Research on Aging: The End of the Beginning

[Guest guest]

Hi All, Since the below was generously forwarded to me, I would like to

share it with you in another form that takes less computer space than a PDF.

Aging and CR are featured.

Cheers, Al.

Research on Aging:

The End of the Beginning

INTRODUCTION

Comics, poets, and sages have all expounded

on what it means to age. But only now

can we begin to converse about the biology of aging.

Why and how do we age? Re-searchers

have asked these questions, and some answers

are finally emerging.

To speed up this process, in 2001 Science, with

the aid of a major gift from the Ellison

Medical Foundation, launched the Science of

Aging Knowledge Environment

(SAGE KE). This Web site provides

“one-stop shopping” for researchers in the field of

aging and related disciplines. For a start, SAGE KE

helps researchers keep up with the literature.

We offer scientist-authored commentaries and

journalist-written news stories on current research

findings. Visitors to our site can find authoritative

reviews written by prominent scientists and can

access a storehouse of community information:

case studies, discussions, a calendar of meetings

on aging, a database of genes/interventions and

mouse models related to aging, and a directory of

people working in the field. In addition, SAGE KE

houses a virtual journal whose search engine is

trained to find new papers on aging no matter

where they are published. Access to SAGE KE is

free until 26 March 2003.

In this joint special issue, Science and SAGE KE

have teamed up to showcase highlights from

what might be called the “end of the beginning”

of research on aging. We have focused on physiological

mechanisms underlying processes of

aging, rather than on the large array of debilitating

and costly disorders that so commonly

emerge during the latter half of the life-spans of

human beings. The reason for this decision is illustrated

in the figure on page 1341. The “one

disorder at a time” approach has limited power

to delay death; rather, it is through deciphering

the biological underpinnings of processes of aging

that scientists will likely discover ways to extend

the human life-span. This problem is being

attacked from several angles, and we are seeing

some emerging themes.

Feeding fewer calories to rodents—and likely

primates too—makes them more stress-resistant

and, perhaps because they are more stress-resistant,

they live considerably longer. Several other animal

model systems have mutation-induced metabolic

states that are similar to those produced by

calorie restriction and are also designed

for withstanding adverse conditions—the

dauer phase in the worm Caenorhabditis

elegans, for example. These mechanisms

are probably related to ancient and adaptive

types of diapauses: time-outs from the

business of reproduction while awaiting

more favorable conditions. In their Review,

Longo and Finch (p. 1342) compare

these long-lived creatures, ranging

from yeast to mice, and point out the

commonalties, such as defects in

the insulin/insulin-like growth factor 1

signaling pathway. In SAGE KE, Masoro

surveys the history of research

on calorie restriction, and Hopkin

explores the down-side of eating less.

It turns out to be more than just hunger pangs.

Genetic approaches in model

systems have been a gold mine in

divulging which processes can tune

life-span up or down. And, when

interpreted in the context of more

traditional endocrinological approaches,

genetic results point to endocrine regulation

of critical life-span–controlling functions

as a possible common pathway, as

summarized in Tatar et al.’s Review (p.

PAGE 1346). In SAGE KE, Davenport explores

new research that probes how well phenomena

observed in the lab relate to those

that occur in natural environments.

[Figure]

Research on Aging: Biggest Bang for the Buck?

The End of the Beginning Just Like Today —average 50-year-old woman lives to 81

Cure Cancer Today[…………83]

Cure Heart Disease Today[……..84]

Cure Cancer and Heart Disease Today[……..87]

Cure Cancer, Heart Disease, Stroke, and Diabetes Today[…..86]

Slow Down Aging[………………………………..110]

What are the critical downstream functions

that are important for aging? Several

answers are on the table, and they may

well all be right. Some lines of

evidence point to silencing of

the expression of certain genes

as a key regulator, argue Hekimi

and Guarente in their Review (p.

1351), although the cumulative damage

inflicted by reactive oxygen species is

also a likely culprit. Indeed, in their Review,

Hasty and co-workers (p. 1355)

summarize how damage to DNA, perhaps

by such oxygen radicals, can be better

understood as a cause of aging through

the comparison of clinical syndromes

and mouse models. In SAGE KE,

Shcherbakova and colleagues zero in on

the DNA polymerases, which repair DNA

damage, at least when they are working

optimally; and Walter et al. examine the

special case of germline genome stability.

But the topic of aging is far broader

than genes and hormones and ultimately

affects all of our daily lives in one way or

another. For researchers in the field, their

pursuits in the lab can also have a personal

component, as seen firsthand in Guarente’s

book Ageless Quest, reviewed by

Promislow in this issue (p. 1319). And for

many, aging can be painful, as is

poignantly clear in Bush’s review of

DeBaggio’s recent book recounting his

own experiences with Alzheimer’s disease

(p. 1318). But there is some good news.

Two News stories by Helmuth, one in

Science (p. 1300) and one on SAGE KE,

give us some reasons for looking forward

to the latter half of our lives. Scores on

vocabulary tests appear to improve with

age, and older people often outperform

younger ones in interpersonal tasks.

Research on aging is increasingly important

in the public policy arena as well.

The Policy Forum by Juengst (p. 1323) argues

that we need to start thinking about

the practical and ethical ramifications of

research on aging now, before the decisions

are made for us by circumstance. We

at Science also believe that public debate

on issues surrounding aging is essential.

Consequently we will be launching, in

March 2003, a new portal of SAGE KE to

catalyze public discourse about issues surrounding

aging. Built in partnership with

the Alliance for Aging Research, this new

site—called SAGE Crossroads—will feature

a series of Webcast debates and interviews

in which prominent figures discuss

controversies in research and policies on

aging. The first Webcast—a discussion

between Francis Fukuyama and

entitled “The Future of Aging: Pit-falls

and Possibilities”—

occurred on 12 February and focused on

the ethics of pro-longing life. This

debate, plus related news stories,

discussions, and other re-sources,

can be seen at SAGECrossroads.

net. Scientific research on biological

mechanisms of aging may be at the end

of the beginning, but the larger discussions

of why we study aging and the

proper use for this knowledge are yet in

their infancy.

Actor Charlie Chaplin once remarked

that “we are all amateurs; we don’t live

long enough to become anything else.” If

aging processes could be attenuated, humans

would have additional healthy years

to bring their personal goals to fruition.

The challenge to society will be to ensure

that those goals are compatible with the

needs of humanity.

–GEORGE M.MARTIN,KELLY LAMARCO,

EVELYN STRAUSS,AND KATRINA L.KELNER

http://SAGECrossroads.net