Highlights
- Life depends on constant protein renewal — proteins wear out faster than cells do.
- Ageing may accelerate when the body can’t keep up with repairing and clearing damaged proteins.
- Everyday oxygen-based metabolism creates reactive molecules that can damage proteins, and stressors like UV light and radiation can add extra burden.
- When protein systems struggle, the downstream effects may include declining cell function and, in some cases, longer-term changes like DNA-related alterations.
Why Protein Maintenance May Be One of the Most Important “Maintenance Systems” in the Body
A simple way to think about it: your body is constantly maintaining itself.
- Proteins do the day-to-day work inside cells.
- Cells renew and maintain tissues.
- Organs work properly when their cells function well.
Because proteins usually have a much shorter lifespan than cells or the whole organism, the authors argue that maintaining protein function is one of the deepest foundations of maintaining life.
In other words: if proteins start to fail faster than the body can repair or replace them, everything above them in the “maintenance chain” becomes harder to sustain.
Ageing as a Balance Problem: Damage vs. Cleanup vs. Replacement
The paper highlights a constant balancing act inside cells:
- Damage happens.
Normal metabolism that uses oxygen produces reactive molecules (often grouped under “ROS”) that can chemically modify proteins. Stressors such as UV light, chemicals, and ionizing radiation can also increase this burden.
- Cleanup happens.
Cells remove damaged proteins through systems such as the proteasome and autophagy (think: cellular recycling and disposal pathways).
- Replacement happens.
Cells also make new proteins to replace the ones that are damaged and cleared.
At any given moment, what we observe as “protein damage” is described as a snapshot of the current equilibrium between:
- How much damage is occurring
- How effectively damaged proteins are being cleared
- How well new proteins are being produced to compensate
This helps explain why ageing can feel gradual for years — until the system starts slipping.
The “Snowball” Effect: When Protein Damage Starts to Compound
The authors argue that when damaged proteins accumulate and protein quality-control systems can’t keep up, the effects can grow over time — like a snowball rolling downhill.
That buildup can lead to:
- Reduced cellular performance (“cell fitness”)
- Broader declines across tissues and organs
- Ageing-like changes that may be partly reversible at first, but can later contribute to harder-to-reverse outcomes
The key message is that ageing and age-related diseases may be downstream consequences of worsening protein function across the body.
How Protein Problems Could Contribute to Bigger Changes (Including DNA-Related Changes)
Most cells may experience protein dysfunction as gradual performance decline. But the paper also notes that some outcomes — like cancer — are relatively rare at the single-cell level and typically involve additional changes such as:
- Acquired (“somatic”) mutations
- Changes in DNA methylation patterns
In this framework, those DNA-level alterations may occur as consequences of damage to specific proteins responsible for maintaining DNA integrity and regulation — meaning protein damage doesn’t just affect “function,” it may also affect the systems that protect and manage genetic information.
Figure 1. Protein Maintenance Supports Healthy Aging: A Simple Balance Between Repair and Damage. This infographic illustrates the central concept discussed by Krisko & Radman (2019): healthy aging depends on maintaining “protein balance” — the ongoing ability to keep proteins functional through repair, renewal, and protective support. On the left (“Healthy Path”), chaperone-like help and protective mechanisms support proper protein function and turnover. On the right (“Damage Accumulation”), oxidative stress contributes to damaged proteins and clumping, which can overwhelm maintenance systems. As this balance tips toward damage over time, protein dysfunction may “snowball,” contributing to age-related functional decline and increased vulnerability to age-related diseases.
The Practical Takeaway
Maintaining protein quality may be one of the most important foundations for maintaining health over time. Ageing, in this view, reflects a long-term shift where protein damage and protein cleanup/replacement drift out of balance.
Reference: Krisko A, Radman M. Protein damage, ageing and age-related diseases. Open Biol. 2019;9(3):180249. doi:10.1098/rsob.180249
Link to the full paper: Read here