Aging

The Way We Feel

Biomarkers

Although we know more than we did, even a few years ago, there is still a lot we don't know about aging. It is still uncertain if defects in stem cell growth and differentiation might contribute to myocardial aging or chronic heart failure (CHF). The properties of hCSCs (human cardicac stem cells) have been evaluated in dozens of studies and the results of these controlled studies and explanted hearts have demonstrated that AGE (chronological age) is a major predictor of myopathy and there are at least 5 biomarkers of senescence being studied as predictors of aging.

And there is also telomeric shorting (after each cell division those sections between chromosomes get shorter) but telemere attrition doesn't occur uniformly in all cells. This is still a mystery. A correlation was noticed however between telemere length in bone marrow cells and in cardiovascular diseases.

Dysfunctional (shortened) telemeres have been demonstrated as biomarkers in AGING and in heart failure patients. The lastest study I'm aware of took place just this year (2011).

Scientists have been studying the mechanism that determines the aging process and while much is still unknown about why we age, during the last ten years, evidence has been pointing in the direction of the hypothesis that mitochondrial damage may be at least ONE major factor in the aging process. This is understandable because of the importance of mitochonria and energy production. Without it we would not be here. We might be plants and depend on chloroplasts instead of mitochondria for our energy production.

Research does indicate that mutations (oxidation is the major suspect but not the only one) in mitochondrial genes which result in some degenerative diseases of the central nervous system (CNS), the heart, the skeletal muscles, the kidney, and the endocrine (hormonal) system and this is amply demonstrated by complaints, quite common, among the elderly - and some not so young but as they age. Two complaints which may also be age related are fibromyalgia syndrome (FMS) and mild cognitive impairment (MCI).

To reiterate, clinical manifestations of these disease processes are common complaints among the aging population.

Mitochondria produce cellular energy and this is also the primary source of oxidative stress from endogenous oxygen radicals - an accumulation of these free radicals in the cellular machinery has been associated with aging and damaged cells.

Postmitotic tissues accumulate mutations in somatic mitochondrial DNA (mtDNA) with age. This correlates with an age-related decline in mitochondrial functions - and an eventual programmed cell suicide (apoptosis).

Studies conducted with mice establish the hypothesis of deficient ATP mitochondrial energy production and increased reactive oxygen species (ROS) detoxification with aging. The mice exhibited the symptoms of degenerative disease (and aging). *(The theory is still being tested and experimental)

In mitochondria the process called oxidative phosphorylation (OXPHOS) which occures within the inner membrane. Mitochondria is the energy generation factory for each cell. During OXPHOS, hydrogens are derived from dietary carbohydrates.

(The process is complicated, the details for which, seem unneccesary for here - it is a big deal now in biology classes in high school - understanding the KREBs cycle and ATP, though when I was in high school it was not even understood.)

During this process of energy production and oxygen leakage - a superoxide anion; besides the normal ions produced, very toxic superoxide radicals are also produced which damage and ultimately destroy a cell.

(Superoxide anion is a toxic byproduct of OXPHOS, generated by the transfer of electrons.)

Red cell blood (you know, those little red globs that look almost like donuts without a hole; there is a concave indentation in the middle or center of them and they are very flexible) concentration is about the same in the elderly; about but not exactly the same. It is the same with the blood volume. It is because the elderly are less active. The blood volume is constant until very late in life; about 80 years of age. It may decrease somewhat then but the volume stays the same, however tissue mass has decreased as your age so there is more blood volume to go around. Anotherwords, there is more blood volume in relation to the amount of tissue the elderly have. The elderly have less tissue but plenty of blood.

When you have blood lab work done, your physician may order up an erythrocyte sedimentation rate (ESR) test. They take a sample of blood, put in an anticoagulent and let it stand. It is a timed test and is an easy and inexpensive test. The red blood cells settle out. This is a screening test for acute and chronic inflammation. It is timed because whenever you have inflammation your blood settles out faster than it would otherwise. It can indicate cancers, inflammation, autoimmune diseases but it is non-specific. It does not tell you exactly where the anamoly is occurring. It just tells you something is wrong, but not where. But it is a good diagnostic tool. Other testing can determine where the problem is or a patients complaints can be the key to correctly diagnosing the exact problem. An ESR is also used for monitoring disease and response to treatment.

With age the SED rate increases slightly so when we look at the ESR from an older person it may indicate an elevated inflammation rate.

An ESR test is also very useful for diagnosing temporal arteritis, chronic inflammation and damage of large arteries in the face and head; symptoms include scalp tenderness, headaches, loss of vision and facial pain. And it is particularly useful in diagnosing polymyalgia rheumatica which causes pain in the neck, shoulder muscles and pelvis, morning stiffness, common among women more than men in their 50s and older.

Other tests your doctor may order if any of these symptoms prevail would be a CBC, a CRP, ANA, RF and others - ESR is a better marker for inflammation, but C-reactive protein (CRP) is also a good marker for inflammation.

Viscosity; that is the thickness of the blood, also increases slightly with age. And in both the ESR and the viscosity the increase in both, in older persons, is likely the increase in the concentration of fibrogen. Fibrogen is like a glue, it is protein in the plasma (and in tissues and muscles) and more protein will make blood thicker.

Red blood cells slow in circulation especially in older folks BUT ALSO in the handicapped and anyone not all that active (though that is only one cause), and the red blood cells will line themselves up. When red blood cells stand, they line themselves up; they stack themselves; this is called rouleux, the worst stage of protein linkage and results in fatique, poor circulation, shortness of breath, cold hands, feet, etc. A major cause is eating too much meat (too much protein and poor digestion of protein), blood becomes toxic from stress, pancreas may be not working as well as it should, dehydration, too much coffee, etc. AND, this is one of the top most undiagnosed causes of many ailments.

(Rouleux will compromise the red blood cells ability to exchange carbon dioxide and oxygen gases. If you suspect a problem, you should see your physician immediately.)

In rouleux formation of the blood cells, the membranes, the outer layer of the lipid bylayer is lining up and causing them to fuse together in that formation. There is a relationship to inflammation; if we have blood that line up and form rouleux formations more rapidly, it causes the blood to settle out more rapidly thus increasing the sedimentation rate or ESR faster than it would otherwise.

People who have more inflammation - at any age - have a tendency for increased concentration of plasma proteins which cause this dysfunctional fusing, this rouleux and they settle out more rapidly. The increased fibrinogen in the elderly (fibrinogen is protein) leads to increased viscosity (thick blood). A fibrinogen activity test may also be indicative of bleeding disorders and a thrombotic episode. You could also have a rise (elevated fibrogen test) in a fibrogen activity test from a stroke, cancer, acute infections, a heart attack, inflammatory diseases, trauma and cardiovasular disease.

There is no significant changes in platelets or in white blood cells in the elderly. However, we do have more fibrogen in elderly folks.

Just a few comments about inflammation. We have endophilic retraction which causes capillary permeability and things leak out and some of what leaks out are plasma proteins. Proteins are just going to leak through the capillary walls; there are no pumps. Another words, proteins just go from where they are more concentrated to where they are less concentrated. That is just the way it works. They are more concentrated in the plasma than in the interstitial fluid so we get more movement out of the capillaries than into the capillaries. The interstitial fluid is the liquid found between the cells of the body that provides much of the liquid environment of the body. The online Free Dictionary says, the "extracellular fluid - liquid containing proteins and electrolytes including the liquid in blood plasma and interstitial fluid (the body normally contains about 15 quarts of this fluid).

There are plasma proteins that are of particular importance to us with regard to inflammation. There are the complement proteins. Over 25 proteins and protein fragments make up the complement system which are part of the immune system which helps (complements) antibodies to clear pathogens from an organism. These are interacting plasma proteins that activate in a cascade (they act upon each other). These are defense proteins. Serum albumin is the most abundant blood plasma protein and is produced in the liver and forms a large proportion of all plasma protein. The human version is human serum albumin, and it normally constitutes about 60% of human plasma protein.

Albumin is sticky and a major transporter in interstitial fluid. Albumin is the main protein of plasma; it binds water. The Free Dictionary states, "Serum albumins are important in regulating blood volume by maintaining the oncotic pressure (also known as colloid osmotic pressure) of the blood compartment." It is the main transporter. There are also a lot of clotting proteins for obvious reasons.

When complement plasma proteins are activated stimulating mast cell degranulation - "mast-cell degranulation, leading to the rapid release of inflammatory mediators, such as histamine, proteoglycans, and cytokines. Mast-cell activation also stimulates the arrival of other inflammatory cells - a critical step in local inflammation." (Respiratory Reviews)

Inflammation is an important defense mechanism. Mast cells release histomine which cause the inflammation. Once we release more complement proteins, and more Phagocytes-Neutrophils are activated more mast cells activate more inflammation. Without getting any further into this topic than I need to, it should be enough to understand a process is started here which mediates inflammation by recognizing what is out of place and then defending against it. "Phagocytes are cells which ingest particles. The process of eating particles is called "phagocytosis," a process which is one of the distinguishing features of eukaryotic cells, found even in such primitive organisms as the amoeba, Chaos chaos, which hunt, ingest, and kill microbes for nutritional purposes." (Dr. Ken Miyasaki) Inflammation is part of the process and all these other actions. It all works together to maintain internal constancy and provide for an environment which is in homeostasis.

Controlling inflammation, oxidative stress and other stress could be the ticket for enjoying a healthy old age and remember fellow vampires, there is a full moon tonight. Stay hydrated - Drink plenty of blood.

(There are a lot of theories about aging, but a whole lot of testing needs to be done and often the results in some of these trials although they may seem positive during initial testing won't stand up under additional research. The jury is out on why we age.)

Aging

The Way We Feel

Biomarkers

Hank Roth