Aging and Neurodegeneration
The purpose of research will be to study the Sirtuin 1 / AMPK / mTOR pathways in mouse models of senescence and Alzheimer’s disease (AD), and to establish their participation in the mitochondrial dysfunction that leads to frailty and hence to pathological brain aging. Briefly, genetic and environmental causes can modulate brain aging directly or through changes of body homeostasis. A number of life style interventions can induce neuroprotection against AD through boosting of mitochondrial functionality and induction of neurotrophic factors. Longevity and neuroprotective genes such as Sirtuins are likely involved. To rescue frail mitochondria and to protect the development of AD triggered by age-related mechanisms we will modulate the Sirtuin 1 / AMPK / mTOR network using pharmacological treatments (melatonin, resveratrol and specific agents) and genetic tools that induce changes in Sirtuin 1 expression.
The research will be developed by using the following techniques:
- Engineering of viral vectors and other molecular techniques
- Behavioral studies in mice
- In vitro testing in cell cultures
- Biochemistry and microscopy
- Post-mortem human tissue studies
The research program is a continuation of work published in J Alzheimers Dis. 2010;20(1):229-45, which provided demonstration of the increased vulnerability to amyloid pathology of brain cells in an aged-mimicked environment. Next, we demonstrated that physical exercise and melatonin boosted defences against AD pathology and cognitive lost in 3xTg-AD mice, as published in J Alzheimers Dis. 2011;24(3):421-54 and Neurobiol Aging. 2011 Dec 16. [Epub ahead of print]. Also, melatonin and resveratrol enhanced sirtuin 1 expression and protected against frailty in senescent neurons cultured from SAMP8, see J Pineal Res. 2012 Apr;52(3):271-81.
The host research group is committed to the study of aging and neurodegeneration for several years and had gained expertise in the subject. The team regularly collaborates with main age-related research groups in Spain, firstly through a RETICS network and at present through a Consolider net. The long-term goal is to define and protect from the causes through which normal aging turns into neurodegenerative processes such as Azheimer’s disease.
Brain, aging, Alzheimer’s disease, neuroprotection, sirtuins, healthy lifestyles
The candidate should have knowledge in neuron and astrocyte functionality, age-related processes and/or pathological brain processes (AD), allowing directing his/her own research to obtain appropriate milestones along the research program.
It is expected a thorough background on molecular and cellular biology techniques, that lead to relevant findings in gene regulation and molecular mechanisms of pathological brain aging. Additional skills in in vivo studies are desirable, provided that a multidisciplinary research should be performed to advance to the proposed goals.
The candidate will work as a part of a research team and should be able to direct junior members of the laboratory, but also to work independently and to use own initiative when required.
Team strategic objective in IDIBAPS
Furthering of knowledge of the physiopathological mechanisms of neurological and psychiatric diseases and neurotoxic and aging processes of the central nervous system, with a view to identifying new cellular and functional targets and proposing new treatments.(Read eligibility criteria)