Nota bene: aging. Sensing old age.

Abstract

W e humans sense old age through feeling those creaky joints or observing those graying hairs but, according to Apfeld and Kenyon reporting in a recent issue of Nature ([1][1]), the nematode worm senses its age by smelling and tasting the environment. These investigators show that worms with defective olfactory organs (that would normally detect odor molecules in the environment) live longer than their comrades with a keener sense of smell. By comparing these worms with other mutant nematodes that live an unusually long time, the researchers found clues to how a reduced ability to “smell the roses” might lengthen life-span. The worm's olfactory sense organs—amphids on the head and phasmids on the tail—are composed of a cluster of nerve cells, the ends of which are modified into cilia. The cilia are encircled by a sheath and a socket cell that form a pore in the worm's skin through which the tips of the cilia protrude (see photograph). Odor molecules and soluble compounds bind to G protein-coupled receptors (similar to the olfactory and taste receptors of mammals) located at the tip of each cilium. Worms with a poor sense of smell—because their olfactory organs have defective or absent cilia, blocked pores, or damaged sheaths—live much longer, yet are otherwise normal (for example, their feeding and reproductive behaviors are unchanged). Mutations in TAX-4—a channel regulated by cyclic GMP that sits under the G protein-coupled receptor and transduces the sensory signals into electrical impulses—also imbue the worm with a longer life. But mutations in the worm's olfactory machinery are not the only defects that extend its life-span. In an earlier study, Kenyon's group found that defects in the reproductive system could prolong life by decreasing the activity of DAF-2 (a receptor for an insulin-like molecule) and increasing the activity of DAF-16 (a transcription factor). By looking at worms defective in both sensory perception and reproduction, Apfeld and Kenyon worked out a putative pathway through which smell might influence a worm's longevity. ![Figure][2] CREDIT: CORI BARGMANN An environmental signal, perhaps produced by bacteria (the worm's favorite food), binds to G protein-coupled olfactory receptors on sensory cilia activating TAX-4, which then incites electrical activity in the sensory neurons. This activity triggers secretory vesicles in the neurons to release insulin-like molecules, which bind to DAF-2 and activate the insulin-like signaling pathway. This then switches on genes that will ensure the worm dies at the usual age (2 weeks). A reduced ability to sense olfactory cues would result in a decrease in DAF-2 activation and an increase in life-span. This chain of events is not proven, but insulin-like molecules that might bind to DAF-2 have been identified in the nematode. Such a pathway would also make physiological sense. After all, if food is scarce it may behoove the worm to live longer to ensure that it has the chance to produce its full quota of offspring. A scarcity of food also promotes longevity in rodents and primates (and perhaps people). But so far it seems that in these more complicated creatures a poor sense of smell is not a harbinger of a ripe old age. 1. [↵][3]1. J. Apfeld, 2. C. Kenyon , Nature 402, 804 (1999). [OpenUrl][4][CrossRef][5][PubMed][6][Web of Science][7] 2. 1. H. Hsin, 2. C. Kenyon , Nature 399, 362 (1999). 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