The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

PREFACE
What makes us age at the rate we do? More to the point: Why doesn’t
someone find out?
We now know a great deal about what human aging comprises, not
only in macroscopic terms but also at the molecular level. We also have a
respectable grasp of how these degenerative molecular changes interact.
What is missing is a similarly detailed understanding of what — again, at
the molecular level — is the process determining the rates of these changes.
We do not even know whether one determinant of those rates is dominant
or whether there are many factors with comparable influence. The layman
may reasonably ask why, given such spectacular advances in so many areas
of medicine, so little progress has been made on this most fundamental
health hazard. For the biologist it is, frankly, somewhat embarrassing.
This book presents and discusses the hypothesis that the rate of
accumulation of spontaneous mutations in our mitochondrial DNA is
the principal determinant of the rate of human aging. This is a school of
thought which has been developed over a period of 45 years and has
incorporated ideas from a huge range of biological specialisations. It is
still only a hypothesis, but recent advances in many of these contributory
disciplines have strengthened it very greatly, so that it has gained the
support of large numbers of professional gerontologists. Moreover, these
advances have made it much more detailed and concrete, and
correspondingly more readily testable; this is engendering a widespread
feeling that the “wilderness years” of gerontology are drawing to a close
and that progress towards a true causal understanding of aging will
henceforth be rapid. What is a “true causal understanding” of a process?
In my view it is best defined as a degree of knowledge that enables us to
influence the process as we wish.
The book is organised broadly into four parts. The four chapters
that follow the Introduction are devoted to background material, covering
(respectively) mitochondria, free radicals, lipid metabolism and the major
pathological features of human aging. Chapters 6 to 9 are essentially
chronological, describing the development of the theory, with emphasis
on recent advances in Chapters 8 and 9. Chapters 10 to 12 cover a wide
range of its potential predictions; those in Chapters 10 and 11 concern
compatibility with existing data, whereas Chapter 12 discusses
still-available tests. Finally, Chapters 13 to 17 discuss the medium-term
potential, contingent on the correctness of the hypothesis presented thus
far, for the development of therapies which would greatly increase the
healthy human lifespan.