Advanced glycation end products (AGEs) result from the nonenzymatic glycation of proteins and contribute to tissue damage, particularly in conditions like diabetes. AGEs can originate from both external sources, such as diet and tobacco smoke, and internal physiological processes, leading to complications like diabetic neuropathy, retinopathy, and vascular issues. The body has defense mechanisms against AGEs, including immune responses that help to clear these harmful compounds.

1. Advanced Glycation End
Products

2. Prolonged exposure to elevated glucose concentrations
damages tissues by causing either to increased sorbitol
pathway activity and glycosylation of proteins or
cumulative irreversible formation of advanced
glycosylation end products (AGE) on matrix proteins
such as collagen and on nucleic acids and
nucleoproteins.

3. Nonenzymatic glycation is a process by which
glucose is chemically bound to amino groups
of proteins but without the help of enzymes.
During the process of glycation, early glycation
products are formed first, which subsequently
rearrange into final AGE structures through a series of
very complex chemical reactions.
Advanced Glycation End Products
(AGE)

4. BIOCHEMISTRY OF AGEs FORMATION
AGEs can be formed exogenously and
endogenously.
EXOGENOUS SOURCES
AGEs can be introduced into
the body from
the following sources;
- Tobacco Smoke
- Diet
ENDOGENOUS SOURCES
AGEs accumulate during the
physiological aging process.

5.  The body does have a defense against cross-linked
proteins.
The immune system has a
receptor for AGEs. The
macrophages engulf AGEs and
Eventually the products are
excreted in the urine
AGE receptor

6. AGEs in diabetic vasculopathy and atherosclerosis
LDL from the circulation binds to AGE-modified
collagen of the blood vessel walls. (Vascular tissue AGE
accumulation cause protein crosslinking & oxidative
damage

7. AGEs and renal failure
AGEs can induce an excess crosslinking of collagen
molecules in the glomerular plasma membrane
affecting the
assembly and architecture of the glomerular basement
membrane and mesangial matrix
.

8. AGES and diabetic neuropathy and retinopathy
In neuropathy
Nonenzymatic glycation of
axonal proteins causes
alteration in structure and
transport, leading to axonal
atrophy and degeneration..
Axonal cytoskeletal proteins
have essential roles in axonal
structure and function.
In retinopathy
 AGE-modified albumin co-
localizes with the component of
AGE receptors in the retinal
vasculature