Telomerase Theory

The end of a chromosome is made up of a structure called the telosome. The tip of the telosome is a region of repeating DNA sequences and proteins called the telomere. The telomerase theory of aging suggests that there is a reduction in telomere length over time. The telosome can be thought of as being similar to the tail of a rattlesnake. There are a finite number of rings on a telosome (or a rattlesnake’s tail) and each time the telosome reproduces, 1 ring is lost. When there are only a few rings of the telosome remaining, death is imminent. It is possible to manipulate the activation of the enzyme responsible for making these rings disappear; it is called the telomerase enzyme. What is perhaps more fascinating is that certain cancers work precisely by altering the telomerase enzyme. It is thought that certain genes, called viral oncogenes, may produce immortality of a cell or tissue by activating telomerase, thus preventing telomere shortening and sustaining cellular growth of tumors. Thus, although many aspects of telomerase activity remain undefined, it has been hypothesized that the balance between telomere shortening and telomerase activity may underlie the cellular aging processes. Caution must be exercised when these genes are manipulated because of the potential to trigger cancerous change.

Dysdifferentiation Hypothesis

The dysdifferentiation hypothesis suggests that there is a preprogrammed activation of genes that are deleterious to the cell and that lead to activation of enzymes and reactions that are responsible for age-related changes. This line of reasoning was, in part, brought to the forefront from work elaborating control mechanisms of aging in the earthworm. Two main genes, BAX and BCL2, have essential roles in cellular aging and immortality respectively. Scientists were able to increase the lifespan of the common earthworm by 30% to 40% by increasing the activity of the BCL2 gene. Moderation and ethics enter the picture: the moment a cure or treatment of aging seems imminent, a potential obstacle often looms nearby. In this situation, it is known that several cancers have overwhelmed the body by upregulating the BCL2 gene. The need for caution intervenes once again.

Membrane Hypothesis of Aging

The membrane hypothesis of aging, also called the mitochondrial clock theory of aging, is based on the progressive accumulation of oxidative damage and mitochondrial dysfunction. This damage occurs secondary to the action of reactive oxygen species (ROS), also known as free radicals, which are generated in increasing quantities with age. ROS are known to damage DNA in general, and mitochondrial DNA (mtDNA) in particular, as well as cells and tissue. The mtDNA damage leads to reduced capacity for energy generation within the mitochondria and ultimately causes aging and death, which is the premise for the use of powerful antioxidants to perhaps slow the processes of aging. Perhaps more important are compounds that may safely upregulate mitochondrial function. Nuclear factor (erythroid-derived 2) –related 2, also known as Nrf2, is a transcription factor that is a master regulator of the antioxidant response. Recent breakthroughs with nrf2 activator compounds show promise for increasing endogenous antioxidants, resulting in significant reduction of oxidative stress. Nrf2 activators are currently available as functional food supplements and are being developed in pharmaceutical form.

The mitochondrion is a structure inside a cell and is the primary generator of energy, in the form of adenosine triphosphate (ATP). The mitochondria have their own DNA that determines all the functions of the mitochondria. The mtDNA is made up of 16,569 base pairs that, when intact, efficiently make energy for the body, but, if there are subtle changes in the mtDNA, there can be serious effects on mitochondrial function and energy production. Research in our laboratory as well as several others around the world have identified a specific deletion (or elimination) in mtDNA segments that is known to occur in response to aging. It is called the common aging deletion and consists of the loss of 4977 base pairs. Removal of approximately one-third of the mtDNA would cause significant problems. A primary problem is that mitochondria with this deletion can no longer produce energy efficiently. It has been found that even minor amounts of this deletion severely alter energy production and cellular function. This deletion can be measured with tools that are currently available, and this offers a molecular test for aging; although not yet commercially available, our laboratory has been studying this deletion in mice, rats, and humans since 1988. This deletion can be identified in human cells as early as 25 to 30 years of age, and there are some medical conditions in which this deletion occurs even earlier.

Studies have shown an age-related increase in the presence of the common mitochondrial deletion (mtDNA ⁴⁹⁷⁷ ). We identified the common aging deletion in 1 of 15 young rats, whereas 11 of 14 aged rats had the mtDNA deletion. The aged rats also had hearing loss, and the 3 aged rats without the deletion had better hearing compared with the 11 with the deletion. In addition, we were able to study mitochondrial function in aged rats and humans, and it is significantly reduced compared with the young subjects. Human studies have revealed the presence of this mtDNA deletion in white blood cells of patients with age-related hearing loss more often than in control patients. Two other human studies have identified the common aging deletion (mtDNA ⁴⁹⁷⁷ ) in patients with age-related hearing loss more than in control subjects. Certain tissues are more susceptible to oxidative damage (damage from free radicals) and reduced energy supply; this is especially true for tissues that no longer make new cells. For example, brain, eye, inner ear, and all muscle tissues can accumulate large amounts of these deletions, making them more susceptible to free radical damage than other tissues. Thus, increased oxidative damage that is associated with aging preferentially affects these tissues.

The process of aging is associated with many molecular, biochemical, and physiologic changes including increases in DNA damage, reduction in mitochondrial function, decreases in cellular water concentrations, ionic changes, and decreased elasticity of cellular membranes. One contributing factor to this process is altered vascular characteristics, such as reduced flow and vascular plasticity, as well as increased vascular permeability. Atherosclerosis and high lipids and cholesterol adversely affect these situations and reduce the overall blood flow to many tissues in the body. These age-related changes result in reductions in oxygen and nutrient delivery, and also in waste elimination. These physiologic inefficiencies favor the production of ROS. Furthermore, there is support in the literature for age-associated reduction in enzymes that protect from ROS damage, including superoxide dismutase, catalase, and glutathione. These changes collectively enhance the generation of ROS.

Factors in Healthy Aging

Is there hope? Can death be delayed with the tools available now? Participating in the success or failure of their own health is a clear choice that all individuals must make. Successful aging is a function of genetics, along with lifestyle and environmental factors. It is the responsibility of health care providers to educate themselves and their patients or to aggressively refer them to people who will educate and support them in making healthy choices.

Behavioral choices profoundly affect life span. Nutrition and exercise are two of the most commonly discussed elements because they are of primary importance. Enhancement of healthy aging for clinicians and patients includes identifying and managing stress, having a positive rather than a pessimistic outlook, participating in a meaningful social network, and having a support system. Other physical and emotional factors that can have a profound effect on successful longevity include environment, alcohol and/or drug abuse, tobacco use, sun exposure, marital stability, exercise, body mass index, posture, coping mechanisms, and education. Although there is little choice in genetic factors, behavioral choices can strongly affect both genetic expression and the consequences of trauma or surgery.

One of the few proven strategies to extend life is caloric restriction. This has been shown in multiple species. The mechanism is thought to relate to reduction in overall oxidative stress and a reduction in bioinflammation. It is thought that a reduction of caloric intake by 30% can lead to a 30% increase in life span. In humans, this practice would require significant reduction in consumed calories and this would mean a diet on the order of no more than 1000 to 1200 calories per day, which is enough caloric intake to maintain basic body functions; weight loss, if any, would occur quickly, a plateau in weight would be reached, and a steady state would ensue. Most people would feel hungry all the time and would not find this strategy acceptable. It has been suggested that resveratrol, the chemical found in red wine, peanuts, and so forth, can to some degree mimic the effects of caloric restriction.

This article first identifies common causes of death and then discusses contributing factors over which people have control. According to the US Centers for Disease Control and Prevention’s National Vital Statistics Reports for 2009, the most recent year for which there are figures, the 15 most common causes of death, in chronologic order, are:

• 1.
  

  Diseases of the heart

  
  
• 2.
  

  Malignant neoplasms

  
  
• 3.
  

  Chronic lower respiratory diseases

  
  
• 4.
  

  Cerebrovascular diseases

  
  
• 5.
  

  Accidents (unintentional injuries)

  
  
• 6.
  

  Alzheimer disease

  
  
• 7.
  

  Diabetes mellitus

  
  
• 8.
  

  Influenza and pneumonia

  
  
• 9.
  

  Nephritis, nephrotic syndrome, and nephrosis

  
  
• 10.
  

  Intentional self-harm (suicide)

  
  
• 11.
  

  Septicemia

  
  
• 12.
  

  Chronic liver disease and cirrhosis

  
  
• 13.
  

  Essential hypertension and hypertensive renal disease

  
  
• 14.
  

  Parkinson disease

  
  
• 15.
  

  Assault (homicide)

Nine of the 15 have well-established links to lifestyle choices centering on nutrition and exercise, and all other causes may or may not have links to lifestyle choices for any given individual. However, avoiding early death is not enough. The real question is how can aging be successful?

Nutrition

Physicians receive little education about nutrition outside of interventions for acute illness such as for renal disease, for cardiovascular disease, using total parenteral nutrition, and so forth. There is a large, varying, and conflicting amount of information in the lay press and the Internet on general nutrition. Current research indicates a plant-based diet as optimal :

• •
  

  A diet of 5 to 10 helpings of fruit and vegetables per day

  
  
• •
  

  Starches only in the form of whole grains and beans

  
  
• •
  

  Animal products severely limited or absent

  
  
• •
  

  Supplementation can be useful but should be an adjunct to a healthy diet, not to replace a healthy diet

There are virtually no nutrients in animal-based foods that are not better provided by plants ( Table 1 ).

Why have we become so dependent upon drugs, surgery, and other debilitating treatments? The answer, very simply, is this: We are sick because Nature never intended for us to eat the foods we are eating today. When looked at from the perspective of human history, the diet we are eating – loaded with fat, cholesterol, animal protein, processed foods, and artificial ingredients – is a bizarre anomaly. Our blood, arteries, and cells were not designed to live under all that fat and cholesterol that covers them today. Our intestines were not intended to work in the absence of fiber, and clogged with flesh. Our immune system was not meant to function under the burden of a thrice-daily load of fat, without an abundant supply of plant-based nutrients and phytochemicals… With our cells drowning in fat, cholesterol, animal proteins, and artificial chemicals, and our immune systems deprived of what they need to maintain health, it’s no wonder so many of us get cancer, heart disease, high blood pressure, adult-onset diabetes, arthritis, osteoporosis, and other age-related illnesses. In fact, it is a testament to the strengths of the human body that anyone has the slightest semblance of health.

Good nutrition is simple to define, but harder to practice, especially in American culture. Eat plants; that is it. In general, it is not necessary to count nutrients, proteins, or calories (but caloric restriction is an appropriate validated methodology to increase lifespan): if people eat a wide range of plants, they get all the nutrients they need, with the sole exception of vitamin B ₁₂ , which is needed as an occasional supplement but is easily obtained. Use of other supplements can be beneficial, notably antioxidants and nrf2 activators as mentioned earlier, because many of the plants that are available are grown in soils deficient of a wide range of vitamins or are picked well before ripening (and thus before uptake of available vitamins and minerals is complete). Implementing a plant-based diet within American cultural norms can be challenging; it is easy to go home and throw a steak on the grill and challenging to find low-fat or no-fat-added tasty meals in restaurants. However, there are a plethora of cook books, Web sites, and how-to books available with enough delicious foods and recipes to make people forget about animal products if they wish to move toward a plant-based diet. As with most other things, the most challenging part of changing how people eat is deciding to do so. Switching to plant-based eating can change life so much for the better that many other things that are listed in this article to achieve successful longevity will be easier to do or may no longer be as important.

There are differences among nutritionists and nutritional outlooks that are starting to converge, although traditional nutritionists still insist that people include meat and dairy in their diet, whereas the new/holistic nutritionists advocate getting proteins and calcium from the same place cows do: plants.

Antioxidants: Useful Elements for Successful Aging

Postural Distortion: Effect on Health

Postural distortion can interfere with nerve and organ function secondary to mechanical compression or referrals from trigger points. For example, severe scoliosis can cause mechanical compression of the lungs, restricting breathing and reducing oxygen levels, as well as affecting the heart ; less well known are the effects of lesser postural distortions. Any postural distortion that causes mechanical compression can diminish the function of the affected tissues. Any effect of postural distortion on tissues is not an all-or-nothing event, it is a continuum of slight to severe results. A minor problem such as constipation can stem from mechanical compression of the transverse colon, whereas a more significant problem might be hypertonic anterior cervical musculature causing a kyphotic cervical spine leading to posterior disc bulging. A trigger point is defined as a focus of hyperirritability in a tissue that is symptomatic with respect to pain; it refers a pattern of pain and ischemia when stimulated. Other referred sensations from trigger points can be numbness, itching, paresthesia, or swelling. Severity of symptoms stemming from postural distortions and from related trigger points can range from simple restriction of motion to disabling pain, the continuum of which can profoundly affect quality of life. Postural distortions and uneven hypertonicity are addressed by specific soft tissue therapies such as St John integrative neurosomatic therapy, myofascial release, Rolfing, and structural integration.

Postural Distortion and the Righting Reflex

It is necessary to satisfy the righting reflex. If this is not done, perhaps because of the sequelae of trauma or surgery, repetitive use positions, or genetics, there will then be contraction of any musculature needed to satisfy the righting reflex. This righting effort, with the influence of gravity continually pulling an individual further out of alignment, may cause an early slight postural distortion to become progressively worse over time, which is why many patients have pain symptoms that seem to have no clear antecedent.

Postural distortion is a deviation off the coronal and midsagittal planes. The greater the degrees of distortion off the coronal and midsagittal planes, the more the muscles tighten unevenly in an attempt to bring the body back to optimal posture, thus satisfying the righting reflex. An example is a garden shed that is leaning a small amount. It looks slightly off kilter but the windows and doors open easily; it functions with no problems. A year later, the shed is leaning a bit more and, although it looks the same, the door sticks or a few nails start to pop; it is symptomatic. Gravity has pulled it further out of alignment.

Symptoms Potentially Related to Postural Distortion

Once humans deviate from erect coronal and midsagittal planes, they are at risk for symptoms related to uneven muscle hypertonicity and/or trigger points: pain (back, neck, headache, abdominal), disease resulting from ischemic tissues (eg, hypothyroidism, tinnitus, low sperm count), and symptoms that seem to come out of nowhere as the organism moves further away from optimal posture. How far away from structurally erect a person can get before symptoms develop depends on many factors; some individuals have posture-related symptoms after a brief period of distortion, some individuals take decades to develop them. When long-term postural distortion is the source of the symptom, that symptom is usually not in the same location as the problem (eg, migraines caused by a leg length difference or temporomandibular joint [TMJ] pain caused by an uneven pelvic flexion).

Soft tissue hypertonicity is not detectable by any current laboratory or diagnostic imaging, so it is sometimes the forgotten differential diagnosis, but is easy to assess by someone trained in accurate postural assessment and palpation. Posture-related nerve compression and myofascial problems that are treated by cortisone injections, nerve blocks, or pain medications, and so forth only result in reoccurrences if the perpetuating factors of ongoing concentric contractions, sporadic overload, and repetitive use are not addressed.

Tinnitus, vertigo, TMJ dysfunction, throat and neck pain, among many other pain syndromes of otherwise unidentified origins, whose sufferers have failed traditional medical interventions and physical therapy, often respond well to St John integrative neurosomatic therapy (SJINT), a structurally driven therapy. A recent case study of a patient with somatic tinnitus is an example of the use of SJINT: Mr C reports that, on Thanksgiving weekend 2011, he had used a power router and consequently developed mild ringing in the right ear. Three days later he developed loud, high-pitched ringing in the left ear that has been persistent ever since. A day or two later he also had a loud ringing in the right ear, which has since been intermittent at a milder rate. He was evaluated by a Henry Ford ENT physician and the patient described his tinnitus as bilateral (left more than right) ringing with the severity of 7 to 8 out of 10, where 0 is no noise and 10 is so severe he would consider brain surgery. His Tinnitus Reaction Questionnaire (TRQ) score was 58. The patient was then referred to SJINT at the Henry Ford Center for Integrative Medicine and was found to have a right obliquity of the cranium and the pelvis, the right shoulder inferior to the left, and an uneven pelvic flexion with flexion of 10° on the left and 20° on the right; he also had an approximately 10-cm forward head posture. After treatment that day and 4 additional 1-hour sessions over the following 4 weeks treating the neck flexors, cranial musculature, right shoulder depressors, and hip flexors, and assignment of specific stretches, he returned for an audiology evaluation in which the TRQ was again administered: the patient had a score of 2 on January 27, 2012.