Wednesday, July 2, 2014

Wrinkling and Sagging are Chronic Toxic Processes Not Directly Caused by Aging

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

Chapter 4 tackles the subject of human aging. Much of what we know about the aging process comes from studying rare diseases of premature aging, such as Hutchinson–Gilford progeria syndrome, Bloom syndrome, Werner syndrome, Cockayne syndrome, dyskeratosis congenita, Fanconi anemia, Wolfram syndrome, and xeroderma pigmentosum. The relationship between a these premature aging syndromes and natural aging processes are discussed in Chapter 4. The chapter synthesizes an approach to understanding aging gained by understanding the biological pathways that lead to cell death and degeneration in non-dividing cell populations.

Here is an excerpt from Chapter 4,
4.1.1 Rule—We do not have a scientifically meaningful definition for the diseases of aging. Brief Rationale—We do not know the cellular basis of aging; hence, we cannot determine whether a disease qualifies as a disease of aging on a cellular basis.
The majority of the so-called diseases of aging are conditions that make individuals look like old persons, or they are conditions that happen to occur more often in elderly individuals than in young individuals. One of the few points that experts in the field of aging can agree on is that the aging process is complex; not caused by any single factor.
4.1.2 Rule—Aging is not caused by a single gene. Brief Rationale—If aging were caused by a single gene, you would expect rare occurrences of loss-of-function mutations of the gene, leading to instances of human immortality. Outside of science fiction, immortal humans do not exist.
Most of us gauge aging by looking for visible features that always seem to be present in older individuals, and that are absent in youth. For the most part, these signs have very little to do with the biological aging process. The most familiar example is wrinkling and sagging. Wrinkling is a condition producedby chronic exposure to ultraviolet (UV) light. Over time, UV light denatures the connective tissue in the dermis, producing a condition called senile elastosis or, more accurately, solar elastosis. Most of the skin changes associated with aging, such as cracking, leathery texture, and poor elasticity (i.e., the ability of skin to regain its flat, tight surface after being stretched or pinched), are the result of chronic UV toxicity.

The other obvious change observed in older individuals is skin sagging. In many individuals, this is most pronounced in the folds of skin that grow under the chin and down the neck. Sagging flesh on older individuals is due entirely to two phenomena. The first is skin growth; humans grow their skin throughout life. This skin accumulates to different degrees in different individuals, depending on their genetically determined propensities for skin growth.

The other phenomenon is gravity. Without the effects of gravity, our skin would grow evenly over our body contours. We develop pendulous skin at sites with the least skeletal support (e.g., under chin, under breasts, under our arms). The changes we see in the skin of older individuals are due to the chronic effects of UV light, skin growth throughout life, and gravity that occur over time. They are not fundamental features of biological aging, because they do not occur in the absence of toxic conditions.

Is there any evidence to support this claim? One piece of evidence lies in differences in skin damage among races. The heavily pigmented races have much less wrinkling than the less pigmented races, because they are better shielded from UV light. Yet there is no corresponding extension of life expectancy among the less-wrinkled races, suggesting that damaged skin is unrelated to the aging process. Aside from that, any elderly person can do a simple experiment that will doubtless settle the issue for them. Strip off your clothes and inspect the parts of your body that are not exposed to light and that are not hanging from an anatomic prominence. For some, this would be the lower back or the upper thigh. In almost every case, you will be gratified to learn that this region of skin is unwrinkled, youthfully elastotic (i.e., will snap back in place when pinched), and relatively flat. Aside from a bit of softness due to skin growth, there really is not much difference between these protected regions of skin in elderly individuals and in young individuals. At this point, you can put your clothes back on, if you wish.

If wrinkling and sagging are not part of the aging process, then what physiological processes characterize aging?
As with every common disease, the biological basis of human aging is best understood by examining rare diseases that involve the aging process.

I urge you to read more about this book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D. tags: rare disease, common disease, disease complexity, complex diseases, genetics of disease, monogenic disease, polygenic disease, orphan disease, orphan drugs,