Search

Introduction: Longevity research has matured to the point where significantly postponing age-related decline in physical and mental function is now achievable in the laboratory and foreseeable in the clinic. The most promising strategies involve rejuvenation, i.e. reducing biological age, not merely slowing its progression., Areas Covered: We discuss therapeutic strategies for rejuvenation and results achieved thus far, with a focus on in vivo studies. We discuss the implications of interventions which act on mean or maximum lifespan and those showing effects in accelerated disease models. While the focus is on work conducted in mice, we also highlight notable insights in the field from studies in other model organisms., Expert Opinion: Rejuvenation was originally proposed as easier than slowing aging because it targets initially inert changes to tissue structure and composition, rather than trying to disentangle processes that both create aging damage and maintain life. While recent studies support this hypothesis, a true test requires a panel of rejuvenation interventions targeting multiple damage categories simultaneously. Considerations of cost, profitability, and academic significance have dampened enthusiasm for such work, but it is vital. Now is the time for the field to take this key step toward the medical control of aging.

Growing evidence supports the antagonistic pleiotropy theory of mammalian aging. Accordingly, changes in gene expression following the pluripotency transition, and subsequent transitions such as the embryonic-fetal transition, while providing tumor suppressive and antiviral survival benefits also result in a loss of regenerative potential leading to age-related fibrosis and degenerative diseases. However, reprogramming somatic cells to pluripotency demonstrates the possibility of restoring telomerase and embryonic regeneration pathways and thus reversing the age-related decline in regenerative capacity. A unified model of aging and loss of regenerative potential is emerging that may ultimately be translated into new therapeutic approaches for establishing induced tissue regeneration and modulation of the embryo-onco phenotype of cancer.

n/a.

In the 60 years since Medawar questioned the assumption that aging is a selected trait with a fitness benefit, mainstream biogerontology has overwhelmingly adopted the view that aging is a product of evolutionary neglect rather than evolutionary intent. Recently, however, this question has come to merit further scrutiny, for three reasons: a variety of new ways in which aging could indeed be "programmed" have been proposed, several phenomena with superficial similarities to programmed aging have been suggested to offer evidence for it and against the mainstream consensus, and above all it has become appreciated that the existence or otherwise of "pro-aging genes" has enormous implications for determining our optimal strategy for the medical postponement of age-related ill-health. Accordingly, it is timely to revisit the arguments and data on this topic. In this article I discuss difficulties in reconciling the programmed-aging concept with existing data, flaws in various arguments given by others that existing data prove aging to be programmed, and extensions of these considerations to various phenomena that in one or another way resemble programmed aging. I conclude that, however much we might wish that aging were programmed and thus that the ill-health of old age could be greatly postponed just by disabling some aspect of our genetic makeup, the unfortunate truth is that no such program exists, and thus that our only option for substantial extension of healthspan is a divide-and-conquer panel of interventions to repair the damage that the body inflicts upon itself throughout life as side-effects of its normal operation. I explicitly avoid arguments that rely on unnecessarily abstruse evolutionary theory, in order to render my line of reasoning accessible to the broadest possible audience.

Elsewhere in this issue, Marios Kyriazis articulates a sharply skeptical assessment of the feasibility of medical rejuvenation, otherwise known as the "damage repair" approach to postponing the ill health of old age. His critique incorporates many errors of fact and/or interpretation and/or logic, which I enumerate here. I recognize that many of these errors are by no means Kyriazis's alone but are shared by numerous observers across the full range of biological expertise. It is for that reason above all that I hope this exchange will be of value to readers. Additionally, Kyriazis raises a number of valid concerns that have not been systematically addressed, by myself or by others, in past publications; I will attempt to remedy that here. For clarity, I will not structure this response as an essay, but instead as a simple point-by-point list of comments concerning individual statements and inferences that Kyriazis makes.

One of the main benefits of the dramatic technological progress over the last two centuries is the enormous increase in human life expectancy, which has now reached record highs. After conquering most childhood diseases and a fair fraction of the diseases that plague adulthood, medical technology is now mainly preoccupied by age-related disorders. Further progress is dependent on circumventing the traditional medical focus on individual diseases and instead targeting aging as a whole as the ultimate cause of the health problems that affect humankind at old age. In principle, a major effort to control the gradual accumulation of molecular and cellular damage - considered by many as the ultimate cause of intrinsic aging - may rapidly lead to interventions for regenerating aged and worn-out tissues and organs. While considered impossible by many, there really is no reason to reject this as scientifically implausible. However, as we posit, it is not only scientific progress that is currently a limiting factor, but societal factors that hinder and may ultimately prevent further progress in testing and adopting the many possible interventions to cure aging., (© 2014 S. Karger AG, Basel.)

In their article in this issue, Olshansky and Carnes [Gerontology 2013;59:85-92] spell out in perhaps the most explicit terms yet a view which they have long espoused: that increases in longevity will inevitably slow down in decades to come, since the rate of biomedical progress that everyone agrees would be necessary to avoid such a slowdown is far too dramatic to be plausible. By doing so, they also betray more explicitly than ever before the flaws in their own logic. It is ironic that these flaws, unlike the work they critique, are actually quite closely analogous to the flaws in Zeno's paradox. Since others are offering their own comments on other parts of the article, I shall restrict my remarks on the article to those passages which refer specifically to my own work, together with the conclusion., (Copyright © 2012 S. Karger AG, Basel.)