Epigenetics and ageing
7 important questions on Epigenetics and ageing
What is the difference between maternal undernutrition and maternal overnutrition in relation to ageing?
- IUGR-associated epigenetic programming
- catabolic processes increase
- anabolic processes decrease
- apoptosis
- insulin/leptin resistance
- impaired GH/IGF-I axis
- HPA axis dysregulation
- Macrosomia-associated epigenetic programming
- catabolic processes decrease
- anabolic processes increase
- impaired GH/IGF-I axis
- increased adipocyte size
- lypogenic enzyme activity
What are the early life determinants of ageing?
- In utero circumstances leave epigenetic mark that affects ageing trajectory
- Nutrition plays an important role, negative effects of:
- Maternal over nutrition during pregnancy
- Maternal undernutrition during pregnancy
- Catch-up phase in early life: low birth weight and high BMI at 11 years old gives highest risk for coronary heart diseases
What is the Horvath's clock?
- Best correlation with chronological age
- Input: methylation (1 or 0) of 353 CpG sites of thousands of cells (proportion methylates, value between 0 and 1)
- A formula calculates biological age from the input
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Interventions can 'rewind' ageing clock how/why
- 1 year intervention with growth hormone, DHEA and methormin
- To maximize IGF-1 and minimize insulin and induce thymic regeneration
- 1 year intervention with Mediterranean diet rejuvenates epi-clock
- Intervention with folic acid + vit B12 or flavanols decrease epigenetic age
- limited evidence of these small studies
- novel outcome of intervention trails aimed at reverting ageing
What is the theory of hormesis?
- Ageing as a decreasing homeodynamic space
- Homeodynamic space: the performance of a biological system in reaction to a specific perturbation
- stress response
- damage control
- remodelling
- Small stressors improve functioning of cell
- Defense mechanisms are triggered, cell adapt
- Stressors can be:
- ROS
- Heat/cold
- Fasting
- Nutrients
What are nutrient hormetins?
- Fasting, calorie restriction
- Flavonoids (quercini, anthocyanin)
- Polyphenols (resveratrol)
- Hypothesis: their chemical properties cause molecular damage, which is followed by a biphasic stress response
Order from low to high:
- essential lifespan
- maximum life span
- average lifespan
- Essential lifespan
- Average lifespan
- Maximum life span
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