RepleniSENS: Replacing lost cells
Every day, our cells are damaged by both tiny molecular-level insults and by obvious trauma. Some of these damaged cells are repaired, but others are either destroyed, or forced into a dysfunctional ‘senescent’ state where they can no longer divide, or commit ‘cellular suicide’ (apoptosis) for the greater good of the body. Some of the lost cells are replaced by the pools of specialized, tissue-specific stem cells, but the degenerative aging process makes these stem cell pools less effective at repair over time. The net result is that over the course of many decades, long-lived tissues like your brain, heart, and skeletal muscles begin to progressively lose cells, and their function becomes increasingly compromised. Muscles weaken, and don’t respond properly to exercise or injury. The brain loses neurons, contributing to cognitive decline and dementia, as well as to loss of control over fine muscle movements (a process that ends in Parkinson’s disease). The thymus – the gland in your breastbone where a major class of immune cells mature – shrinks, leaving you more vulnerable to infectious disease as fewer fresh immune cells are produced.
Cell division is naturally stimulated in some muscles by exercise, although most of the increased tissue volume and strength that results from exercise is a result of increasing the size of the exercised cells, rather than by actually recruiting new cells into the tissue. These processes can be artificially stimulated through the injection of anabolic steroids and other growth factors, but with side-effects, and without fully making up for the decay of the overall structure and function of the tissue. As well, stimulating cell division with growth factors comes with the risk of cancer. And the effectiveness of the body’s cell-replacement and healing processes are themselves impaired by the degenerative aging process, making exercise and growth factors less and less effective even as the tissues’ need for repair becomes increasingly critical.
The solution to this problem involves the rejuvenation biotechnologies with which most people are most familiar: cell therapy and tissue engineering, the science of growing organs for transplant in an artificial, biodegradable scaffold outside the body. The foundations of this form of medicine lie in the transplantation of organs and tissues that we already use to replace the blood of chemotherapy patients or the kidneys of dialysis patients. However, as most people know, the therapeutic potential of today’s lifesaving transplant-based therapies is severely limited by the limited number of organs and cells available for transplantation. As well, transplanting organs and tissues from one person into another can lead to terrible complications, when the immune system “rejects” and attacks the donated tissue as “foreign.” This immune reaction then needs to be suppressed by lifelong drug administration, impairing the recipient's resistance to infections and possibly to cancer.
Two emerging repleniSENS technologies will make these problems a thing of the past -- not only for patients with the kinds of diseases that are treated with transplanted organs and tissues today, but for restoring the health and vigor of the body with age, and for treating or preventing many diseases and disabilities caused by age-related cell loss. These technologies allow new cells and organs to be custom-made for the recipient from his or her own cells. This feature of these technique eliminates the need for others to donate cells and tissues, while also eliminating the fear of rejection. In both methods, scientists begin with mature cells (such as skin or blood cells) taken from the person who is in need of fresh cells or organs, and restore in them the lost powers of embryonic stem cells: to transform themselves into any kind of cell in the body, and to keep reproducing themselves inevitably.
The first method involves using various methods to deliver factors that “reprogram” these cells from the mature state into the embryonic stem-cell-like state, generating what are called “induced pluripotent stem cells.” A variation on this method allows scientists to take cells that are of a different kind from the cells that are needed, but present in the same tissue, and reprogram them into the needed cells without first passing through the embryonic-stem-cell-like state. For instance, such methods have been used to turn cells taken from the skin-like supporting tissues that knit around the heart muscle into needed heart muscle cells.
The second method of creating new embryonic-like cells from adult cells is to fuse an egg cell from a donor with cells from the person needing fresh cells, using the experimental technique of somatic cell nuclear transfer (or “therapeutic cloning”).
In both cases, one can give some of a person’s cells the embryonic-stem-cell-like ability to turn into any cell needed to treat age-related disease and disability, and to produce as many cells as are needed to do the job. Because these cells come from the same person who needs them, there is no risk of immune rejection. And whereas cells and organs donated from another person come with a significant burden of aging damage that accumulated while they were inside the donor, these new cells can be biologically “young,” free of any defects that are present in the native cells (such as mutations or other aging damage).
Scientists can then use biochemical cues to ‘nudge’ the cells to transform themselves into cells of the needed type: neurons for the brain, myocytes for the heart, and so on. They can also use the techniques of tissue engineering to build tissues and organs out of these cells.
In addition to replacing lost, dying, or dysfunctional cells, the ability to engineer new cells and tissues gives us an opportunity to use them as delivery systems for other rejuvenation biotechnologies. Additionally, there are several tissues in which specially-modified stem cells play an important role in the most likely strategy for defeating cancer.
Research Funded by SENS Research Foundation
RepleniSENS therapies are receiving far more research investment from government, other medical charities, and the biotech industry than any other rejuvenation biotechnology. SENS Research Foundation’s work in this area is therefore focused on projects that are not already receiving their share of support from these sources.
The thymus is a gland located at the top of the breastbone, where a class of immune cells called T-cells mature. The shrinking and structural decay of the thymus with age is one of the two main reasons (along with accumulations of defective cells) why we become increasingly vulnerable to influenza, pneumonia, and other infectious diseases as we age. Engineering healthy, youthful thymic tissue would help to restore the vigorous immune response of youth. At the Wake Forest University Institute for Regenerative Medicine, SENS Research Foundation funding is helping Dr. John Jackson’s lab step up research on engineering a new thymus gland, in order to restore youthful immune function.
Also at Wake Forest, SENS Research Foundation is funding Dr. Graça Almeida-Porada’s work in engineering new intestinal tissue. Tissue-engineered gut tissue for transplantation could be used to relieve the suffering of people with inflammatory bowel disease, or whose intestines have been damaged by radiation therapy during treatment for pelvic or abdominal cancer. As a rejuvenation biotechnology, new intestinal tissue will help to reverse the loss of nutrient absorption and immune function that occurs with aging in the intestine; it is also an important first step in the WILT strategy for defeating cancer.
For a more in-depth account of the importance of cell therapy and tissue engineering in ending the diseases and disabilities of aging, see the chapter “New Cells for Old” in Ending Aging, as well as the Afterword in the paperback edition.