Our current understanding of the biology of aging is largely the result of studies in short-lived laboratory models such as yeast, worms, flies and mice. One class of animals that may reveal some novel strategies against the destructive process of aging are those that continue to grow and reproduce throughout their life spans and age either slowly or not at all. Although several animals with negligible aging have been described many of them present practical, technical and ethical challenges for laboratory studies. As an exception, sea urchins present a unique and tractable model for the study of aging and negligible senescence. Sea urchins are a well established laboratory model that are more closely related to humans than other invertebrate models (i.e. worms and flies) and there are a large number of cellular and molecular tools available for their study. Different species of sea urchins have very different natural life spans and there are some species which display extreme longevity and negligible senescence. The long-term goals of this project are to define the molecular, cellular and physiological basis for differences in longevity between species of sea urchins and to understand the mechanisms underlying the absence of aging in the long-lived species. Preliminary genomics data have helped form our central hypothesis in which longer lived species have a greater capacity for tissue regeneration and repair and the longest lived species has a unique ability to mitigate cellular oxidative damage. The objectives of this proposal are to test this hypothesis by examining indicators of cellular damage and regeneration in the tissues of sea urchins species with different life spans;Strongylocentrotus franciscanus (life span >100 years), Strongylocentrotus purpuratus (life span 50 years) and Lytechinus variegatus (life span 4 years). Indicators of regeneration will be assessed by investigating cell proliferation and apoptosis in tissues from animals of different ages spanning the life span of each species. The capacity for repair or mitigation of damage will be assessed by measuring overall levels of cellular damage such as lipofuscin, 8-hydroxydeoxyguanosine, protein carbonyls and malondialdehyde in tissues from animals of different ages spanning the life span of each species. Comparisons between these long-, intermediate- and short-lived species will facilitate the identification of critical cellular and molecular pathways that determine their different life histories and will uncover mechanisms of negligible senescence in the long-lived species. The use of sea urchins as models for aging provides a novel approach to uncover mechanisms leading to slower rates of aging and mechanisms for unusual resistance to senescent phenotypes. Since sea urchins are more closely related to humans than are other invertebrate models that have provided significant insight into the process of aging, there is little doubt that the information gained from these studies will be directly relevant to human biology and may ultimately lead to new avenues for prevention or treatment of age-related diseases.

Public Health Relevance

Sea urchins present a unique model for studying aging due to the existence of species with very different natural life spans including some species which display extreme longevity and negligible aging. The study of sea urchins may reveal some novel strategies resulting in slower rates of aging and mechanisms for resistance to senescent phenotypes which may ultimately lead to new avenues for the prevention or treatment of age- related diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG039761-02
Application #
8337830
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Murthy, Mahadev
Project Start
2011-09-30
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$164,855
Indirect Cost
$43,220
Name
Bermuda Institute of Ocean Sciences, Inc
Department
Type
DUNS #
875635161
City
New Hyde Park
State
NY
Country
United States
Zip Code
11040
Du, Colin; Anderson, Arielle; Lortie, Mae et al. (2013) Oxidative damage and cellular defense mechanisms in sea urchin models of aging. Free Radic Biol Med 63:254-63