Intro: Muscle atrophy is seen with aging. PGC-1α is a transcriiptional co-activator known as the master regulator of mitochondrial Essay

Intro: Muscle atrophy is seen with aging.
PGC-1α is a transcriiptional co-activator known as the master regulator of mitochondrial biogenesis. Its control of metabolism has been suggested to exert critical influence in the aging process. PGC1alpha was shown to rescue age-related sarcopenia.
By comparing very old mice overexpressing PGC1a in muscle with control mice, Moraes and colleagues saw an increase in young-like molecular patterns. Besides many functional effects seen in muscle genes related to autophagy and neuromuscular junctions, we saw an interesting gene, ARNTL, which is associated with muscle disease in human and ageing. ARNTL is a transcriiption factor involved in circadian regulation and its KO among other circadian dysregulations, induce premature ageing and sarcopenia. PGC1a regulates ARNTL by binding RORalpha: this induces the transcriiption of Bmal1, which in turn activates the transcriiption of the clock machinery. ARNTL is actually a pioneer-like transcriiption factor.

So our research question is something like: we know pgc1alpha rescues from age-related sarcopenia but is it bmal1 (circadian clock) dependent process? Can we restore circadian rhythm with PGC1alpha expression and does it help in age related sarcopenia?

For this experiment we will use WT young mice, WT old mice, mice model with doxycycline induced PGC1alpha overexpression, and mice model with doxycycline induced PC1alpha overexpression Arntl Knockout

Techniques; RT-PCR of PGC1alpha and BMAL and upstream genes as well as functional assays to check whether our research question is true. Please elaborate on these a bit more.

Please write a research proposal on the topic described above and use the above as a guide. It should include a 1. longer introduction, 2. methods, and materials section with descriiptions of each and why we use it, 3. relevance of the study 4. and limitations (longest part).

Thank you in advance