Glycosylation Theory of Aging
The Glycosylation Theory of Aging suggests that cross-links generated
in proteins and nucleic acids
by nonenzymatic glycosylation may contribute
to age-related declines in the functioning of cells and tissues.
Nonenzymatic addition of glucose to nucleic acids may gradually damage DNA.
The reaction between glucose and proteins is known as
Maillard or browning reaction.
It begins when an aldehyde group (-CHO) of glucose combines with
an amino group (-NH2) of amino acids a Schiff base.
This combination is unstable and quickly converts to a substance known as
Amadori products. In long-lived proteins, these Amadori products slowly
dehydrate and rearrange irreversibly into structures called
advanced glycosylation end products (AGEs) . Many of these AGEs are also
able to cross-link adjacent proteins, that results in changes of important
protein's properties such as solubility, protease resistance etc.
These mechanisms are thought to play an important role in the pathogenesis
of Alzheimer disease and
atherosclerosis.
Also there is a close resemblence between some aspects of
diabetes and glycosylation due to
modifications of the extracellular matrix molecules.
For example, pentosidine,
the recent discovered crosslik between lysine
and arginine residues, appears high tissue and plasma levels in diabetic
patients and in uraemia.
Another glucose-derived advanced glycation end product,
pyrraline, is found predominantly in
the sclerosed extracellular matrix of glomerular and arteriolar renal tissues
from both diabetic and aged nondiabetic individuals.
The formation of AGEs in plasma proteins
constitutes a source of cell stimulation which induces macrophages to secrete
cytokines, interleukin-1 and tumoral necrosis factor.
The glycation process is a derivative of the
Crosslinking Theory of Aging
developed by J. Bjorksten
who documents some therapeutic
implications .
The Free Radical Theory of Aging is involved as
seen here
and in these references .
The cooking of foods accelerates the Maillard reaction and can produce
toxic substances which can lead to mutations and cancer .
Methods of study are here .
Major contributors are: