The Definition of Regenerative Medicine Includes the Treatment and Reversal of Aging

The staff at the SENS Research Foundation, who coordinate and carry out scientific programs aimed at speeding up progress towards rejuvenation therapies, have for some years referred to their work as a branch of regenerative medicine. When most people think of regenerative medicine, stem cell therapies to treat injuries and age-related diseases are the first thing to spring to mind, but that is just the most visible, energetic, and highly funded part of a much broader field. Wherever there is loss or degeneration in our physiology, a treatment that can even partially reverse that state of affairs, restoring some fraction of normal function to tissues, can reasonably be called a regenerative therapy.

Aging is defined by degeneration and failure. The most straightforward definition and measure of aging is that your risk of death due to intrinsic causes rises over time. Those intrinsic causes are the slow accumulation of molecular damage as a side-effect of the normal operation of cellular metabolism, and a resulting loss of function and resilience in damaged organs and systems. To pick one example, degeneration of the heart and cardiovascular system means an ever greater risk of abrupt failure and consequent death, and that degeneration can be traced back to root causes ranging from cross-links in the extracellular matrix that stiffen arteries, leading to high blood pressure and all of its unpleasant consequences, to growing numbers of senescent cells that produce inflammation and all sorts of other tissue damage, to increasing quiescence and lower rates of activity on the part of the stem cells that maintain heart and blood vessel tissues. These are degenerative changes, marked by decline. Just as delivering stem cells as a therapy can somewhat reverse the loss of tissue maintenance, a way to turn back the clock a little on some of the consequences of that issue, clearing cross-links or senescent cells will help in similar ways. These are all early forms of induced regeneration.

The article linked below skips from one end of the longevity science community, SENS rejuvenation research, to the other, attempts to modestly slow aging with existing drugs. I'm very much more in favor of the former than the latter: the costs are lower and the potential gains far larger. In the middle there is a look at regenerative medicine in the sense of cell therapies and their infrastructure, but it is interesting to see that more people are picking up on the unification of medicine now that the treatment of aging is a realistic prospect for the near future. Aging is not stuck out on the edge on its own, as something somehow out of bounds or different from the treatment of age-related disease. It is all a part of the same tapestry, and the more focus put on aging, the more likely that real progress will be made in bringing the clearly identified causes of aging under medical control.

Regenerative Medicine Comes of Age

Induced pluripotent stem cells (iPSCs) and genome-editing techniques have facilitated manipulation of living organisms in innumerable ways at the cellular and genetic levels, respectively, and will underpin many aspects of regenerative medicine as it continues to evolve. An attitudinal change is also occurring. Experts in regenerative medicine have increasingly begun to embrace the view that comprehensively repairing the damage of aging is a practical and feasible goal. A notable proponent of this view is Aubrey de Grey, Ph.D., a biomedical gerontologist who has pioneered an regenerative medicine approach called Strategies for Engineered Negligible Senescence (SENS). He works to "develop, promote, and ensure widespread access to regenerative medicine solutions to the disabilities and diseases of aging" as CSO and co-founder of the SENS Research Foundation. He is also the editor-in-chief of Rejuvenation Research, published by Mary Ann Liebert.

Dr. de Grey points out that stem cell treatments for age-related conditions such as Parkinson's are already in clinical trials, and immune therapies to remove molecular waste products in the extracellular space, such as amyloid in Alzheimer's, have succeeded in such trials. Recently, there has been progress in animal models in removing toxic cells that the body is failing to kill. The most encouraging work is in cancer immunotherapy, which is rapidly advancing after decades in the doldrums. Many damage-repair strategies are at an early stage of research. Although these strategies look promising, they are handicapped by a lack of funding. If that does not change soon, the scientific community is at risk of failing to capitalize on the relevant technological advances.

For decades, an urge to discern the secrets of unusually long-lived people has animated the work of Nir Barzilai, M.D., a researcher who is currently the director of the Institute for Aging Research at Albert Einstein College of Medicine. The Targeting Aging with MEtformin (TAME) study is focused on the concept that multimorbidities of aging can be delayed by metformin, a commonly used drug for the prevention and treatment of type 2 diabetes. Studies have demonstrated a decreased risk of not only cardiovascular disease but also cancer risk and cancer mortality in type 2 diabetic individuals taking metformin.

The TAME study hypothesis is that delaying aging is the only effective way to delay age-related diseases and compress morbidity. Sponsored by the American Federation for Aging Research, the study will recruit elderly subjects and, in a double-blind, placebo-control study, will test if metformin can put off the onset of multimorbidities including cancer, cardiovascular disease, type 2 diabetes, cognitive decline, and mortality. As the study's principal investigator, Dr. Barzilai hopes to convince the FDA to approve aging, as measured by multiple disease endpoints, as an indication. There is a great benefit for healthy lifespan, not only to the individual, but also for society in the form of cost savings, which is often referred to as the longevity dividend.


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