Biological Fountain of Youth

March 27, 2015

By Medical Discovery News

The Biological Fountain of Youth

Over 500 years ago, Ponce de Leon landed in Florida as part of his search for the fountain of youth – magical waters that reverse aging, prevent illness, and grant immortality. He never found it, and neither has anyone else. While immortality is still impossible, we have come a long way in understanding the aging process.

We do not know the precise mechanism of aging, but there are some fundamental processes in our bodies that begin to change and this can drive aging. There are several theories of aging under intense scientific investigation.

A widely accepted theory of aging today is called evolutionary senescence, which mainly hinges on the concept of mutation accumulation. As we age, our cells accumulate mutations in our genetic material or DNA, which affects the ability of our cells to replicate and our tissues to regenerate. Also, some of our genes are designed to enhance reproduction early in life, but can cause problems later. Since genes can only be passed on during reproduction, which generally occurs earlier in life, genes that have negative effects later in life are not removed from the population – we are stuck with them! A good example is a gene called p53, which controls the fate of damaged cells by preventing their replication or directing them to die. This is important in preventing cancer in young people, but it may negatively impact our ability to replace aging cells in tissues as we grow older.

Another widely discussed theory centers on the maintenance of our genomes. As we get older, we accumulate damage to our DNA, which affects cellular function and our ability to renew tissues in the body. In a sense, this is a high mileage effect. Take for example the production of free radical molecules. These highly reactive molecules are normally produced in mitochondria, which use oxygen to produce cellular energy, a process that creates free radical molecules as a by-product. These free radical molecules lead to oxidative damage of DNA and other cellular components.

There is also evidence the neuroendocrine system (hormones that affect neurological function) influences aging. For example, a reduction in hormone levels can lead to a lengthening of life, at least in experimental animals. We are beginning to suspect that the insulin-related hormonal pathway may play a significant role in aging, at least in mice. Mutations that reduce the amount of this circulating hormone extend life.

A relatively new model of aging involves the replication of chromosomes as cells divide. When cells replicate, specialized structures at the ends of chromosomes called telomeres are shortened. Shortened telomeres are linked to decreased viability and increased cancer risk. Cells whose telomeres reach a critical length can no longer divide and are described as senescent.

We are expanding our understanding of how aging occurs. The search for a modern-day fountain of youth will require a great deal of dedicated work by biomedical scientists to safely improve and extend human life.

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When Two Parents Aren’t Enough

April 5, 2013

By Medical Discovery News

Ask expectant parents what kind of child they want, and one word almost always comes up: healthy. So, the possibility that a new baby may carry a genetic disorder can be understandably devastating. But a recent research from the Oregon Health Sciences Center may offer a unique approach to actually preventing certain types of genetic diseases – the three-parent child. 

When they invented this approach, researchers were thinking of the 4,000 children born each year with genetic defects in their mitochondrial DNA. These children consequentially develop one or more of 50 known mitochondrial diseases, many with devastating symptoms like stroke, epilepsy, dementia, blindness, deafness, and kidney or heart failure. Mitochondria are the power plants of the cell, producing the energy needed for a cell to function. Each mitochondrion has its own DNA independent and outside of a person’s DNA, which is housed in the cell’s nucleus. Diseases affecting mitochondria are difficult to treat, so this new way of actually preventing them is a welcome, while controversial, discovery.

First, eggs are obtained from the mother and a female donor. The nucleus from the egg of the natural mother is removed, separating her chromosomal genetic information from her mitochondria, which would have been passed on with the mutation to the child. This nucleus is then transferred to the donor egg, from which the nucleus and genetic information has been removed and discarded. The result is an egg with the nucleus and genes of the natural mother and the functioning mitochondria of the donor.

Then the egg is fertilized with the natural father’s sperm (which does not contribute any mitochondria to an egg), producing a fertilized egg with the DNA of the natural mother and father and the healthy mitochondrial DNA of the donor.  However, the contribution of the donor egg’s mitochondrial DNA is not much – the mitochondrial genome accounts for only 1 percent of the total DNA present in a human cell. So, the embryo will have genetic information from three people. The future child would share the genetic characteristics of the mother and father but have the mitochondrial genetic makeup of the egg donor.

In recent studies, scientists removed the nuclei and the DNA within from 65 human eggs and replaced them with donated nuclei. After fertilization, just under half of the eggs grew to a 100-cell stage called a blastocyst, the precursor to an embryo. This is the same rate seen for unaltered fertilized eggs. While the blastocysts were not implanted into wombs, they could have eventually developed into three-parent children. The change to their mitochondrial DNA could be permanent, and they could pass on the functional mitochondria to future generations. 

While this is huge progress for treating genetic disease, it also raises some significant ethical questions, such as whether the discovery could eventually be used to create “designer” babies, whose DNA has been manipulated to meet parents’ wishes. This technique holds great potential as an advance in genetic therapy, but its ensuing controversy means scientists should take steps to prevent abuses. 

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