Fight Aging!

One of the challenges inherent in talking to the public about aging is that there are many well-popularized rare conditions that have the superficial appearance of accelerated aging or slowed aging, but are in fact nothing of the sort. Take progeria, for example: it is a comparatively simple genetic dysfunction that induces a great deal of cellular dysfunction and damage. Aging itself is a matter of specific forms of cellular dysfunction and damage, but any vaguely similar limiting of cell activities will produce some of the same outcomes, such as failure of tissue maintenance and a decline in organ function and integrity. Progeria patients die young from cardiovascular disease as a result of these issues, and appear prematurely aged. Yet the type of damage to cells that occurs in progeria has next to no role in normal aging, and vice versa, and the outcomes only appear similar at the large scale because the essential high level functions of tissue are disrupted in both cases. In fact the two conditions, progeria and aging, have nothing to do with one another, and it is probably the case that little learned in progeria research will be applicable in the treatment of normal aging.

This is a moderately complex set of ideas to explain in enough detail for it all to make sense to someone not versed in the underlying science. It takes a little time, and good explanations are all too often obscured by simplified media stories that talk about accelerated aging in ways that make sound like progress in progeria research is a direct and useful approach to learning about normal aging. Not the case at all, however.

Another example of the type that has been making the rounds in the media for the past few years is a rare developmental disorder in which the child does not develop: one individual lived for two decades while remaining an infant. The colloquial sense of the word "aging" includes growing up to adulthood as well as getting old, and so the media breathlessly calls this arrested aging, but these are two quite different processes. The degeneration and loss of function in later aging is caused by accumulated damage that occurs as a side-effect of the normal operation of metabolism. The passage from childhood to adulthood is an evolved developmental program of growth and change. If that developmental program is broken, the individual will still age, will still accumulate cellular and tissue damage for so long as their metabolism is operating. It seems unlikely that there is anything of practical use for aging to be learned here, despite the hopes expressed by some of the people involved:

Epigenetic age analysis of children who seem to evade aging

We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions whose physical development was dramatically delayed resulting in her appearing to be a toddler or at best a preschooler, even unto the occasion of her death at the age of 20 years. The pediatrician who cared for her from birth described his patient's strange affliction, that did not fit any disease category, as an "unknown syndrome" later to be called "syndrome X". As the result of her persistent "toddler-like" appearance, she received extensive notoriety from the media, and was featured as the "girl who doesn't age" in press articles and television broadcasts.

While most of the individual defects she experienced are not uncommon in many children, it was her retaining toddler-like features while aging from birth to young adulthood that made the case particularly unusual. Even children with growth retardation or failure to thrive exhibit maturation of facial and other physical/functional features with passage of time, indicating that their developmental program is still functional. In contrast, the peculiar trait of the first case suggested that her rate of aging was dramatically delayed or even arrested. If so, then perhaps an etiological understanding of her pathology might lead to novel treatments for age related diseases.

The objectives of this study were two-fold. The first was to determine if other such cases of syndrome X actually exist and thus might represent a novel syndrome. Then, because the case's appearance remained that of a toddler despite the passage of time, our second objective was to determine if there was any evidence that the arrested development in such children is linked to a slowing down of aging at the molecular level.

We identified five new cases whose clinical presentations were similar to the first case. Thus, while extremely rare, the first case described was not unique in the world. Furthermore, since such children require extensive medical care to survive, especially during the first years after birth, it may be that most succumb before ever being diagnosed. All of the identified subjects were female. It is not known whether this occurrence was due to chance alone or is a sex linked aspect of the putative syndrome.

To objectively measure the age of blood tissue from these subjects, we used a highly accurate biomarker of aging known as "epigenetic clock" based on DNA methylation levels. Our results demonstrate that despite the clinical appearance of delayed maturation in children afflicted with syndrome X, the epigenetic clock indicates that the rate of development in blood and perhaps other tissues is normal. Thus, while we cannot exclude tissue-specific ageing as causal in syndrome X, the current findings suggest that the observed delay in whole body development results from other, yet undiscovered factors. Future studies should assess whether other tissue types from these subjects (or their bodies as a whole) evade epigenetic aging.