Main Research Lines:
- Development of metabolic interventions for successful aging
- Development of synthetic thyroid hormones for metabolic diseases
Main Research Lines:
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.
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Instituto de Salud Carlos IIII: PIS2018-001590. Evaluation of acetyl coenzyme A restriction as a geroprotector therapy to promote healthy aging.
For a complete list of publications see (https:/www.ncbi.nlm.nih.gov/pubmed/?term=martin-montalvo+a).