In this piece at the MIT Technology Review, Aubrey de Grey of the SENS Research Foundation summarizes the strategy of rejuvenation research based on periodic repair of the cell and tissue damage that causes aging. This is a philosophy of development that has proven its utility over the past fifteen years, and especially recently with the growing data on senolytic therapies that remove senescent cells. Clearance of senescent cells was specifically called out by de Grey in his position paper in 2002, and he and his allies have advocated for it and supported it with research funding where possible since then. SENS, the Strategies for Engineered Negligible Senescence, is an assembly of all that is known of the root causes of aging, coupled with potential means to reverse or bypass them. If all portions of SENS were supported to the same degree as other lines of research into aging, then rejuvenation could be a near future reality.
There is a little history here regarding the venue. The editor of the MIT Technology Review was, back in the day, quite opposed to SENS and spent some effort attempting to find researchers willing to tear it down in public. This led to the SENS Challenge in which a prize was offered to people for success in proving SENS wrong. That came to the expected result, as SENS back then was, as it is now, based on a very large body of research and data, yet a decade ago the culture of science and the popular culture was inclined to dismiss out of hand anyone who talked rationally about treating aging as a medical condition. SENS was correct back then, and it is correct today; the only difference is that a great deal of work has taken place in the intervening years to persuade the scientific community and the world at large that, yes, building therapies to address aging is plausible, practical, and possible. The culture of aging research and the public perception of this research is now very different.
Since the dawn of medicine, aging has been doctors' foremost challenge. Three unsuccessful approaches to conquering it have failed: treating components of age-related ill health as curable diseases, extrapolating from differences between species in the rate of aging, and emulating the life extension that famine elicits in short-lived species. SENS Research Foundation is spearheading the fourth age of anti-aging research: the repair of age-related damage, that is, rejuvenation biotechnology. The Strategies for Engineered Negligible Senescence (SENS) approach was first proposed in 2002; we seek methods to convert a population experiencing a non-negligible level of senescence into one experiencing a negligible level.
To see how the goal of negligible senescence could be "engineered," it is useful to consider a situation in which human ingenuity and perseverance has already achieved an analogous result. Motor vehicles experience a process of wear-and-tear essentially similar to organismal aging; the paint flakes, windowpanes chip, rust infiltrates the pipework, and so forth. Nonetheless, as vintage car owners will attest, it is entirely possible to keep one functional for an essentially indefinite period. Critically, this is achieved not by preventing the wear but by repairing the damage that does occur at a rate sufficient to ensure that the function of the machine is never irretrievably compromised.
Aging can be characterized as a three-stage process. In the first stage, metabolic processes essential to life produce toxins. Secondly, a small amount of the damage caused by these toxins cannot be removed by the body's endogenous repair systems, and consequently accumulates over time. In the third stage, the accumulation of damage drives age-related pathology. This model - metabolism causes damage causes pathology - allows us to clarify the requirements for successful intervention in aging. Unlike the dynamic processes of metabolism and pathology, accumulated damage represents a relatively stationary target. That is to say, it may not be clear whether a given type of damage is pathological (on balance), but its absence from healthy twenty-year-olds indicates that it is not required for healthy life. Conversely it is clear that the total ensemble of types of damage in a fifty-year-old is pathological.
Accepting the implications of this model leads us to the SENS approach; by identifying and repairing all of the damage accumulated during aging, we can restore the body to a youthful state. Consequently, its dynamic metabolic processes will revert to their own norms, and the risk of mortality will be no higher than in any other equivalently "youthful" individual - whether they have actually lived for twenty years or 120. Furthermore - so long as our inventory of damage classes is sufficiently comprehensive - we can repeat this effort on a regular basis, and thus remain indefinitely below the threshold of pathology.
SENS is a hugely radical departure from prior themes of biomedical gerontology, involving the bona fide reversal of aging rather than its mere retardation. By virtue of a painstaking process of mutual education between the fields of biogerontology and regenerative medicine, it has now risen to the status of an acknowledged viable option for the eventual medical control of aging and its credibility will continue to rise as the underlying technology of regenerative medicine progresses.