The essential mechanisms of aging: Irreparable damage accumulation of biochemical side-reactions.

Explanations on aging mechanisms have now become unexpectedly complicated. However, it is gradually accepted that 'senescence is a collective consequence of both inheritance and environment'. Based on the achievements of biological and medical research in related fields, we pinpoint in this review that although aging is mainly considered a physiological (non-pathological) process, the biochemical structure of aged organisms is deranged, or 'sick' at the molecular level. The free radical/glycation induced carbonyl stress, the key culprit to form crosslinks, has been identified to cause stable cyclic conjugates of mainly protein-based aggregates implying entropy increase (the Second Law of Thermodynamics) during aging. When combining such key aging processes with age pigment biochemistry, a general picture of aging process can be figured out, as the main clues and results are available. In this review we also propose for the first time that by focusing on 'process' rather than on 'causes' (damages), we can then get a clear view of aging mechanisms. Through rational thinking and critical analysis, we conclude that the accumulation of irreparable damages and alternations caused by spontaneous biological side-reactions seems to be the essential and profound nature of higher animals' aging mechanisms.