📕 Lecture 4: Mechanisms of Disease

List key mechanisms linking environment to disease.

Mechanism	Description
Inflammation	Chronic low-level inflammation promotes cancer, CVD, etc.
Barrier dysfunction	Damage to skin/lung/gut barriers leads to disease (e.g., eczema, asthma).
Oxidative stress	Reactive oxygen species damage DNA, proteins, lipids.
Mitochondrial dysfunction	Alters energy production, accelerates ageing.
Cell senescence	Aged cells that can't divide; secrete inflammatory signals.
Epigenetics	Environmental cues change gene expression without changing DNA.
Stress (HPA axis)	Chronic stress → cortisol dysregulation → immune suppression.
Microbiome	Imbalanced gut flora = dysbiosis → links to obesity, diabetes, immune disorders.

What is cellular senescence?

Permanent cell cycle arrest causing inflammation and impaired tissue repair.

How does chronic stress affect the body?

Chronic stress → activation of the hypothalamic-pituitary-adrenal (HPA) axis:

• CRH → ACTH → cortisol: The hypothalamus releases corticotropin-releasing hormone (CRH), which tells the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH then signals the adrenal glands to release cortisol.

• Prolonged cortisol → metabolic dysfunction, immune suppression.

What is the microbiome and its purpose?

The collective microorganisms and their activity in a specific habitat (e.g., gut, skin, lungs) and is crucial for metabolism, immunity, and inflammation.

What are epigenetic modifications and what are they caused by?

Heritable changes in gene expression without altering DNA sequence (e.g., methylation, histone modification).

Epigenetic changes caused by:

• Diet, stress, pollutants, infections.

Long-term effects on disease risk (e.g. obesity, cancer, mental illness).

What is Pathogenesis and Aetiology?

• Pathogenesis: How diseases develop.

• Aetiology: Cause of disease (can be genetic, environmental, or infectious).

What is Dysbiosis?

Dysbiosis = imbalance → contributes to NCDs.

What is 16S rRNA sequencing?

16S rRNA sequencing = used to identify microbial composition.