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 tested.
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. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16.
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.
17. 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.
18.
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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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
26. 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.
Dr. Isabel Espadas Villanueva- Dr. Raúl López Férnandez
- María de los Ángeles Cáliz Molina
- María Camacho Cabrera
- Inmaculada Pino Pérez
- Ryan Conesa Bakkali
- Jose Enrique Oranto Bosch
- María Rivero Lobo
- Francisca María Díaz Rodríguez
