The developed world is currently facing a significant increase in average lifespan, with the implication of increased age-related diseases including various cancers, dementia, type 2 diabetes, cataracts and osteoporosis in our aged population. Thus, understanding the mechanisms and pathways underlying lifespan regulation is crucial for improving health over this extended life.
Aging is characterized by increased adiposity and insulin resistance which may play a role in regulating lifespan (Huffman & Barzilai, 2009; Selman & Withers, 2011). Methionine restriction (MR) (from 0.86% to 0.172% of total diet) has been shown to decrease body weight, adiposity and improve glucose tolerance in rodents. We recently demonstrated that MR feeding in aged rodents (over 12 months old) can completely reverse age-induced increase in adiposity and metabolic dysfunction (Lees et al, 2014). Similarly to caloric restriction, MR extends lifespan but is accompanied by increased food intake and energy expenditure. However, whether these effects occur with the restriction of any essential amino acid (EAA) or are specific to methionine remains unknown.
The aim of this project is to investigate the effects of EAA restriction on age-related cognitive and motor impairments. We will assess whether deficits can be prevented or reversed with dietary interventions such as MR restrictions. We will examine the effects of EAA restriction in old, middle-aged and young mice, with specific emphasis on effects of ageing on hippocampal function and neurogenesis. We will perform blood and brain region specific lipidomics and metabolomics analysis, in collaboration with the University of St Andrews, which will then be validated in primary neuronal cultures.
The successful candidate would obtain excellent training in: in-vivo physiological assessment (PET-CT, MRI, glucose and lipid metabolism assessment), Phenotyper, Rotarod, Barnes maze test, microscopy (live cell imaging), in-vitro biochemical and molecular assays (isolation of primary cells, western blotting, ELISA, protein arrays), lipidomics, metabolomics and molecular biology techniques (microarrays, qPCR).
- Huffman DM, Barzilai N (2009) Role of visceral adipose tissue in aging. Elsevier 1790, 1117-1123.
- Selman C, Withers DJ (2011) Mammalian models of extended healthy lifespan. The Royal Society 366, 99-107.
- Lees EK, Król E, Grant L, Shearer K, Wyse C, Moncur E, Bykowska AS, Mody N, Gettys TW, Delibegovic M. (2014) Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21.Aging Cell. 13(5):817-27