Background <p>The article concerns the study of the levels of natural autoantibody to collapsin-response mediator protein&#xa0;2 (CRMP2) in the serum of the minor and major depression patients, old healthy persons and centenarians.</p> Methods <p>The purified CRMP2 was used as antigen and obtained serum samples were used as the primary antibody in an indirect ELISA test. The levels of triiodothyronine, thyroid-stimulating hormone and estradiol were evaluated in the serum samples.</p> Results <p>The results revealed insignificant increase of the autoantibody levels in the serum of the minor depression women patients and drastic, 50%-decline of their levels in the serum of the major depression women patients (<i>p </i>&lt; 0.01 on Student’s t‑criterion) relative to the middle-aged healthy women. While comparing the values of natural anti-CRMP2 autoantibody in the serum of the middle-aged healthy persons, old healthy persons (78–89&#xa0;years old) and centenarians (beyond 90&#xa0;years old), we revealed the following regularity. Relative to the middle-aged healthy persons, the levels of anti-CRMP2 autoantibody in the serum of old healthy patients declined prominently (<i>p </i>&lt; 0.001 on Friedman’s χ²-criterion). However, the values of anti-CRMP2 autoantibody in the serum of the centenarians increased drastically (by 2.3&#xa0;times) relative to the values of the old healthy persons used as a&#xa0;relevant control group (<i>p </i>&lt; 0.001 on Friedman’s χ²-criterion). The levels of triiodothyronine and estradiol demonstrated the similar dynamics as the levels of natural anti-CRMP2 autoantibody in the serum of major depression patients and old healthy persons relative to middle-aged healthy persons.</p> Conclusion <p>The conclusion addressing reliability of evaluation of the levels of natural anti-CRMP2 autoantibody in the serum of the humans as a&#xa0;proposed adaptation marker is made.</p>