Why do we age? Can we stop or slow our aging?
Can age-associated diseases such as Alzheimer’s, heart disease and cancer be prevented or their symptoms delayed? Only recently has science developed the tools to delve into the intricacies these questions raise.
Functions of mitochondria
The mitochondria – the organelles within our cells, where energy, in the form of the chemical ATP, is produced – are a serious focus for scientists involved in aging research. Healthy, robust mitochondria are essential for a long healthy life. New research sheds more light on how the mitochondria affect our health and our lifespan. But first a little history of why these organelles are believed to play a role in aging and in the development of age-associated diseases.
Over fifty years ago a scientist named Denham Harman worked on a government-sponsored project to investigate the effects of radioactive material on human tissues. His work led to the discovery of the presence of unstable compounds (free radicals) produced in animal tissue exposed to radiation. Harman observed that over time tissues of these animals accumulated biological defects that resembled premature aging. In other words, the animals were getting older before their time. Because the sequence of events in the radiation-exposed animals mimicked accelerated aging, he reasoned that the normal aging process might result from the accumulation of tissue damage caused by free radicals. This work gave birth in 1954 to Harman’s Free Radical Theory of Aging.
Even in the absence of excessive exposure to radiation, we all age. Thus a major hole in this theory, recognized at the time, was the origin of free radicals present in the tissues of animals not exposed to radiation. It was not difficult to measure large amounts of free radicals produced by radiation, but at that time tools were not available to measure the smaller amount of free radicals in tissue.
Following the development of new investigative tools, scientists demonstrated that free radicals are indeed produced by normal cellular processes and that the majority of these toxic substances are produced during the production of useable ATP energy in the cell’s mitochondria. Thus, the Free Radical theory morphed into the Mitochondrial Theory of Aging in 1972.
This latter theory states that the mitochondria are the source of the free radicals that initially damage the mitochondria, and with time the cumulative damage to these organelles results in the decline of cellular health and eventually cell death. Therefore, one can conceptualize the mitochondria as cellular-time capsules. At birth or perhaps even during fetal development, the clock begins to tick!
The story is not yet complete, however. Free radicals are toxic to the cell, and the body can make free radicals, but this does not prove that the damage produced by free radicals to the mitochondria actually causes aging. Damaged mitochondria might be an effect of aging and not the cause!
New support for the Mitochondrial Theory of Aging was recently presented by investigators in Sweden. They developed a mouse model to answer the question of cause or effect. Working with the mouse genome, they carefully inserted a defective gene that would result in progeny with impaired capacity to repair defects in the mitochondrial DNA. This mimicked the aging process, as it has been clearly demonstrated that cumulative mitochondrial DNA damage is associated with aging.
For the first 25 weeks of life (comparable to a human teenager in age), the mice were normal in all respects. However, beginning with the 25th week, the animals began to look different from their normal (non-defective) mouse counterparts. They began to show typical signs of premature aging, such as spotty baldness, curvature of the spine, osteoporosis and decreased energy (lethargy), all characteristics common to human aging. Furthermore, the mice’s lifespan was cut from three years to between one and two.
Examination of the mitochondria taken from animals of different ages clearly showed defects in the mitochondrial DNA, as well as other mitochondrial structural components. This damage was cumulative. In other words, there was very little damage in the first few weeks and a steady increase in damage with time. Apparently, it takes a certain amount of damage to the mitochondria to create a physically observable age-associated lesion, and it takes about 25 weeks to reach that critical mass for the defective mice. The normal mouse counterparts also had cumulative DNA damage but to a much lower extent.
This experiment clearly suggests that mitochondrial damage is a cause and not an effect of aging. It also demonstrates that normal aging is likely the result of the accumulation of cellular errors.
The authors of this study intend to pursue this model of aging to determine whether the mitochondria of these prematurely aging mice produce an elevated quantity of free radicals. It has been demonstrated by others that aged mitochondria – those with increased defects – produce an increased quantity of free radicals, which further speeds up the aging process. This model of aging supports the idea of intervening in the aging process with agents that can neutralize the age-associated increased production of free radicals. It also raises questions about what agents and doses are most effective. Perhaps the biological clock can be reset!
It is clear that DNA mutations accumulate with age in all species studied, including humans. The probable mechanism for this damage is through the attack by toxic oxidants produced in the mitochondria.
Variation in lifespan among people may reflect, in part, the efficiency of the antioxidant defense systems we inherited, as well as environmental factors. The long-lived individual probably has the most effective antioxidant defense system. Abstaining from tobacco, participating in a regular exercise program and obtaining the optimum amount of nutrients from diet and supplements also has a significant supportive effect on the antioxidant defenses that control damage to the mitochondria.
A nutritious diet high in fruits, vegetables and legumes, should help maintain healthy mitochondria. Evidence from animal studies supports supplementing our diets with certain vitamins, such as E and C, as well as acetyl-L-carnitine and the antioxidant alpha lipoic acid. These nutrients may provide additional support for the cellular antioxidant defense system in supporting mitochondrial health. Finally, exercise is of utmost importance in promoting mitochondrial health. Exercise helps keep the machinery in an oiled-up, active condition, and at the same time prevents the accumulation of fat-promoted, toxic free radicals.
Cause or effect? For years, scientists have observed that cumulative mitochondrial DNA damage is associated with aging. They were uncertain, however, whether this damage actually causes aging. A recently published article in the journal Naturereports on a study performed at the Karolinska Institute in Stockholm, Sweden.
The researchers developed mice with genetically impaired ability to defend their cells against free radicals. They then demonstrated that the impaired mice aged much faster than wild-type mice. Their symptoms included premature spinal curvature, reduced hair density and other signs of aging The experiment clearly suggests that free radicals cause aging.
This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.