Incredible scientific discoveries that will change the way we look at aging and disease have been unfolding during the early 21st century. The secrets for healthy, youthful aging, while clearly influenced by our behavior, appear to be rooted in mechanisms at the molecular level of our cells. In 1990, the journal Nature published a groundbreaking article based on something called the telomere. It changed forever our understanding of the aging process. Last year, the Nobel Prize in Medicine was awarded to scientists for their discoveries of the role of telomeres, and the enzyme telomerase, in aging, cancer and chronic diseases. But are telomeres the whole story?
We all would like to wrap up aging into one neat package for which a single curative pill or intervention could be discovered (the fountain of youth), but nature is usually not that simplistic. Any explanation of the aging process must take into account the complexity of maintaining the integrity of genetic material (genome), managing energy production through the master metabolic regulators such as sirtuin genes[1], defending against oxidative stress from reactive oxygen species (free radicals), activation of tumor suppressor pathways and the state of the cytokine (chemical messengers) environment around the cells[2]
The fundamental defining manifestation of aging is an overall decline in the functional capacity of various organs to maintain baseline tissue homeostasis and to respond adequately to physiological needs under stress.[3] In most individuals, this decline is gradual over many years, only accelerating in later life. Moreover, the decline differs among the various organ systems. A typical element of that decline is a diminished response to physiological insults or stressors rendering the individual increasingly susceptible to disease. Accordingly, age is the major risk factor for the development of chronic diseases and cancer. Specifically, between ages 40 and 80, there is a rapid increase in cancer incidence that produces an overall lifetime cancer risk of nearly one in two individuals in industrialized nations. [4]
In youth, and throughout most of our lives, we have a remarkable capacity for extensive tissue renewal mediated through reservoirs of tissue specific stem cells.[5] Preserving an adequate pool of tissue stem cells with a robust potential for renewal is vital to maintaining organ function with advancing age. Research has demonstrated an age-associated decline in functionally competent stem cells in multiple organ systems mediated though several molecular pathways and as a result of diminished mitochondrial function.
Mitochondria are the cellular “power plants” responsible for converting dietary fats and carbohydrates into ATP; the essential source of energy for the cell. ATP is analogous to the gasoline that fuels our cars. Without it, our metabolism grinds to a halt, and our cells rapidly die. In order to achieve and maintain an attractive physique, low body fat, and an overall healthy body it is necessary to have an adequate supply of ATP. The more ATP we have available, the more efficient our cellular metabolism will be, and consequently the aging process slows. The number and density of mitochondria is not fixed throughout life. Exercise is the most proven method to improve the function of your existing mitochondria and to stimulate the production of additional mitochondria (called mitochondrial biogenesis), which in turn provides even more ATP for your cells. Activating sirtuin genes through calorie restriction or resveratrol mimics the exercise effect on mitochondria. Although creating ATP is essential to life, reactive oxygen species (ROS) or free radicals can and do form during this process, and are potentially harmful if they are produced in excess.[6] Cells have several antioxidant systems to counteract the potentially harmful effects of ROS. However, when the over production of ROS exceeds the capability to remove them, oxidative stress ensues, as it is frequently encountered in obesity, aging and many disease states. The degree of oxidative stress impairs stem cell function and influences the rate of telomere attrition; that is, the rate that telomeres shorten. This is a case where length really does matter.
Telomeres are end-caps on your chromosomes that protect the integrity of the genetic material (see “Start Growing Younger”). Telomeres shorten with each cell division. In fact, you can judge the age of a cell by measuring telomere length. When the telomere gets sufficiently short, the cell enters a state of senescence and sometime dies. So the telomere serves as a molecular counter, or clock, for the cell. But the telomere does more than just tell time. As the telomere shortens, it changes the behavior of the cell and makes the chromosome more susceptible to mutations; the very type of mutation that can lead to cancer. Cells with shorter telomeres begin to slow down. The signals that control hormone output and immune function become weaker. They start to act old. We all are well aware that our bodies function less optimally and the incidence of chronic diseases and cancer are more common as we get older. That is, unless we take an active role in preserving our health; which comes down to preserving mitochondrial function and telomere length.
Regularly, new studies are published demonstrating the correlation between telomere length and health. In a recent analysis of a subset of the National Long Term Care Survey, telomere length was associated with disability, functional status, cardiovascular disease and cancer.[7] A recent study found a correlation between telomere length and years of healthy life.[8] An intriguing connection has also been observed between telomere length and levels of psychological stress.[9] This is particularly relevant since individuals subject to chronic psychological stress show a shortened lifespan and more rapid onset of diseases typically associated with aging. Researchers in Italy recently found a direct association with short telomeres and an increased risk of developing and dying from cancer. The risk of dying was eleven times higher in those with the shortest telomeres.[10]
So what can be done to age more youthfully? Well, there is no magic bullet. Regular exercise increases mitochondrial function, stimulates mitochondrial biogenesis and has been shown to upregulate telomerase, thereby increasing telomere reserves. Exercise also reduces stress, improves mood and when combined with a healthy plant-based diet improves telomere maintenance.[11] Obesity is associated with shorter telomeres and an increased risk of several degenerative diseases. Reducing body fat also improves mitochondrial energy production.
How the various pathways are interconnected still remains to be conclusively determined. Mitochondrial dysfunction and an inability to generate adequate amounts of ATP may be the underpinning of the frailty associated with aging. Intact mitochondria are also crucial for the maintenance of stem cells for tissue regeneration. But, there is compelling evidence from the study of a wide range of human degenerative diseases pointing to telomere length as the key element driving degenerative pathologies, increasing cancer risk and shortening lifespan.[12]
How long are your telomeres? Telomere length testing is available at Alternity Healthcare. 860-561-2294
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