Kishi Shuji, Slack Barbara E, Uchiyama Junzo, Zhdanova Irina V
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA.
Gerontology. 2009;55(4):430-41. doi: 10.1159/000228892. Epub 2009 Jul 27.
Understanding the molecular mechanisms of aging in vertebrates is a major challenge of modern biology and biomedical science. This is due, in part, to the complexity of the aging process and its multifactorial nature, the paucity of animal models that lend themselves to unbiased high-throughput screening for aging phenotypes, and the difficulty of predicting such phenotypes at an early age. We suggest that the zebrafish genetic model offers a unique opportunity to fill in this gap and contributes to advances in biological and behavioral gerontology. Our recent studies demonstrated that this diurnal vertebrate with gradual senescence is an excellent model in which to study age-dependent changes in musculoskeletal and eye morphology, endocrine factors, gene expression, circadian clock, sleep and cognitive functions. Importantly, we have also found that the presence of a senescence-associated biomarker ('senescence-associated beta-galactosidase') can be documented during early zebrafish development and is predictive of premature aging phenotypes later in adult life. The availability of mutant 'genotypes' with identified aging 'phenotypes' in zebrafish, in combination with a wealth of information about zebrafish development and genetics, and the existence of multiple mutant and transgenic lines, should significantly facilitate the use of this outstanding vertebrate model in deciphering the mechanisms of aging, and in developing preventive and therapeutic strategies to prolong the productive life span ('health span') in humans.
了解脊椎动物衰老的分子机制是现代生物学和生物医学科学面临的一项重大挑战。部分原因在于衰老过程的复杂性及其多因素性质、适合对衰老表型进行无偏倚高通量筛选的动物模型匮乏，以及在幼年时预测此类表型的困难。我们认为斑马鱼遗传模型提供了一个填补这一空白的独特机会，并有助于生物和行为老年学的进展。我们最近的研究表明，这种具有渐进性衰老的昼行性脊椎动物是研究肌肉骨骼和眼睛形态、内分泌因素、基因表达、生物钟、睡眠和认知功能随年龄变化的极佳模型。重要的是，我们还发现，在斑马鱼早期发育过程中可以记录到衰老相关生物标志物（“衰老相关β-半乳糖苷酶”）的存在，并且它可以预测成年后期的早衰表型。斑马鱼中具有已确定衰老“表型”的突变“基因型”，加上大量有关斑马鱼发育和遗传学的信息，以及多个突变和转基因品系的存在，应该会显著促进这个出色的脊椎动物模型在解读衰老机制以及制定预防和治疗策略以延长人类有效寿命（“健康寿命”）方面的应用。
