The "AGE"-ing You've Never Heard Of – Part 2

Written by Anil Bajnath, MD
Posted October 14, 2021

Dear Longevity Insider,

Thousands of advanced glycation end products (AGEs) have been identified from the glycation of proteins and lipids on y-positioned amino groups of lysine residues or oxygen-containing groups such as the following : aldehydes, ketones, and reducing sugars.  

  • Aldehyde is a compound containing a functional group with a carbon atom double-bonded to an oxygen atom and single bonded to -CHO. This carbon and oxygen is called a carbonyl group. 
  • A ketone contains a carbonyl group bonded to two other atoms such as the following: R-COCH= O (R= alkyl, aryl, etc.). 
  • Reducing sugars is a term used for monosaccharides and some disaccharides that can be oxidized to form aldehydes or ketones.

Some of the AGEs that can be found in our bodies are: N ε -(carboxymethyl)lysine (CML), pentosidine, and others. CML and pentosidne is considered as a reliable biomarker for oxidative stress and damage to DNA, RNA, and protein. Additionally, pentosidine and CML are biomarkers for type 2 diabetic retinopathy. Oxidative stress refers to the damage produced in cells and tissues by non-neutralized free radicals. Oxidation is a process in which the structure of an organic compound is altered by the addition or removal of electrons to its molecules or atoms, causing it to become oxidized. Oxidation is dangerous to the body because it creates a chain reaction of oxidative stress.

Impact of AGEs on Inflammation, Oxidative Stress, and Insulin Resistance

AGEs can disrupt cellular communication. Cellular communication refers to the internal biochemical messengers that carry information from cell to cell. Cellular communication makes up an important part of normal body function, allowing cells to "talk" to one another and coordinate various functions necessary for the body as a whole (like growth, tissue repair, and organ function). AGEs interfere with cellular communication by binding to the surface molecules on cells. Examples of this include altering cell surface receptor function (such as the insulin and/or IGF-1 receptor), increasing cellular inflammation (via NFκB), and increasing oxidative stress.

AGEs have a direct impact on proteins and the extracellular matrix. The extracellular matrix is our body's natural scaffolding that supports our cells. (Cells are attached to extracellular matrix, and AGEs accumulate in this area.) AGEs causes damage to cellular proteins and the extracellular matrix by oxidative stress. AGE crosslinks have been documented to contribute to retinal capillary cell death, diabetic nephropathy, atherogenesis, etc.

Additionally, AGEs can alter cell intracellular signalling by AGE-RAGE (AGE receptor AGE). AGEs have been suggested to being the cause of oxidative stress, inflammation, and insulin resistance. AGEs are linked to inflammatory markers like C-reactive protein (CRP) present in the blood, which is an indicator of systemic inflammation. 

Mobility and Aging

Mobility is one of the most common problems that elderly people face. Mobility refers to the ability to perform the basic activities of daily living that are necessary for independence and is a core indicator of health and quality of life in aging. In older adults, the decline in physical function is a major determinant of frailty and loss in independence.

The age-related decline in physical function results from a number of changes that occur at the cellular, organ system and whole-body levels. AGEs are linked with degradation of skeletal muscle function in older adults. AGEs are also known to play a role in the pathogenesis of arterial stiffness and hypertension, both strong predictors of cardiovascular disease which is one of leading causes of death among the elderly people.

Reverse AGEs

Reversing AGEs requires reversing AGE modifications at the molecular level. Since AGEs are modified by sugars, avoiding foods high in sugar and avoiding processed sugar are generally recommended. In addition to reducing or eliminating sugar intake, antioxidant-rich foods should be consumed to reduce oxidative stress.

Additionally, supplements that promote healthy blood circulation may reduce the body's exposure to AGEs. Some supplements that can support reverse AGE modification include carnosine, aminoguanidine known as pimagidine and benfotiamine.

Unfortunately, there has been a challenge in reverse AGE at the molecular level but this challenge has led to the development of AGE inhibitors. Such inhibitors are now being developed for therapeutic use in order to manage diabetic complications and other diseases that result from AGE modifications at the molecular level. Examples include therapies targeting collagen cross-linking, glyoxalase I inhibition, or amadoriase gene expression.

Not only are modifications being made at the molecular level, but there are age-related processes happening at the cellular level as well. You see, the body goes through a process called cellular senescence. It's where your cells continue to divide into more cells. But this process hits a capping point where said cells stop splitting and become toxic.

Studies attribute these toxic cells to causing many "age-related" diseases. The most fascinating part about these cellular inner workings is another process called autophagy.

Doctors and scientists alike have seen the reverse influence autophagy can have on these toxic cells.

Here's the data.

To your longevity,

Anil Bajnath MD
CEO/Founder, Institute for Human Optimization
Chief Medical Officer, Longevity Insider HQ