Title:Experimental Models for Aging and their Potential for Novel Drug Discovery
Volume: 16
Issue: 10
Author(s): Jaume Folch, Oriol Busquets, Miren Ettcheto, Elena Sánchez-López, Mercè Pallàs, Carlos Beas-Zarate, Miguel Marin, Gemma Casadesus, Jordi Olloquequi, Carme Auladell and Antoni Camins*
Affiliation:
- Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid,Spain
Keywords:
Aging, Resveratrol, sirtuins, IGF-1, mTOR, heterogeneous mice model, SAMP8.
Abstract: Background: An interesting area of scientific research is the development of potential
antiaging drugs. In order to pursue this goal, it is necessary to gather the specific knowledge about
the adequate preclinical models that are available to evaluate the beneficial effects of new potential
drugs. This review is focused on invertebrate and vertebrate preclinical models used to evaluate the
efficacy of antiaging compounds, with the objective to extend life span and health span.
Methods: Research and online content related to aging, antiaging drugs, experimental aging models
is reviewed. Moreover, in this review, the main experimental preclinical models of organisms that
have contributed to the research in the pharmacology of lifespan extension and the understanding of
the aging process are discussed.
Results: Dietary restriction (DR) constitutes a common experimental process to extend life span in
all organisms. Besides, classical antiaging drugs such as resveratrol, rapamycin and metformin
denominated as DR mimetics are also discussed. Likewise, the main therapeutic targets of these
drugs include sirtuins, IGF-1, and mTOR, all of them being modulated by DR.
Conclusion: Advances in molecular biology have uncovered the potential molecular pathways
involved in the aging process. Due to their characteristics, invertebrate models are mainly used
for drug screening. The National Institute on Aging (NIA) developed the Interventions Testing Program
(ITP). At the preclinical level, the ITP uses Heterogeneous mouse model (HET) which is
probably the most suitable rodent model to study potential drugs against aging prevention. The
accelerated-senescence mouse P8 is also a mammalian rodent model for aging research. However,
when evaluating the effect of drugs on a preclinical level, the evaluation must be done in
non-human primates since it is the mammalian specie closest to humans. Research is needed to
investigate the impact of new potential drugs for the increase of human quality of life.
