Regardless of the in terpretation of the causes of aging, there is little debate th at excess free radicals are harm ful. Those partial to theories th a t the body is program m ed to age in a certain way argue that, while free radicals are clearly an expression of aging at the metabolic level, they alone cannot be a prim ary cause of it.
U nderstanding w h a t hap p en s to our bodies (as well as our m inds and spirits) as we age is not the sam e as know ing w h a t trig
gers the aging process itself. True, free radicals create big trouble, bu t w h a t allows th e m to do so m u c h more, say, at age sixty, as opposed to twenty-five?
For some, the answ er resides in the genes.
The logic behind program m ed theories of aging rests on the b e lief th at the body contains a genetic clock th at is preset by heredity to begin deteriorating at a given point and time. Central to such theories are results from anim al studies involving selected breeding
for extended life span and in vitro (outside the body) studies sh o w ing th a t certain cells stop replicating over time.
Variations on this them e have suggest th a t the heart has a lim ited n u m b e r of potential beats an d the im m u n e system generally reaches its greatest strength at puberty, only to gradually decline from th e n on. While the prospect of a ticking tim e bom b for self- destruction m ay bring little solace to the health-conscious individ
ual, there is clearly an elem ent of tru th to such thinking, in th a t all species have a m a x im u m life span and no one lives forever.
The concept of a n inn ate aging clock begs the question of w here it is.
Some have argued th a t it resides specifically in the m ito c h o n drial DNA. Others point to the h ypotham alm us, pituitary gland, th y m u s gland, or pineal gland. Yet it is the w ork of cell biologist Leonard Hayflick th a t is not only m ost responsible for m o d ern p ro gram m ed theories of aging, b u t has given rise to th e m ost intriguing idea to date.
In 1961, Hayflick found th at h u m a n cells, or fibroblasts, w hile continuing to live, only divide approxim ately fifty times before ceas
ing to function correctly. This finite n u m b e r has come to be k n o w n as the Hayflick limit. It is governed by three factors: The first is the m a x im u m life span of the species from w hich a cell is obtained.
Second involves the age of the cell's source, and the third depends on the type of cell itself. An obvious exception to such findings are cancer cells; they never stop dividing. Efforts to explain this ap p a r
ent contradiction spaw ned the telomere theory of aging. Developed in the early 1970s, it took hold in 1990 and rem ains a fertile area of research today.
Telomeres are the protective caps on the ends of chrom osom es th a t carry DNA. W ith few exceptions, there are forty-six ch ro m o somes on each cell. Every chrom osom e has two ends w ith a telomere on each one, w h ich adds up to 92 telomeres per cell. Studies show th a t a telomere is roughly 5,000 base pairs in length shortly after birth. It is shortened by roughly sixty-five base-pairs w ith each cell division. Because of this, some researchers argue th at the length of telomeres should be considered a biom arker of h u m a n cell aging.
They note th at cells stop dividing w h e n they get too short. This changes their gene expression and results in eventual cell death.
Advocates of the telomere theory suggest th a t by controlling the
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activity of telomeres, scientists m ay b oth be able to enable some cells critical to the aging process to keep replicating (th u s live longer) and prevent others (cancer cells) from doing so. In his book, Reversing Human Aging, Dr. Michael Fossel writes:
Cells have chromosomal "clocks” that determine their life spans.
A cell dies when its clock runs down. Cancer cells, on the other hand, continually reset their clocks, allowing themselves to divide forever. If we reset the clock of a normal cell, it lives anew; if we stop the clock of a cancer cell it dies. When we can set the clocks, your cells need not age and cancer can be cured.
It is Fossel's contention th a t all this m ay be possible w ith in the next ten years, a case he m ad e in the J u n e 3, 1998, issue of The Journal o f the American Medical Association. In an article entitled
"Telomerase and the Aging Cell: Implications for H u m a n H ealth,"
he notes th at "recent research has sh o w n th a t inserting a gene for the protein co m p o n en t of telom erase into aging h u m a n cells reex- tends their telomeres to lengths typical of young cells, and the cells th e n display all the o th er identifiable characteristics of young, health y cells."
Fossel argues th a t such findings no t only suggest th a t telomeres are the central tim ing m e c h a n ism for cellular aging, bu t also d e m o n strate th a t such a m ech an ism can be reset, extending their repli
cative life span, resulting in m arkers of gene expression typical of younger cells w ith o u t the hallm arks of m a lig n a n t transform ation.
Taking his case a step farther, he suggests, "It is now possible to explore the fu n d a m e n tal cellular m ech an ism s underlying h u m a n aging an d therefore d eterm ine the extent to w h ich the m ajor causes of d e a th and disability in aging populations in developed c o u n tries— cancer, atherosclerosis, osteoarthritis, m acular degeneration, and Alzheimer d e m e n tia — are attributable to such fu n d a m e n tal m echanism s. If they are am enable to prevention or tre a tm e n t by alteration of cellular aging, the clinical im plications have few h is
toric precedents."
Fossel's claims are bold, but he is not alone in m aking them . In a Jan u ary 16, 1998, article published in Science, A. G. Bodnar and colleagues reported on the results of a study in w hich two telo- m erase-negative norm al h u m a n cell types— retinal pigm ent e p ith e lial cells and foreskin fibroblasts— were transfected w ith vectors
encoding the h u m a n telomerase catalytic subunit. At the tim e of publication, the cells h ad exceeded the norm al life span by tw enty divisions, suggesting a causal relationship b etw een telomere sh o rt
ening and cellular aging.
Designs for telom ere inhibitors to fight cancer and inducers to reverse aging are already in the works, and the implications could be profound should they p a n out. Still, the theory is no t w ith o u t its critics. One is Hayflick himself, n o w a faculty m em b er at the U niver
sity of California at San Francisco Medical School and past president of the Gerontological Society of America. He believes telomeres m ay be useful for u n d e rsta n d in g the u ltim ate limits of life span b u t do n o t reveal m u c h about how to directly influence the aging process.
A nother is n o ted molecular biologist Harry Rubin. Rubin has attacked the widely held assu m p tio n th a t there is an intrinsic fixed lim it to the n u m b e r of divisions vertebrate cells can undergo. He argues th a t studies supporting this idea have been carried ou t in vitro or ex-vivo (removed and p u t back in the body), and it is being placed in these u n n a tu ra l environm ents th a t stops cells from divid
ing. He takes his critique further, suggesting th a t results of such studies actually support a m ore stress-based m odel of aging, in th a t it is external factors (putting cells in a foreign culture) th a t causes a reduction in grow th rate, as opposed to any inherited genetic tim e table. In other words, it is the cells' inability or failure to successfully ad ap t to a stressful environm ent th a t is m ost responsible for their failure to replicate, perhaps paralleling conditions created over a life
tim e of external assaults to the hom eostasis of th e body from free radicals and other factors th a t m ay produce such dam aging effects.
The tru th about h o w and w h y we age surely involves elem ents from b o th the dam age and program m ed camps. M any of us w ould like to believe w e can exercise absolute control over the speed at w hich we w ear dow n by im plem enting proper dietary and lifestyle habits. However, there is simply no denying the fact th a t the oldest recorded m a n to date lived to be a m ere 120, a n d m ost never m ake it anyw here close.
W h en m easured collectively, h u m a n beings, like fruit flies, fall w ith in a generally recognized life span th a t is, to some degree, ge
netically determ ined. The average life expectancy in the United States is approxim ately seventy-six years. Additionally, the large- scale New E ngland C entenarian Study, in association w ith Harvard
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M edical School, shows th a t there are approxim ately forty th o u sa n d people over th e age of one h u n d r e d in the U.S. This translates to 1 c en ten arian per 10,000 Americans, based on a population of m ore th a n 250,000,000. Ninety per cent of these lucky few are w om en.
Similar p attern s have been found in o th er industrialized countries.
We are, however, individuals.
W hy can some people r u n a m a ra th o n at age seventy-five w hile others drop dead from a stroke at forty? Science increasingly su g gests th a t th e difference m ay well involve th e daily, personal choices w e m ak e concerning h o w w e treat our bodies. Before exploring such choices, it is im p o rta n t to step beyond th e cellular level a n d look m ore practically at w h a t h a p p e n s to us as w e age in order to u n d e r sta n d h o w to prevent it.