Morphological Changes Accompanying Aging In S Ratti

Autofluorescence In C. elegans, there is an increase in intestinal autofluorescence with age (Garigan et al., 2002), similar to accumulation of age-pigment (lipofuscin) seen during mammalian aging. There is a similar increase in autofluorescence with age in free-living S. ratti morphs (Gardner et al., 2004). By contrast, little such autofluorescence was seen in parasitic females, even in 11-month-old individuals (Gardner, Gems and Viney, submitted). Lipofuscin accumulation reflects organismal failure to detoxify and excrete molecular waste products. The paucity of autofluorescence in S. ratti parasitic females suggests reduced generation, and/or increased excretion, of damaged molecular constituents. This is consistent with aging occurring in the two S. ratti female morphs, but at very different rates.

Microscopic examination of aging nematodes The integrity of major anatomical features was compared in young and old S. ratti adults using differential interference contrast (DIC) and transmission electron microscopy (TEM) (Gardner et al., 2004; Gardner, Gems and Viney, submitted). Overall, the appearance of aging S. ratti free-living females was similar to that of aging C. elegans (Herndon et al., 2002). The pharynxes of older free-living S. ratti were frequently distended and blocked with bacteria. Such pharyngeal blockage has also been observed in older C. elegans (Garigan et al., 2002). The most striking morphological age changes in free-living S. ratti occurred in the intestine (Gardner et al., 2004). Whilst in one-day-old animals there were large, healthy looking refractile intestinal cells (Figure 20.4A), in the majority of four-day-old animals these cells were severely atrophied and the cytoplasm had a ragged appearance (Figure 20.4B).

By contrast, older parasitic females showed no marked degenerate changes.

TEM observations of free-living females showed numerous inclusions in the intestinal cytoplasm whose

Figure 20.4. (A-B) S. ratti free-living females viewed using differential interference contrast (Nomarski) microscopy. (A): one-day-old female; (B), four-day-old adults. (A) and (B): posterior intestine. In (A), note the large, healthy refractile intestinal cells (i). In (B), the intestine is strikingly atrophied. Anus (a). Bars = 20 ^m. (C) TEM of four-day-old free-living females with electron-dense inclusions of intestinal cells indicated by * (Bar = 2 ^m); c, cuticle; mv, microvilli; b, clump of bacteria in lumen.

Figure 20.4. (A-B) S. ratti free-living females viewed using differential interference contrast (Nomarski) microscopy. (A): one-day-old female; (B), four-day-old adults. (A) and (B): posterior intestine. In (A), note the large, healthy refractile intestinal cells (i). In (B), the intestine is strikingly atrophied. Anus (a). Bars = 20 ^m. (C) TEM of four-day-old free-living females with electron-dense inclusions of intestinal cells indicated by * (Bar = 2 ^m); c, cuticle; mv, microvilli; b, clump of bacteria in lumen.

number increased with age (Figure 20.4C). Most of these resembled lipid droplets (or possibly secondary lysosomes) within which have accumulated electron-opaque particles with a sooty appearance. By contrast, there were very few such inclusions in the intestines of parasitic females and their number did not change with age. These observations suggest that degeneration of the intestine, possibly associated with accumulation of fluorescent/electron opaque waste material, represents a pathology of aging that contributes to nematode pathology. This idea was previously put forward based on TEM studies of aging in Caenorhabditis briggsae (Epstein et al., 1972). The fact that this pathology was not detected in the intestine of the parasitic S. ratti adult is consistent with the idea that the absence of this pathology contributes to parasitic longevity.

The parasitic and free-living females morphs of S. ratti are genetically identical. Therefore differences between these morphs must be due to differences in gene expression. This being so, these differences in intestinal pathology might reflect differences in regulated biochemical processes which determine longevity and aging. One intriguing and attractive possibility is that in parasitic females there is an increase in biochemical processes promoting detoxification. Recent microarray studies of long-lived insulin/IGF-1 signalling mutants of C. elegans have implicated a broad range of detoxification processes in longevity assurance (Murphy et al., 2003; McElwee et al., 2004; Gems and McElwee, 2005). These include phase 1 and phase 2 drug detoxification, as well as anti-oxidant enzyme and chaperonin activities. Most of these processes require energy input, and excretion of solubi-lized toxic metabolites by the drug detoxification system occurs via the smooth endoplasmic reticulum. Interestingly, intestinal cells of parasitic S. ratti adults are rich with mitochondria and smooth endoplasmic reticulum.

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