Genetic Variants in Autophagy and Aging

Study Notes

Master thesis pursued by Izzeddin Halawa in Biology, focusing on Molecular Genetics, Cell and Developmental Biology.

Investigation of genetic variants (SNPs and indels) in autophagy and aging-related genes in dogs through bioinformatic methods.

Autophagy is a cellular process that degrades and recycles damaged components.
It consists of three major types:
- Macroautophagy
- Microautophagy
- Chaperon-mediated autophagy.

Initiation begins at the endoplasmic reticulum, forming a pre-autophagosome requiring proteins like ULK1 and ATG13.
Proteins involved in further steps include:
- VPS34, VPS15, and Beclin 1, which facilitate the production of PIP3.
- WIPI proteins and cargo receptors like P62 and NBR1 recruit substrates.
- LC3-1 and the ATG protein complex (ATG5, ATG12, ATG16) are critical for targeting substrates for degradation.
Mature autophagosomes fuse with lysosomes to degrade contents through acidic proteases like cathepsin B.

Aging leads to cellular integrity decline, characterized by the accumulation of faulty macromolecules.
Research suggests that interventions in conserved signaling pathways might modulate aging processes and offer therapeutic potential.

Autophagy reduces inflammation, a contributor to various chronic diseases.
Enhances immune system function and supports recovery from stress conditions.
Contributes to skin health, reduces wrinkles, and helps maintain brain function, potentially protecting against diseases like Alzheimer's.

Genetic variants, including SNPs and indels, can influence disease susceptibility and responses to medications.
SNPs represent single base substitutions in the DNA sequence, with around 10 million present in the human genome.
Indels refer to insertions or deletions that can cause frameshift mutations, altering the protein's amino acid sequence significantly.

Single Nucleotide Polymorphism (SNP)
- Variation at a single base pair that accounts for many genetic differences among individuals.
Insertions and Deletions (Indels)
- Cause frameshift mutations, disrupting coding sequences, leading to potentially nonfunctional proteins due to incorrect amino acid sequences.