Sci. Aging Knowl. Environ., 30 January 2002
Vol. 2002, Issue 4, p. nw13
[DOI: 10.1126/sageke.2002.4.nw13]


Synchronized Aging: Gene regions might coordinate aging in ordinary mice (Genetics)

Katharine Miller;2002/4/nw13

Key Words: longevity genes • life-span • cancer • neoplastic

Abstract: Like the voices of a well-conducted chorus, wrinkles, gray hair, bone loss, and memory problems tend to crescendo in unison. Perhaps a single process controls the synchronous onset of these and other age-related motifs (see Miller Perspective). Support for such coordination comes from evidence that calorie restriction not only extends the life of laboratory rodents but also retards multiple diseases and other features of aging. Similarly, several mutations generate dwarf mice that age slowly before capitulating to the usual spectrum of deadly afflictions. But researchers have not known whether nonmutant populations carry genetic variations that can slow aging. Now some potential maestros of the aging process in nonmutant laboratory mice are appearing on stage. Certain chromosomal regions prolong the life of these animals by the same amount regardless of what disease ultimately fells them in old age. The results suggest that several genetic spans might direct the pace of aging even in a natural population.

Jackson and colleagues raised 278 sibling mice born to the offspring of four genetically different lab-mouse grandparents. The researchers determined when and why each animal died, and they searched the animals' genes for versions of chromosome segments, or loci, that correlate with unusually long life. They zeroed in on four such loci or pairs of loci and then assessed whether the loci they'd identified protect the animals only from cancer or slow the aging process in general, bestowing a youthful physiology that renders the mice less prone to an array of life-threatening diseases.

A large proportion of the mice--85%--had died of cancer; the other 15% had succumbed to various illnesses including infections, heart or circulatory problems, and starvation due to tooth loss. Miller and colleagues found that all four loci or pairs of loci prolong life-span to approximately the same degree in mice that die of tumors as they do in mice that die of other causes, although the findings were statistically significant for only one locus and one locus pair. Perhaps the genes (or sets of genes) at those loci postpone multiple late-life diseases by controlling the rate of aging.

To test whether their findings hold up, the researchers have embarked on a similar study of 600 animals. They also hope to determine whether the longevity loci slow aging in naturally occurring mouse strains with more genetic diversity than the inbred lab strains used for this study. In addition, they will explore whether the loci retard the appearance or progress of nonfatal age-related conditions such as cataracts, decreased immune function, and muscle atrophy. For now, the results hint that genetic loci might conduct the chorale of mammalian aging in prestissimo, adagio, or several tempos in between. By identifying these genetic directors, researchers might gain the ability to alter the rate of aging, slowing the speed at which youthful crooners turn into gray-haired croakers.

--Katharine Miller; suggested by Donna Holmes

A. U. Jackson, A. T. Galecki, D. T. Burke, R. A. Miller, Mouse loci associated with life span exhibit sex-specific and epistatic effects. J. Gerontol. A Biol. Sci. Med. Sci. 57, B9-B15 (2002). [Abstract] [Full Text]

R. A. Miller, C. Chrisp, A. U. Jackson, A. T. Galecki, D. T. Burke, Coordinated genetic control of neoplastic and nonneoplastic diseases in mice. J. Gerontol. A Biol. Sci. Med. Sci. 57, B3-B8 (2002). [Abstract] [Full Text]

Citation: K. Miller, Synchronized Aging: Gene regions might coordinate aging in ordinary mice (Genetics) Science's SAGE KE (30 January 2002),;2002/4/nw13

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