Life Extension Magazine

Life Extension Magazine January 2004

Pathways of Aging

Carnosine Extends Animal Life Span
Carnosine may appropriately be called an agent of longevity; in animal studies it extended the life span of senescence-accelerated mice by 20% on average compared to mice that were not fed the supplement, and doubled the number of mice who lived to old age. The researchers concluded that, in addition to extending the lives of the mice, carnosine significantly improved their appearance, physiological health, behavior, and brain bioch emistry.36-38

Unfortunately, our natural levels of this important dipeptide decline with age; muscle levels, for example, are reduced 63% between the ages of 10 and 70, which researchers speculate may explain why our muscles tend to decline in both mass and function as we age.39 And although we can replenish some of the carnosine we need by eating meat (a main dietary source of the dipeptide), with so many of us cutting back on this source of protein today, taking a carnosine supplement is often necessary.

Guarding Against Hormone and Immune Decline
Our neuroendocrine and immune systems declines as we grow older, and laboratory studies suggest that this may cause these systems to send inflammatory chemical signals that contribute to cell death or senescence—and may even have an effect on life span.40

Moreover, as we age and our neuroendocrine systems stop working at peak performance, there also is a decline in levels of the essential polypeptide hormone insulin-like growth factor 1, or IGF-1 (also called somatomedin C).41,42 IGF-1 circulates in the blood to each cell in the body, coordinating cellular function and regulating cell growth and division.

What exactly is IGF-1? When human growth factor, or HGH (often called the “Fountain of Youth” hormone) enters the blood stream from the pituitary gland, it is taken up by the liver and converted to IGF-1, which binds with cells throughout the body, including the brain, exerting a growth effect. IGF-1 is in fact responsible for many of the age-defying effects attributed to HGH—and a decline in IGF-1 is thought to result in a reduction of cell activity.43

Research shows that IGF-1 increases insulin sensitivity and lean body mass,44 reduces fat, and builds bone, muscle, and nerves,45,46 which is why it can reverse many of the physical signs of aging. These include loss of muscle strength, mass, and endurance, sagging skin and wrinkles, uncontrolled weight gain, joint pain and inflammation, decreased energy, loss of flexibility, and digestive problems. Researchers say that one of IGF-1’s greatest benefits, however, is its ability to repair peripheral nerve tissue that has been damaged by injury or illness.

Shortages or imbalances of IGF-1 are now thought to be a key factor in the aging process and in the development of aging-related health woes such as Alzheimer’s disease,47 type II diabetes (and its complications such as diabetic retinopathy), Syndrome X (aka metabolic syndrome), artherosclerosis and heart disease,45,48-50 and Lou Gehrig’s disease,51 as well as difficulties recovering from surgery and trauma. Recent research has revealed that higher levels of IGF are not a factor in the development of prostate cancer, as previously speculated.43

A three-dimensional MRI showing a normal brain, highlighting the pituitary gland and the pituitary stalk (yellow).

Within the last four years, researchers have associated low IGF-1 levels with beta amyloid, the putative cause of Alzheimer’s disease,47 amyotrophic lateral sclerosis/Lou Gehrig’s disease,51 ischemic heart disease49 and carotid atherosclerosis in elderly men.49

In a newly published study, 54 hypertensive patients were followed to determine their risk of developing carotid atherosclerosis. Multiple logistic regression analysis revealed that insulin-like growth factor binding protein 3 (IGFBP3) level was associated with a ninefold higher risk of carotid plaque formation compared to LDL cholesterol or IGF-1 levels. It can be inferred that low levels of free IGF-1 are a risk factor for this disease.52

In a study of asymptomatic subjects infected with HIV-1, the hypothesis that oral administration of three grams per day of acetyl-L-carnitine could significantly affect IGF-1 levels was tested. The researchers found that while acetyl-L-carnitine did not raise total IGF-1, it significantly increased levels of free IGF-1 (the bioactive component of total IGF-1) in the treated patients. The researchers stated that none of the subjects investigated reported any toxicity directly or indirectly related to acetyl-L-carnitine administration. Remarkably, all the treated patients reported, subjectively and without exception, an improved sense of well being by the second and third week of acetyl-L-carnitine therapy.53

Finally, a recent study suggested that higher growth hormone/IGF-1 levels in adulthood play a determinant role not only for regressive manifestations (chronic diseases) but also for life potential (longer life span).46

Summary
Aging is a multifaceted process. Scientists have found that many of the molecular mechanisms that cause disease and premature aging are interrelated. These interconnected pathways provide a basis for humans to counteract these destructive age-related processes.

We now know that free radical damage directly causes cellular energy depletion, and that these energy-depleted cells then generate more toxic free radicals. Even more insidious is that these energy-depleted cells may not go through normal apoptotic-removal processes, but instead send out signals that attract destructive inflammatory cytokines that in turn damage healthy cells. Energy-depleted cells that fail to undergo normal apoptotic removal become chromosomally instable and are much more vulnerable to transform into cancer cells. Therefore, a clearly established mechanism now exists to explain how aging cells are more likely to turn cancerous, in addition to malfunctioning in a way that will eventually lead to debilitation or death.

An increasing number of scientific studies reveal that sugar toxicity is a causative factor in a host of degenerative diseases and premature aging. One only has to look at the multiple diseases suffered by diabetics to appreciate the lethal effects of protein glycation and carbonylation, major complications related to excess sugar (glucose) levels. Non-diabetics also encounter these destructive, protein-damaging glycation and carbonylation processes, albeit at a slower rate than diabetics.

Taking steps to guard against glycation would appear to be a mandatory part of a health maintenance program. Dietary modification and aggressive control of blood sugar levels reduce glycation reactions. For instance, avoiding food cooked at high temperatures appears to reduce the formation of AGEs in the body. Higher blood glucose levels facilitate glycation processes, so keeping blood glucose in lower normal ranges is recommended.

Carnosine and benfotiamine appear to be the most effective nutrients to reduce glucose-induced cellular damage. Carnosine protects against glycation, carbonylation, copper-zinc toxicity to brain cells, DNA fragmentation, and dangerous free radicals. Benfotiamine blocks the absorption of excess glucose into cells and protects against glucose-induced cellular toxicities.

Aging humans accumulate excess body fat, suffer energy deficiencies and occluded arteries, and encounter various forms of neurological impairment. Deficiencies in carnitine play a role in these disorders through multiple pathological mechanisms. Not only has acetyl-L-carnitine been shown to enhance mitochondrial energy function, but it also boosts levels of free IGF-1, a hormone necessary to maintain youthful cellular function throughout the body. As people reduce their consumption of foods high in carnitine, supplementation with bioavailable acetyl-L-carnitine appears to be a prudent way of ensuring optimal daily intake of this important nutrient.

Humans seeking to live a healthy extended life span can take relatively simple steps to protect against today’s known causes of premature aging and degenerative disease.

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