by experimental treatments


Immunohistochemistry in brain


Immunocytochemistry in neuronal cultures.

 

Join us!

If you want to apply to our lab as a Master Student, PhD Students or Postdoc, send a motivation letter, CV and contact details to alejandro.martinmontalvo@cabimer.es

ResearcherID: C-2031-2017
Scopus: 25635883500

ORCID: 0000-0002-3886-5355

Current funding:

CSIC. La modulación de la oxidación de cisteínas como mecanismo relevante en la salud y el envejecimiento. Code: 202220I059

Ministry of Health and Innovation. El aumento en la S-sufihidración de cisteínas promovida por generadores intracelulares del sulfuro de hidrógeno como estrategia para conseguir un envejecimiento más saludable. Code: PID2021-123965OB-I00

Recent publications:

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

1. Cobo-Vuilleumier N, Rodríguez-Fernandez S, López-Noriega L, Lorenzo PI, Franco JM, Lachaud CC, Vazquez EM, Legido RA, Dorronsoro A, López-Férnandez-Sobrino R, Fernández-Santos B, Serrano CE, Salas-Lloret D, van Overbeek N, Ramos-Rodriguez M, Mateo-Rodríguez C, Hidalgo L, Marin-Canas S, Nano R, Arroba AI, Caro AC, Vertegaal AC, Montalvo AM, Martín F, Aguilar-Diosdado M, Piemonti L, Pasquali L, Prieto RG, Sánchez MIG, Eizirik DL, Martínez-Brocca MA, Vives-Pi M, Gauthier BR. LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype. Clin Transl Med. 2024 Dec;14(12):e70134. doi: 10.1002/ctm2.70134.PMID: 39702941

2. Lluch A, Latorre J, Oliveras-Cañellas N, Fernández-Sánchez A, Moreno-Navarrete JM, Castells-Nobau A, Comas F, Buxò M, Rodríguez-Hermosa JI, Ballester M, Espadas I, Martín-Montalvo A, Zhang B, Zhou Y, Burkhardt R, Höring M, Liebisch G, Castellanos-Rubio A, Santin I, Kar A, Laakso M, Pajukanta P, Olkkonen VM, Fernández-Real JM, Ortega FJ. A novel long non-coding RNA connects obesity to impaired adipocyte function. Mol Metab. 2024 Dec;90:102040. doi: 10.1016/j.molmet.2024.102040. Epub 2024 Oct 1.PMID: 39362599

3. Espadas I, Cáliz-Molina MÁ, López-Fernández-Sobrino R, Panadero-Morón C, Sola-García A, Soriano-Navarro M, Martínez-Force E, Venegas-Calerón M, Salas JJ, Martín F, Gauthier BR, Alfaro-Cervelló C, Martí-Aguado D, Capilla-González V, Martín-Montalvo A. Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status. Aging Cell. 2024 Sep;23(9):e14205. doi: 10.1111/acel.14205. Epub 2024 May 17.PMID: 38760909 Free PMC article.

4. Hine C, Ponti AK, Cáliz-Molina MÁ, Martín-Montalvo A. H2S serves as the immunoregulatory essence of apoptotic cell death. Cell Metab. 2024 Jan 2;36(1):3-5. doi: 10.1016/j.cmet.2023.12.006.

5. Lluch A, Latorre J, Serena-Maione A, Espadas I, Caballano-Infantes E, Moreno-Navarrete JM, Oliveras-Cañellas N, Ricart W, Malagón MM, Martin-Montalvo A, Birchmeier W, Szymanski W, Graumann J, Gómez-Serrano M, Sommariva E, Fernández-Real JM, Ortega FJ. Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence. Nat Commun. 2023 Aug 22;14(1):5106. doi: 10.1038/s41467-023-40596-0.

6. Sola-García A, Cáliz-Molina MÁ, Espadas I, Petr M, Panadero-Morón C, González-Morán D, Martín-Vázquez ME, Narbona-Pérez ÁJ, López-Noriega L, Martínez-Corrales G, López-Fernández-Sobrino R, Carmona-Marin LM, Martínez-Force E, Yanes O, Vinaixa M, López-López D, Reyes JC, Dopazo J, Martín F, Gauthier BR, Scheibye-Knudsen M, Capilla-González V, Martín-Montalvo A. Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging. Commun Biol. 2023 Mar 8;6(1):250. doi: 10.1038/s42003-023-04625-4.

7. Baliña-Sánchez C, Aguilera Y, Adán N, Sierra-Párraga JM, Olmedo-Moreno L, Panadero-Morón C, Cabello-Laureano R, Márquez-Vega C, Martín-Montalvo A, Capilla-González V. Generation of mesenchymal stromal cells from urine-derived iPSCs of pediatric brain tumor patients. Front Immunol. 2023 Jan 26;14:1022676. doi: 10.3389/fimmu.2023.1022676. eCollection 2023.

8. Cabré N, Luciano-Mateo F, Chapski DJ, Baiges-Gaya G, Fernández-Arroyo S, Hernández-Aguilera A, Castañé H, Rodríguez-Tomàs E, París M, Sabench F, Castillo DD, Del Bas JM, Tomé M, Bodineau C, Sola-García A, López-Miranda J, Martín-Montalvo A, Durán RV, Vondriska TM, Rosa-Garrido M, Camps J, Menéndez JA, Joven J. Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis. Int J Mol Sci. 2022 Jul 15;23(14):7830. doi: 10.3390/ijms23147830.

9. Olmedo-Moreno L, Aguilera Y, Baliña-Sánchez C, Martín-Montalvo A, Capilla-González V. Heterogeneity of In Vitro Expanded Mesenchymal Stromal Cells and Strategies to Improve Their Therapeutic Actions. Pharmaceutics. 2022 May 23;14(5):1112. doi: 10.3390/pharmaceutics14051112.

10. Martin Vázquez E, Cobo-Vuilleumier N, Araujo Legido R, Marín-Cañas S, Nola E, Dorronsoro A, López Bermudo L, Crespo A, Romero-Zerbo SY, García-Fernández M, Martin Montalvo A, Rojas A, Comaills V, Bérmudez-Silva FJ, Gannon M, Martin F, Eizirik D, Lorenzo PI, Gauthier BR. NR5A2/LRH-1 regulates the PTGS2-PGE2-PTGER1 pathway contributing to pancreatic islet survival and function. iScience. 2022 May 2;25(5):104345. doi: 10.1016/j.isci.2022.104345. eCollection 2022 May 20.

11. Lorenzo PI, Martin Vazquez E, López-Noriega L, Fuente-Martín E, Mellado-Gil JM, Franco JM, Cobo-Vuilleumier N, Guerrero Martínez JA, Romero-Zerbo SY, Perez-Cabello JA, Rivero Canalejo S, Campos-Caro A, Lachaud CC, Crespo Barreda A, Aguilar-Diosdado M, García Fuentes E, Martin-Montalvo A, Álvarez Dolado M, Martin F, Rojo-Martinez G, Pozo D, Bérmudez-Silva FJ, Comaills V, Reyes JC, Gauthier BR. The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity. Theranostics. 2021 May 12;11(14):6983-7004. doi: 10.7150/thno.57237. eCollection 2021.

12. Álvarez-Amor L, Sierra AL, Cárdenas A, López-Bermudo L, López-Beas J, Andújar E, Pérez-Alegre M, Gallego-Durán R, Varela LM, Martin-Montalvo A, Berná G, Rojas A, Robles-Frías MJ, Hmadcha A, Romero-Gómez M, Kleemann R, Martín F. Extra virgin olive oil improved body weight and insulin sensitivity in high fat diet-induced obese LDLr-/-.Leiden mice without attenuation of steatohepatitis. Sci Rep. 2021 Apr 15;11(1):8250. doi: 10.1038/s41598-021-87761-3

13. López-Noriega L, Capilla-González V, Cobo-Vuilleumier N, Martin-Vazquez E, Lorenzo PI, Martinez-Force E, Soriano-Navarro M, García-Fernández M, Romero-Zerbo SY, Bermúdez-Silva FJ, Díaz-Contreras I, Sánchez-Cuesta A, Santos-Ocaña C, Hmadcha A, Soria B, Martín F, Gauthier BR, Martin-Montalvo A. Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging. Aging (Albany NY). 2019 Sep 13;11(18):7746-7779. doi: 10.18632/aging.102285. Epub 2019 Sep 13.

14. Soria B, Martin-Montalvo A, Aguilera Y, Mellado-Damas N, López-Beas J, Herrera-Herrera I, López E, Barcia JA, Alvarez-Dolado M, Hmadcha A, Capilla-González V. Human Mesenchymal Stem Cells Prevent Neurological Complications of Radiotherapy. Front Cell Neurosci. 2019 May 16;13:204. doi: 10.3389/fncel.2019.00204. eCollection 2019.

15. McGreevy KR, Tezanos P, Ferreiro-Villar I, Pallé A, Moreno-Serrano M, Esteve-Codina A, Lamas-Toranzo I, Bermejo-Álvarez P, Fernández-Punzano J, Martín-Montalvo A, Montalbán R, Ferrón SR, Radford EJ, Fontán-Lozano Á, Trejo JL. Intergenerational transmission of the positive effects of physical exercise on brain and cognition. Proc Natl Acad Sci U S A. 2019 May 14;116(20):10103-10112. doi: 10.1073/pnas.1816781116. Epub 2019 Apr 22.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. Jimenez-Moreno CM, Herrera-Gomez IG, Lopez-Noriega L, Lorenzo PI, Cobo-Vuilleumier N, Fuente-Martin 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

29. 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.


Group leader:
Postdoctorals:
  • Dr. Almudena García Ruiz
  • Dr. Raúl López Férnandez
PhD students:
  • María Camacho Cabrera
  • Inmaculada Pino Pérez
Technicians:
  • María Rivero Lobo
Master Students / Erasmus +:
  • María del Carmen Vilches Pérez