3. Aging Effects on Protein Structure & Function

Vocabulary flashcards covering key terms related to how aging alters protein structure, folding, posttranslational modifications, and disease connections.

Proteostasis

The dynamic balance between correct protein folding (via chaperones) and removal of misfolded proteins (via the ubiquitin-proteasomal system).

Chaperones

Specialized proteins (e.g., heat-shock proteins) that assist other proteins in achieving or regaining their proper 3-D conformation.

Heat-Shock Proteins (HSP60, HSP70)

Major molecular chaperones induced by stress that guide folding and prevent aggregation of nascent or damaged proteins.

Protein Disulfide Isomerase (PDI)

ER enzyme–chaperone that catalyzes formation/rearrangement of disulfide bonds to aid protein folding.

Metastable Protein

A protein whose native state is only marginally stable and prone to misfolding without chaperone help.

Ubiquitin-Proteasomal System

Cellular machinery that tags misfolded or damaged proteins with ubiquitin and degrades them in the proteasome.

Protein Aggregation

Clumping of misfolded proteins into insoluble deposits, often toxic and linked to age-related diseases.

Reactive Oxygen Species (ROS)

Highly reactive by-products of metabolism that oxidize amino acids and promote protein damage during aging.

Protein Oxidation

Covalent modification of amino acid side chains by ROS, leading to carbonyls, disulfide cross-links, and loss of sulfhydryls.

2-Oxohistidine

An oxidized derivative of histidine formed during aging-related protein oxidation.

Methionine Sulfoxide

Oxidized form of methionine that can disrupt protein structure and function in aged tissues.

Dityrosine Cross-Link

Covalent bond between two tyrosine residues created by oxidative stress, stabilizing harmful protein aggregates.

Carbonylation

Introduction of carbonyl groups into proteins via oxidation, a hallmark of protein aging and degradation signals.

Posttranslational Modification (PTM)

Chemical alteration of proteins after translation (e.g., phosphorylation, deamidation, methylation) that regulates folding and function.

Phosphorylation

Reversible addition of a phosphate group (Ser/Thr/Tyr) by kinases; aging-related dysregulation impairs protein synthesis/folding.

Protein Kinase C (PKC) Pathway

Signaling cascade whose inactivation with age is linked to neurodegeneration such as Alzheimer’s disease.

Deamidation

Spontaneous conversion of Asn/Gln to Asp/Glu, altering charge and destabilizing proteins (e.g., lens crystallins in cataracts).

Methylation (Protein)

Addition of methyl groups to Arg, Lys, His (or acid side chains) that increases surface hydrophobicity, fostering misfolding.

Hydrophobic Interactions

Non-polar side-chain associations driving protein folding; weakened balance contributes to age-related misfolding.

Disulfide Bond

Covalent S-S linkage between cysteines stabilizing protein structure; formation/rearrangement aided by PDI.

Thermodynamic Stability

Energy difference between folded and unfolded states; decreases with oxidative damage in aging proteins.

Proteasomal Decline (Aging)

Age-associated reduction in proteasome activity, lowering degradation of misfolded proteins and fueling aggregation.

Chaperone Decline (Aging)

Reduced expression/function of HSPs with age, impairing folding and refolding capacity.

Proteostasis Imbalance

Combined effect of reduced chaperone/proteasome activity, increased misfolding, and aggregation during aging.

Alzheimer’s Disease (AD)

Neurodegenerative disorder linked to age-related proteostasis failure and accumulation of misfolded amyloid-β and tau.

Parkinson’s Disease (PD)

Movement disorder associated with aggregation of α-synuclein due to impaired proteostasis in aging neurons.

Cataract Formation

Lens clouding accelerated by deamidation and aggregation of crystallin proteins in aging eyes.

Protein Surface Hydrophobicity

Measure of exposed non-polar residues; rises after methylation, promoting aggregation in aged proteins.

Factors Contributing to Age-Related Proteostasis Imbalance

The disruption of proteosome/chaperone homeostasis with aging could be due to:

• Increase in protein oxidation which increases protein misfolding.
• Change in posttranslational modification of proteins leading to halt in protein synthesis and misfolding.
• Decrease in the chaperone-mediated protein folding or refolding.
• Decrease in proteasomal-mediated protein degradation.