Aging hypotheses are resumed into two categories:
1. first invokes extrinsic and intrinsic factors that damage intracellular or extra cellular molecular structures.
2. second invokes changes in gene expression that are either programmed or that are bought about by normal changes in DNA structure.
Do they overlap - it is not known yet. Caloric restriction is common phenomena how to increase lifespan in living species including animals. Optimal food restriction was 50-70% in range. Such CR extends the mean and maximum lifespan.
The way it works may be: by reducing oxidative stress and damage caused by reactive oxygen species. Lin et al. describe intriguing results that may link CR to the control of gene expression and to suppression of DNA damage caused by mitotic recombination. All experiments were carried on yeasts.
Yeast undergo only a finite number of divisions, after which they die; thus, their life-span is defined by the number of divisions each cell completes. Lin et al. induced CR in yeast by limiting glucose availability or by genetically crippling their ability to sense and respond to glucose. Caloric restriction extended yeast longevity by 20 to 40%, similar to the relative life-span extension induced by CR in mammals. Of importance, this extension required the yeast genes NPT1 and SIR2. NPT1 encodes one of two enzymes that produce NAD (nicotinamide adenine dinucleotide), a key intermediate in energy metabolism. SIR2 - one of four silent mRNA regulator genes - encodes a protein that promotes a compact chromatin structure, thereby silencing gene transcription at selected loci.
As noted by Lin et al., the yeast SIR2 protein (Sir2p) is an NAD-dependent histone deacetylase, an enzyme that removes acetyl groups from the lysine residues of histone proteins (which are components of chromatin). This suggests that, through histone deacetylation, Sir2p may silence genes. In addition, the NAD requirement of Sir2p may serve to link its activity to the energy status of the cell. Thus, Sir2p may coordinate energy status with gene expression. Moreover, because by compressing chromatin, Sir2p regulates the access of many nuclear proteins to the DNA. It represses homologous recombination at the highly repetitive ribosomal DNA (rDNA) locus.
The formation and accumulation of extrachromosomal rDNA circle molecules (and possibly other DNA fragments) is a major cause of yeast aging. These circle molecules are formed by homologous recombination during the cell cycle. Homologous recombination is important for repairing damaged DNA in yeast, but can inappropriately excise DNA fragments from regions of extensive homology, such as the rDNA locus. Sir2p modulates yeast life-span largely by suppressing rDNA circle formation and loss of rRNA genes from the chromosome. Lin et al. have discovered that CR also suppresses rDNA circle molecule formation. Thus, at least in yeast, CR may extend life-span by modulating Sir2p activity and hence gene expression and recombination at silenced loci. One can now envision a model whereby the inevitable production of reactive oxygen species compromises mitochondrial efficiency, and eventually energy output, in a detrimental feedback loop. NAD levels may reflect energy status and influence chromatin silencing through the NAD requirement of Sir2p. Caloric restriction may decrease the impact of reactive oxygen species, including their indirect effect on the decline in energy production. Thus, by reducing the impact of reactive oxygen species and the resulting decrease in Sir2p activity, CR may postpone loss of chromatin silencing. But how could loss of chromatin silencing lead to aging?
The state of chromatin is essential for maintaining optimal gene expression and for suppressing homologous recombination. Loss of chromatin silencing alters gene expression, which can compromise the cell’s ability to vitability, and possibly its ability to withstand stressful factors. In addition, increased recombination leads to the lethal accumulation of rDNA circles, and possibly other detrimental mutations. Life-span extension by CR delays but does not prevent aging in both yeast and mammals. Two processes - DNA replication and DNA repair - may alter chromatin silencing and recombination independently of Sir2p and NAD availability. In both processes, DNA is partly stripped, albeit transiently, of regulatory proteins, which must be rapidly reassembled. Mistakes or transient states in the reassembly process may leave chromatin susceptible to inappropriate transcription or recombination events. Because the probability of undergoing DNA replication and repair increases with the number of cell divisions, the probability of acquiring imperfectly silenced (or configured) chromatin will rise with age. Likewise, the probability that faulty DNA replication or error-prone repair will generate (or fix) mutations will rise with age. Thus, CR, or even perfect chromatin silencing, can postpone aging phenotypes, but cannot delay them indefinitely. This is consistent with the finding that CR reverses some, but not all, gene expression changes that accompany aging in rodents. How pertinent might this model be to mammals? History tells us that we can learn a great deal about human biology from model organisms. Therefore, we may expect that chromatin silencing, or chromatin maintenance in general, will play a role in the development of aging phenotypes in mammals. Indeed, silenced genes on human X chromosomes and other loci become reactivated with age, suggesting that age-related loss of silencing does occur in some mammalian cells. Moreover, preliminary studies suggest that CR will be effective in primates. Proteins such as Sir2p may well serve to link metabolism to chromatin state in mammals, including humans, although this idea has not yet been rigorously tested, even in yeast. However, owing to their complexity, mammals may engage multiple SIR2-like proteins, perhaps some that are tissue-specific. Finally, WRN, the gene responsible for Werner syndrome, a disease of premature aging in humans, is a member of a gene family that is likely to participate in recombination and other DNA repair pathways, suggesting that recombination and DNA repair may be important determinants of the rate of aging in mammals.
A fundamental difference between adult mammals and model organisms such as the yeast, the nematode, and the fruitfly is the prevalence of cancer in mammals, and essentially the lack of cancer in yeast, worms, and flies. In mammals, mutations, very likely coupled to the changes in cellular function that accompany aging, give rise to cancer, which poses an additional threat to longevity. In addition, most human cells undergo telomere attrition with successive cell divisions and aging (that is, the ends of chromosomes become progressively shorter). The extent to which telomere-induced cellular senescence contributes to human aging is not yet clear, nor is it known how telomere length contributes to the senescent phenotype of cells. In yeast, telomeres increase the compactness of nearby chromatin, but we do not yet know if this process occurs in human cells. It is intriguing, however, that telomere shortening occurs more rapidly on human X chromosomes, which could contribute to the age-dependent reactivation of X chromosome loci. The state of chromatin is now at the center of several processes known or suspected to be important in mammalian aging, suggesting, once again, that model organisms have served us well.
Uncategorized | 15.07.2008 21:05 | Comments Off
Blueberry muffins may have a whole new appeal. According to the U.S. Department of Agriculture (USDA) and University of Illinois researchers, numerous health benefits may stem from phytochemicals such as flavonoids including anthocyanins, substances that give blueberries their pigment.
Deep-blue Wild Blueberries may be “one of the best age-proofing foods in your diet,” according to James A. Joseph, Ph.D., co-author of The Color Code and lead researcher at the Jean Mayer USDA Human Nutrition Research Center on Aging.
In particular, USDA researcher Ronald Prior, Ph.D., has determined that blueberries have the highest antioxidant capacity of 40 tested fruits and vegetables, after determining their oxidative radical absorbance capacity — their ability to protect against free radical damage. The antioxidant activity seems to arise largely from the anthocyanins.
Dr. Ronald Prior, lead researcher at the USDA Arkansas Children’s Nutrition Center and Agricultural Research Service, found that a one-cup serving of Wild Blueberries had more total antioxidant capacity (TAC) than a serving of cranberries, strawberries, plums, raspberries and even cultivated blueberries. According to Dr. Prior, “Wild Blueberries are stars in terms of their antioxidant capacity.”
Scientists around the world are studying the wild blueberry and the many health benefits offered by this tiny blue fruit. The many potential health benefits of Wild Blueberries include:
• Brain Health: Ongoing brain research shows that blueberries may improve motor skills and actually reverse the short-term memory loss that comes with aging.
• Cancer Prevention: Research shows that blueberry compounds may inhibit all stages of cancer.
• Heart Health: Research indicates that blueberries may protect against heart disease and damage from stroke.
In addition, recent laboratory studies suggest blueberries may delay the onset of age-related loss of cognitive function such as diminished reasoning and memory skills, according to James Joseph, Ph.D., a USDA researcher at Tufts University in the Human Nutrition Research Center on Aging. Another recent study demonstrates that one of the blueberry’s flavonoid components may inhibit an enzyme involved in the promotion stage of cancer, according to Mary Ann Smith, Ph.D., at the University of Illinois. On all counts, further research is needed to confirm the results of these studies, but so far these delicious berries seem to promise a wealth of nutritional benefits.
Uncategorized | 15.07.2008 21:04 | Comments Off
Alternative names
age related macular degeneration, central retinal degeneration
Definition
The macula is the center of the retina at the back of the eye. The images we see are sent to the macula and the rest of the retina. The macula has been likened to the film of a camera, which stimulates the brain so that we “see” the image in our mind. When the macula breaks down in a condition known as macular degeneration, decreased vision results.
Potentially there are a lot of risk factors involved in macular degeneration. As treatment for macular degeneration is not always effective, preventing it becomes necessary. This prevention is possible only by determining some of the risk factors involved.
What is going on in the body?
The macula is the most critical portion of the retina. It is responsible for detailed vision. This function is necessary for reading and seeing distant objects in detail. When the macula breaks down or becomes damaged, vision is affected. Most of the time, this breakdown is age-related. It can also occur in younger people who have a genetic tendency toward the condition.
What are the signs and symptoms of the disease?
Activities such as threading a needle, reading, seeing road signs at a distance, or recognizing individuals across the room may become difficult or impossible. Macular degeneration reduces vision in the center but does not affect the eye’s peripheral or side vision. This means a person will be able to see large objects well. For example, a person may be able to see the outline of a clock but may not be able to tell what time it is. People with this problem may see objects as smaller or larger than they really are. For some people, the condition causes a dark or empty area in the center of the field of vision. For others, straight lines look distorted and vertical or horizontal structures may appear to have a “pucker” in them.
This condition does not result in total blindness. Most people continue to have some useful vision. They are able to take care of themselves until the disease is very advanced. Also, vision is sometimes reduced in only one eye. The other eye may be able to see well for many years. When both eyes are affected, the individual will notice the problem more quickly.
What are the causes and risks of the disease?
# Most of the time, macular degeneration occurs as part of the normal aging. It is more common in people with certain risk factors. These include: female gender
# smoking
# high blood pressure
# Caucasian race
Obesity- According to recent studies there is an association with body mass index, waist circumference, and waist-hip ratio to the progression of age-related macular degeneration. Overall and abdominal obesity increases the risk for progression to advanced AMD, but more physical activity tends to decrease the risk.
For younger people, there may be a genetic link. This is especially true if there is a strong family history of the condition. More women as to compared men have MD and it may be due to the fact that women tend to live longer. Other risk factors include high blood pressure, cardiovascular disease and Alzheimer’s disease, among other causes.
# There are two common types of age-related macular degeneration. The dry or atrophic type is caused by the gradual thinning of the macula and the loss of pigment in this area. This is due to aging. Even though the degree of damage caused by macular degeneration varies from person to person, there are 2 broad categories of macular degeneration.
# The wet or exudative form of the condition accounts only for about 10% of cases. It occurs when tiny, abnormal blood vessels form under the retina. These vessels leak fluid or blood. This can cause blurring of the central vision. When this occurs, vision loss may be rapid and severe.
What can be done to prevent the disease?
Unfortunately, macular degeneration is not well understood and there are no known prevention methods. Some studies have shown that certain vitamins and minerals, such as vitamin E, vitamin C, and zinc, may slightly decrease the risk of developing this condition, but their effectiveness has not been proven. Avoidance of smoking may possibly lower a person’s risk. Wet macular degeneration accounts for only about 10% of the total cases. Wet macular degeneration is also called as choroidal neovascularization, subretinal neovascularization, exudative or disciform degeneration.
How is the disease diagnosed?
Often, no symptoms are evident until the breakdown of the macula causes blurred vision. An eye doctor can detect the problem by dilating the person’s pupil and looking at the back of the eye. In another test, individuals will look at a grid resembling graph paper. This is called an Amsler grid. If some of the lines appear lost or distorted, a problem with the retina exists.
Also, special photographs of the back of the eye may be done to reveal abnormal vessels under the retina. For this procedure, a fluorescent dye is injected into a vein in the arm. Rapid sequence pictures are then taken. This is called a fluorescein angiogram.
What are the long-term effects?
With the dry form of the condition, central vision is gradually reduced over many years. Sometimes the condition will be stable for a number of years without worsening. In the wet type of macular degeneration, vision may decrease suddenly. If this happens in one eye, the other eye should be carefully monitored.
There is a marked loss of central vision in advanced macular degeneration. People tend to become frustrated with their condition. They are unable to drive, cannot read without bright light and magnification, and cannot recognize friends from a distance.
What are the treatments?
# Despite ongoing research, there is no cure for the dry form of macular degeneration at this time. Findings from recent studies suggest that anti-oxidant vitamins and minerals may slow the progress of the condition. At present, this form of the disease is managed by helping the person cope with the condition. Optical devices can sometimes be used to take advantage of a person’s side vision. Low vision aids can also help affected individuals. These include: magnifying devices
# closed circuit television
# large print reading materials
# talking or computerized devices
The wet type of macular degeneration can sometimes be treated with laser surgery. This is an option for only about 25% of people with the condition. It is a brief and painless outpatient procedure. A laser beam is used to seal the leaking blood vessels that are damaging the macula. This leaves a small permanent scar or blind spot at the point of laser contact. However, more sight is preserved overall. Another promising procedure is still in the investigational stage. It involves injecting a substance into the veins that circulates to the abnormal retinal vessels. These blood vessels are then exposed to a specific wavelength of light. The result is the formation of scar tissue that shrinks the vessels before they have had a chance to leak and obscure vision.
How is the disease monitored?
People with macular degeneration can check their vision daily by using an Amsler grid. This will reveal any sudden changes in either eye. An individual should test each eye separately. If the lines on the graph appear more wavy, blurred, or dark than before, then he or she should contact the eye doctor immediately. The grid can be taped to a refrigerator or bathroom mirror to make it easily available.
Uncategorized | 15.07.2008 21:03 | Comments Off