SENS Research Foundation Investigates Cell Loss

Each day, body cells withstand a constant onslaught of destructive forces that can damage cells.

Each day, body cells withstand a constant onslaught of destructive forces that can damage cells. The body will attempt to either repair or destroy damaged cells using a type of cellular suicide known as apoptosis. Sometimes the body cannot destroy damaged cells completely so it forces these cells into a state somewhere between living and dead called “senescence,” where they stop growing in order to avert the possibility of the damaged cells becoming cancerous.

In many tissues, the body tries to replace lost cells quickly with specialized, tissue-specific stem cells. Exercise can stimulate the division of specialized stem cells in muscle tissue, for example. This works well in young bodies but over time, the degenerative process of aging makes older stem cells less effective at repairing damaged cells. Additionally, some tissues are not equipped with such specialized stem cells: in such tissues, the cells a person has in early adulthood are all he or she has to last a lifetime.

This is especially significant when long-lived tissue, like that in the brain, heart and muscles begins to lose cells and the ability to function well. Decreased cell count and poor function in the brain causes neuron loss that contributes to cognitive decline, dementia, and loss of muscle coordination. Diminished cell count causes skeletal muscles to weaken and fail to respond to exercise. Cell loss in heart tissues results in poor cardiovascular function associated with old age and invites a host of cardiac conditions.

Nowhere, perhaps, is cell loss more devastating than in the thymus.

The thymus is a pyramid-shaped organ in the chest, located between the breastbone and the heart. Before birth, throughout childhood and into puberty, the thymus is instrumental in the production and maintenance of a specific type of white blood cell that protects the body from viruses and other threats. This white blood cell, known as T-lymphocytes or T cells, is essential to human immunity. It circulates around the body, searching for cellular abnormalities and infections.

The thymus begins to shrink after puberty, and its functional tissue is slowly replaced with fat. The organ slows T-cell production as it shrinks. This leaves the aging person increasingly vulnerable to infectious diseases, including influenza and pneumonia. Engineering a youthful thymus, therefore, would help restore a youth immune system.

Medical scientists hope to do exactly that — engineer and introduce youthful cells and tissue to restore health and vitality to aging organs. Today, surgeons already perform organ transplants and blood transfusions to treat illnesses such as kidney failure. Unfortunately, the number of healthy donor organs and the risk that the recipient’s body will reject the transplant limits the number of successful transplants doctors can perform.

The SENS Solution

Two emerging SENS technologies address cell loss and replacement problems, not just to reduce the risk for organ rejection but also to prevent or treat diseases associated with age-related cell loss. With these technologies, physicians will someday be able to use the patient’s own cells to create custom-made cells. This eliminates organ rejection and the need for donors.

Both technologies focus on turning adult cells into embryonic stem-like cells. In their natural form, embryonic stem cells have the ability to turn into any type of body cell. These cells would be free from any genetic defects caused by aging or environmental damage. There would be no chance for rejection because the cells come from the patient’s own body. Furthermore, the physician would be able to grow as many cells as he needs for therapeutic treatment.

The first technology involves various procedures that turn old cells into a state similar to an embryonic stem cell that is capable of turning into a different type of body cell. Using chemical cues, such cells can then be nudged to become the kind of cell that is needed, and used to rebuild and reinforce the aging tissue. A variation on this method involves taking advantage of the fact that in some cases, mature cells from a particular part of the body can be nudged directly to become other cell types in the same tissue, without having to first be reprogrammed all the way back into an embryonic-like state. Skin-like supporting cells in the heart, for example, can be nudged directly to make new heart muscle cells.

The second method for creating embryonic cells from adult cells is to infuse a donor egg with the genetic instructions from the recipient, to create embryonic stem-like cells that are built according to the recipient’s genetic instructions. Scientists would then take steps to encourage these embryonic-like cells to develop into the type of cell needed to provide therapy to the patient.

SENS Research Foundation funding is helping Dr. John Jackson’s lab at the Wake Forest University Institute for Regenerative Medicine investigate the potential to engineer a new thymus gland to restore a youthful and vital immune function.

SENS Research Foundation is also funding Dr. Graça Almeida-Porada’s work in engineering new intestinal tissue that would someday relieve inflammatory bowel disease or intestinal damage associated with radiation therapy for pelvic or abdominal cancer. This rejuvenated intestinal tissue reverses poor nutrient absorption and immune dysfunction associated with the aging intestine.

SENS Research Foundation continues to work towards reversing the detrimental effects of aging that cause widespread and unnecessary debilitation and misery among the older population. Their advances in preventing cell loss in vital organs can vastly improve the lives of the aging population that now inhabits planet earth.

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