Background
Obesity is caused by a complex interplay of genetic, epigenetic and environmental factors. It has been shown that obesity accelerates ageing in a tissue-specific manner, as reported e.g. for human liver. Advanced DNA methylation age has been shown to be related to BMI and metabolic syndrome. Very recently, it has been shown that the lipid uptake rate is increased in older age leading to increased weight accumulation at higher age. Here, we will test for a
- potential relationship between accelerated aging and lipid uptake / storages in adipocytes and
- whether the epigenetic age in adipocytes can be slowed/reverse by NAD+ exposure.
The problem
- Is the epigenetic, biological age in adipocytes related to clinical variables?
- Do adipocytes from visceral vs. subcutaneous fat depot have a different ticking rate?
- Does accelerated aging translate into different lipid uptake/storage?
- Can these effects be slowed or reversed by NAD+ exposure?
Goal and Method
- Is the epigenetic, biological age in adipocytes related to clinical variables?
- DNA methylation levels shall be determined on a genome-wide level in adipocytes. Here, we will use array-based methods on extracted genomic DNA from adipocytes. Measurements of cell senescence markers in adipocytes and pre-adipocytes/progenitor cells shall be performed.
- Do adipocytes from visceral vs. subcutaneous fat depot have a different ticking rate?
- DNA methylation clock measurements can be used to generate a measure of DNA methylation acceleration in adipocytes from different fat depot. The epigenetic clock between the two depots shall be compared. As visceral adipose tissue is more deleterious for obese individuals than accumulating subcutaneous fat, a different ticking rate might be related to metabolic variables.
- Does accelerated aging translate into different lipid uptake/Storage?
- Lipid staining and lipid uptake assays shall be performed. It shall be tested the hypothesis that higher epigenetic (biological) age – as inferred from epigenetic clock data – correlates with lipid uptake.
- Can these effects be slowed or reversed by NAD+ exposure?
- Adipocytes shall be exposed to NAD+, which has been shown to increased life span. Here, we will test whether NAD+ treatment translates into younger epigenetic age. This will be complemented by measuring markers of senescence.
The student's tasks
The student work will include the following:
- cell culture to grow adipocytes
- generate DNA methylation data sets on extracted genomic DNA
- determine epigenetic clock data by using the DNAm PhenoAge calculator
- perform lipid staining and lipid uptake assays in adipocytes
- perform NAD+ exposure
About the research group
Our research group performs research in obesity and type 2 diabetes with a special emphasis on the genetic basis (SNP markers) and epigenetic factors (DNA methylation, RNA modification). Currently, three postdocs and a technician are working in the group that has been established in 2016. Since then we have established a large network of both clinically oriented and basic science-oriented collaborations within Norway. We are located at the Akershus University Hospital at EpiGen laboratory, where we have a strong and stimulating research environment in the Department of Medicine. Several other research groups at EpiGen contribute to that environment and the student will be working side by side with other researchers from breast cancer research, DNA repair, aging, Alzheimers etc. that will be inspiring and highly interesting for a young, talented and highly committed student.