Growth Rate And Overall Size As Aging Markers

Most organisms exhibit determinate growth—up to the point at which growth no longer occurs. However, indeterminate growth may occur when it offers advantages in fitness or reproductive prowess. It was already hypothesized that zebrafish exhibit a capacity for unlimited growth (Gerhard et al., 2002), and our study supported this notion. This is clearly different from humans and other mammals that cease growing after reaching sexual maturation (Figure 28.4).

This indefinite growth regulation may indicate an evolutional attempt to compensate for senescence with age. Similarly, age did not seem to simply deter continued growth, as small aged fish retained comparable ability to grow as small young fish. Instead, growth merely slowed as body size increased regardless of age.

On a different note, other factors such as environmental conditions can play a pivotal role in modulating growth regulation. Indeed, we have demonstrated that given adequate nourishment, living space available or density conditions directly governed the mean final size reached by fish in each tank. It may be postulated that density could act as a trigger to stop growth and to affect other processes by stimulating some sort of "space" sensors in zebrafish that allow them monitor their own surroundings, analogous to normal cells that stop division in response to contact inhibition. Alternatively, high density conditions may stimulate some form of communication with other members within close proximity, simulating the function of pheromones in insects. While this remains to be elucidated in future studies, it was important for us to establish

Figure 28.4. Potential differences in growth and aging between zebrafish and humans. Zebrafish continue growth past sexual maturation throughout life, with remarkable regenerative capability given adequate food, space, and good husbandry. On the other hand, human and other mammals cease growing after reaching sexual maturation as their function of age. The illustration provided here is modified from the original Japanese literature, having the translated title ''Learning Biology through Medaka Fish,'' which was written by Nobuo Egami in 1989.

egg Baby Adult Aged Man

Figure 28.4. Potential differences in growth and aging between zebrafish and humans. Zebrafish continue growth past sexual maturation throughout life, with remarkable regenerative capability given adequate food, space, and good husbandry. On the other hand, human and other mammals cease growing after reaching sexual maturation as their function of age. The illustration provided here is modified from the original Japanese literature, having the translated title ''Learning Biology through Medaka Fish,'' which was written by Nobuo Egami in 1989.

density-dependence of growth before undertaking further experiments on zebrafish growth and aging.

Our current data suggest that the propensity to grow can decrease with increased size, but not simply chronological age. Both older (18-30 months) and younger (6-18 months) fish exhibited similar patterns of growth throughout their lives as long as their sizes are almost same, indicating that they are similar in ''biological age'' albeit different in chronological ages. Subsequently, growth never clearly plateaued or stopped altogether up to the end of the final measurement, supporting the indefinite growth in zebrafish.

IGF-1 is known to play crucial roles in growth and development in all vertebrates. Several lines of evidence from studies in a variety of vertebrate species suggest that the ligands (IGFs), receptors (IGF receptors), and ligand-binding proteins (IGF-binding proteins) evolved early during vertebrate evolution (Barbieri et al., 2003; Katic and Kahn, 2005). While central action sites of IGF-1 in invertebrates and higher vertebrates are currently well understood, little is known in the teleost models where their tissues and organs sometimes undergo continual and indeterminate growth, except for some fish of commercial importance. However, the IGF-1 signal that involves downstream signaling molecules, such as members in the protein deacetylase Sir2 family or the forkhead transcription factors FoxO subgroup, is believed to be one of the most prominent aging-associated pathways. Actually, CR definitely links up with the IGF-1 signaling pathway. In this respect, there is an exception to the common notion that CR extends lifespan in some fish, because ''ferox trout'' achieve long life by eating more, not less (Mangel and Abrahams, 2001). Most recently, the lifespan of guppies with CR (low food) was not extended, compared with the high-food population, and total fecundity are higher in high-food population with reproduction throughout their lives and with subsequent reproductive senescence (Reznick et al., 2004). Thus apparent patterns of senescence in guppies derived from natural populations, with respect to either mortality or reproduction, were not simply controlled by levels of food availability in the laboratory, according to the common notion. Therefore, fish may have alternative or different control mechanisms of the IGF-1/Sir2/FoxO pathways in their fitness. Further investigations of this pathway in the zebrafish model may reveal a novel control mechanism between CR and aging in lower vertebrates.

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Blood Pressure Health

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