[John C. Guerin C.V.]

Extending the Healthy Lifespan of Humans: the Essence is Negligible Senescence

The project's research is now uncovering the mechanisms that allow continued vitality in these long-lived animals. With that knowledge it will help us understand why humans are healthy for many years, but then start having more and more age-related problems. Because of our aging population, the research will have enormous benefits for humanity, not only in greater health and enjoyment of later years, but in controlling the escalating costs of Social Security and medical care.

Only a few projects in the world study long-lived animals. AgelessAnimals reports the latest research to both general and gerontological audiences. Current research from 14 pilot studies, located at twelve universities around the United States and two in Europe, encompass topics from Free-radical damage to DNA Micro-array gene expression.

Abstract:
Field observations have suggested for quite some time that certain fish, turtles and whales have extremely long maximum lifespan potential. Age validation techniques have since confirmed these observations, but scientific analysis to understand the genetic and biochemical basis of this longevity has occurred only recently. On the Home page, the term 'negligible senescence' is defined, background information about long-lived animals is discussed, and age validation techniques are listed. Subsequent website pages list the various projects to date, including research results.

Introduction to Negligible Senescence:
Aging research has advanced dramatically in the last several years, with many recent discoveries about the biochemical and genetic components of aging. But curiously, one potential area of study for aging research identified over 70 years ago has not advanced until recently - the analysis of long-lived animals. In the 1930's it was proposed that some fish do not show signs of senescence (Bidder 1932). Even though biological tools such as histology existed at that time, no known efforts were made to examine these animals.

This new area of study in biomedical gerontology has the potential to reveal the genetic and biochemical processes that long-lived animals use to retard aging. Although rockfish (genus Sebastes) have been the main focus, one of our studies is on turtles, and whales are under consideration for future studies. Leonard Hayflick, discoverer of the "Hayflick limit" of cellular senescence and an advisor to this project, states that "Guerin's project is not only unique, but probes an area of almost total neglect in biogerontology, yet an area with more promise to deliver valuable data than, perhaps, any other".

Background on Negligible Senescence:
Caleb Finch at USC coined the term "negligible senescence" to describe very slow or negligible aging (Finch 1990). He listed several animals with this characteristic, including rockfish, sturgeon, turtles, bivalves and possibly lobsters. Later in a paper from the first Symposium on Organisms with Slow Aging (which the Director of this project also spoke at), Finch further described criteria to test the occurrence of negligible aging. These include no observable age-related increase in mortality rate or decrease in reproduction rate after maturity, and no observable age-related decline in physiological capacity or disease resistance (Finch and Austad 2001).

Accurate age determination is important in studying long-lived animals. In turtles, the determination of minimum age is relatively straightforward, using tag and recapture methods. In many fish, the most common technique is the analysis of annual growth rings in the otolith, or ear bone (Bagenal 1974, McFarlane and Beamish 1995). Two recent international symposia have focused entirely on the importance of otolith measurement in fish life history studies (Secor et al. 1995, Fossum et al. 2000). Another technique used by fisheries management to provide an independent age estimate is the radiometric approach, which utilizes a known radioactive decay series in the core of bones (Bennett et al. 1982, Campana et al. 1990). Recent research that showed whales live over 200 years in good health used aspartic acid racemization (George 1999).

Zoos have also compiled longevity information. Alligators have been recorded up to eighty years of age, although it is uncertain if death was due to senescence or environmental factors (Snider, A.T., Bowler, J.K. Longevity of Reptiles and Amphibians in North American Collections 1992, and also personal communication with the Cincinnati Zoo 2001). Green sea turtles have been estimated to take up to a maximum of 50 years to reach maturity in the wild, due to their low protein diet (Bjorndal 1985). This is significant because delayed reproduction is usually associated with a very slow rate of aging. A 1994 issue of Gerontology was devoted to aging in cold-blooded vertebrates; it compiled research showing that even though some fish are long-lived, interestingly many are short-lived and have senescence similar to that seen in mammals (Patnaik, B.K. (Ed.), 1994).

Many of the above mentioned animals were originally considered for the initial study of negligible senescence. But in 1997 the project received data from the Alaska Fish and Game on randomly sampled Yelloweye rockfish, commercially caught off of Sitka, Alaska. The charts they provided showed that 16% of the fish going to people's dinner tables were 50 years of age or older, with several over 100 years old! With the knowledge that long-lived animals of this age were commercially available, rockfish became the major research effort of the AgelessAnimals project.

In a very intriguing analysis, the project's Fish Ecologist, Gregor M. Cailliet, determined that rockfish have both short-lived and long-lived members in the same genus (Cailliet 2001). He found that maximum rockfish longevity ranges in age from 12 years for the calico rockfish to 205 years for the rougheye rockfish. Future studies on the project will compare genetic and biochemical measurements between short-lived and long-lived rockfish.