Senescence-Based Diseases
"Resetting gene expression is the most efficient point of aging intervention; relengthening telomeres is the most efficient way to reset gene expression. ... The breadth of application of cell senescencence stems from its clinical implications for all age-related disease, reguardless of tissue. Its role in basic pathology suggests its depth of efficacy in treatment and prevention."
-- Michael Fossel
Cells, Aging, and Human Disease
Cardiovascular Disease
Cardiovascular disease is the leading cause of death world-wide. Many different types of failures in the cardiovascular system can lead to death but the most common failure is in the arterial vessels. We suspect that these arterial failures are a direct result of changes in the endothelial cells that line the vessel walls. By relengthening telomeres in endothelial cells we hope to be able to, not only address the underlying cause of cardiovascular disease, but also reverse the effect of age-related vascular damage.
Alzheimer's Disease
Many of us know someone who has suffered from the ravenges of Alzheimer's Disease, a degenerative disease of the brain. Most current research focuses on amyloid plaques and neurofibrillary tangles. Amyloid plaques are found outside the neurons, neurofibrillary plaques are found inside the neurons. Neuron cells do not divide at any significant rate so many people discount the role of telomere shortening in Alzheimer's disease and other dementias. However, neurons depend on glial and microglial cells for support, and these cells do divide continually. We hope that relengthening glial telomeres will address the underlying cause of neuronal damage, relieving the devastating effects of Alzheimer's disease.
Progeria
-- Hutchinson-Gilford Syndrome
-- Werner Syndrome
Progeria is a collection of syndromes all of which exhibit varying forms of premature aging. Progeria literally means early aging. The two most publicized forms of progeria are Hutchinson-Gilford syndrome, which strikes in early childhood, and Werner syndrome, which is an adult-onset disease. Children with Hutchinson-Gilford syndrome live an average of just under 13 years, dying primarily from atherosclerosis, usually cardiac or cardiovascular. People with Werner syndrome are usually diagnosed in their thirties and die in their forties. The progerias have been linked directly to premature telomere loss in a variety of cell types. We hope that by developing a drug to relengthening telomeres, we can finally provide an effective therapy for these currently incurable syndromes.
Osteoporosis & Osteoarthritus
Coming soon .
AIDS & Immunosenescence
When people become infected with the HIV virus their immune system springs into action to fight off the infection, but because HIV uses numerous effective strategies to elude the body's defenses, the immune system becomes depleted over time. We believe that CD8+ T-cells run out of replicative capacity allowing opportunistic infections to take hold once the body is defenseless. We hope that by relengthening the telomeres of these CD8+ cells the immune system will be able to fight off infection indefinitely.
We also hope the same strategy can be employed against other immunosenescent diseases, such as herpes zoster infections and influenza infections, as well as in age-related cases of compromised immune systems in the elderly.
Macular Degeneration
Macular degeneration results in the gradual loss of central vision, ultimately leading to blindness. Some evidence points to the senescence of retinal pigment epithelial cells as the cause of macular degeneration. We may be able to cure macular degeneration by lengthening telomeres in these cells. Similarly, the senescence of ocular keratocytes correlates with the development of cataracts and may be another target for a telomere relengthening drug.
Hepatic Cirrhosis
Cirrhosis causes may deaths each year and has no effective treatment. Liver cells normally turn over slowly and have excellent regenerative characteristics. In cirrhosis, however, regeneration is insufficient and abnormal leading ultimately to liver failure. While the damage incurred in cirrhosis may not be completely due to senescence, we believe relengthening telomeres in liver cells may delay or prevent loss of function and failure.
Skin
The skin is the largest organ of the body and our main defense against infection. Skin aging reduces our defenses and increases our chance of illness. Reducing age-related skin deterioration will not only make us look younger, but will also keep us healthier longer.
-- Wound Healing
Skin cells divide rapidly throughout our lifetimes and provide the most visible example of cell senescence-related damage. As skin cells lose their replicative capacity and the percentage of senescent cells begins to rise, a host of ills befall our skin. Older skin loses function. It produces less melanin, less collagen, less elastin. It becomes thin and tears easily. The number of glands diminishes, as do capillary beds leading to poor vascular regulation and support. As skin cells lose function our skin fails.
Experiments have shown that inserting telomerase into old skin cells returns them to a healthy youthful state, so much so that they cannot easily be distinguished from young cells. A drug that has the same effect may stem and reverse skin failure as we age. Such a drug would be valuable for treating decubitus ulcers, sepsis, hypothermic stress, and other conditions of poor wound healing. It could also be valuable in the production and use of skin grafts for severe burns and other conditions of traumatic skin loss.
-- Cosmetic Uses
In our opinion, despite the myriad anti-aging products currently on the market directed toward skin aging, there is nothing available anywhere that actually affects skin aging permanently. A skin cream containing a telomere-extending drug, however, applied topically, could slow or even reverse the deterioration of aging skin. We believe a product of this type may not only protect a person against age-related skin damage, but may also restore youthful resistance and appearance to the skin.
Bone Marrow Transplantation
Cells that are harvested from a patient or donor then induced to divide many times or genetically engineered before transplant into the patient, experience rapid telomere shortening and senescence, limiting their useful life span. Bone marrow cells lose approximately 40% of their replicative capacity during culturing. This problem becomes even more pronounced when the cells are first genetically engineered from a single cell using gene therapy procedures. By the time the cell population is sufficient for transplantation, the cells have gone through the equivalent of 50 years of aging. A telomerase inducing drug may eliminate the loss of replicative capacity, greatly extending their useful life span and effectiveness.
Monoclonal Antibodies
Monoclonal antibodies are proteins with the ability to specifically bind targets known as antigens. This binding specificity makes them potentially powerful therapeutic and diagnostic tools, able to block, trigger, or diagnose a particular biochemical or cytological function. The primary method of producing monoclonal antibodies requires the creation of immortalized antibody producing cells, called hybridomas, made by fusing B-lymphocytes (which secrete antibodies) with immortal (cancerous) myeloma cells to extend their life span. The fusion process can take from 8 to 12 months and represents approximately 25% of the cost of production. A telomerase inducing drug could be used to extend the life span of B-lymphocytes directly, reducing the production startup time to 2 to 3 months.
| Disease | Senescent Cell Type |
|---|---|
| Cardiovascular Disease | Endothelial Cells |
| Alzheimer's Disease | Glial Cells |
| Progeria | Multiple Cell Types |
| Osteoporosis | Osteoblasts |
| Osteoarthritus | Chondrocytes |
| AIDS & Immunosenescence | CD8+ T-Cells |
| Macular Degeneration | Retinal Pigment Epithelial Cells |
| Hepatic Cirrhosis | Hepatocytes |
| Skin Aging | Fibroblasts |
