What is the Fundamental Biological Process that Causes 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 explains that much what we think 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.

From Chapter 4:

Based on the observation that some of the premature aging diseases have defects in DNA repair, it was hypothesized that the longevity of animal species is determined by the species-specific rate of DNA repair. Species that had a high rate of DNA repair were expected to have a long lifespan. Species with low rates of DNA repair would be short lived. Though some data supported this hypothesis, a reanalysis of the data found little evidence to favor earlier conclusions[23].

In 2009, Walker and coworkers reported a case study of a sui generis condition observed in a 16-year-old girl who had the appearance and anthropometric traits of an 11-month infant [24]. External and internal organs were infantile, including brain structure. After fetal development and birth, she had failed to mature into early childhood or adolescence. In a sense, her condition is the opposite of the premature aging conditions. The extreme rarity of this condition (i.e., more rare than the very rare monogenic disorders that produce premature aging) suggests that a simple loss of function in a single gene is unlikely to be at fault. This strange and sad case raises many questions about human development and aging, but, at this time, there are no answers.

Though aging is a naturally occurring process, it is also a disease. It is a true disease, like any other disease, because it causes the decline of function in various organs; it leads to frailty and a reduced ability to cope with physiological stressors; and it leads inevitably to death. A disease that causes premature aging is a disease that produces all of the aforementioned features at an early age. When we examine diseases of premature aging, we find that the underlying mechanisms of these diseases are manifold: chromatin instability (Hutchinson– Gilford progeria); DNA instability (Werner syndrome); accumulation of toxic cellular products (tauopathies and prion diseases); mitochondrial degeneration (Wolfram syndrome); telomere shortening (dyskeratosis congenita).

What do all these syndromes of diverse etiology have in common? The answer to this question is the topic of the final sections of Chapter 4, from which excerpts will be selected for later blogs.

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, aging, ageing, DNA repair, biology of aging, orphan disease, orphan drugs, what causes aging?, what is the cause of aging?, diseases of aging, causes of aging, age-related diseases, the process of aging