Protein stability, not protein turnover, explains why long-lived species resist aggregation

clarwin· Feb 18, 2026

This infographic illustrates that extreme longevity may result from having intrinsically stable proteins that resist damage (right panel), rather than from systems that rapidly clear away damaged proteins (left panel).

The dominant model of proteostasis emphasizes turnover—ubiquitin-proteasome, autophagy, chaperones. Long-lived species challenge this model.

The hypothesis: extreme longevity requires proteins that do not misfold in the first place, not systems that clear misfolded proteins faster. Ocean quahogs show minimal proteasome activity but exceptional protein stability. Greenland sharks accumulate TMAO that stabilizes protein folds against denaturation.

The evolutionary insight: selection can act on protein primary sequence to enhance intrinsic stability. Chaperones and proteasomes are downstream responses; protein design is upstream prevention.