Motecutar Microbiology (1990) 4(3). 337-343
MicroReview Aging and senescence of the budding yeast Saccharomyces cerevisiae S. M. Jazwinski Department of Biochemistry and Molecular Biology. Louisiana State University Medicat Center, New Orteans, Louisiana 70112, USA. Summary The budding yeast Saccharomyces cerevisiae has a limited Irfe span, defined by the number of times an individual cell divides. Longevity in this organism involves a genetic component. Severat morphological and physiological changes are associated with yeast aging and senescence. One of these, an increase in generation time with age, provides a 'biomarker' for the aging process. This increase in generation time has revealed the operation of a 'senescence factor(s)', which is likely to be a product of age-specific gene expression. The Cell Spiral Modet indicates coordination of successive cell cycles to be inherent in the determination of tife span. It is proposed that tife expectancy depends on the function of a stochastic trigger during aging that sets in motion a programme leading to cell senescence and death.
The phenomenology of yeast aging The possibitity that changes occur in the reproductive properties of yeast cells as a function of age was first raised by Barton (1950). Mortimer and Johnston (1959) demonstrated that the yeast life span, understood as the budding or reproductive (replicative) capacity of the cell, is limited. An individuat yeast cett divides a certain number of times, after which it assumes a granutar appearance and frequently lyses. These manifestations are equated with cett death. The question of any post-mitotic tife span remains open; however, this possibility is not attractive because it is difficult to associate any terminal differentiation process in yeast with the sort of cessation of cetl division observed, tt is ctear that the metric of the yeast life span is the number of times the celt divides and not its chronotogicat age (Mutler et ai. 1980). The probabilistic nature of aging and senescence in yeast is evidenced by Received 14 August, 1989; revised 27 October, 1989. Tel. (504)568 4725,
the fact that atthough the mean life span of a strain usually falts in the range of 20 to 30 generations, an individuat cett may divide as few as two and as many as some fifty times. Furthermore, the 'daughter' cett has an equat probabitity of enjoying a fult tife span (Johnston, 1966), A typlcat tife span determination is presented in Fig. 1A. A ptot of the mortality rate as a function of age (Fig. 1B) reveals that this rate increases exponentiatty (Pohley, 1987; Jazwinski ef ai, 1989), a haltmart< of 'normat' aging in other species including humans. Each time a cetl divides, it is marked in the process by a chitin-containing bud scar (Barthotomew and Mittwer, 1953; Cabib etai, 1974). These bud scars accumutate on the 'mother' cetl, and naturatly were suspected to be the source of the cett's timited life span. Few ceils exhaust even one-half of the 100 or so sites on the yeast celt wait that coutd accommodate bud scars. The cett surface expands to accommodate these bud scars (Beran ef ai, 1967), a fact rarety taken into consideration, and indeed the areat increase with each cetl cycte surpasses what is necessary to achieve this (Johnson and Lu, 1975). Atthough it has been stated that bud scars do not overlap each other, this is not entirety convincing. For ail of these reasons, it is not reatty ctear how many bud scars a celt can potentiatly accrue. A wide variabitity exists in the tongevity of individual ceils of any given strain. Additionatty, mean tife span varies considerabty from one strain to another. These facts render exhaustion of budding sites unlikely as an exptanation for the aging of the yeast cetl. A more sophisticated view of the timitation placed on tife span by the accumutation of bud scars states that they limit metabolicalty active surface to votume (tvlortimer and Johnston, 1959), However, this atso does not hotd up to experimentai scrutiny (Multer, 1971). Finalty, the accumutation of chitin in the cett wati does not appear to be the sote or even the major determinant of yeast tife span (Egitmez and Jazwinski, 1989). The occurrence of ageassociated cetl wait and membrane changes that tead to senescence is a possibility that has not been ruted out. Ethanot, a membrane-active compound, has been reported to increase life span (Mutler ef ai, 1980). This resutt is difficutt to interpret, however, because of the enhanced rote of mitochondrial respiration when 2% ethanot reptaces the 2% glucose in the growth medium.
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MicroReview Aging and senescence of the budding yeast Saccharomyces cerevisiae S. M. Jazwinski Department of Biochemistry and Molecular Biology. Louisiana State University Medicat Center, New Orteans, Louisiana 70112, USA. Summary The budding yeast Saccharomyces cerevisiae has a limited Irfe span, defined by the number of times an individual cell divides. Longevity in this organism involves a genetic component. Severat morphological and physiological changes are associated with yeast aging and senescence. One of these, an increase in generation time with age, provides a 'biomarker' for the aging process. This increase in generation time has revealed the operation of a 'senescence factor(s)', which is likely to be a product of age-specific gene expression. The Cell Spiral Modet indicates coordination of successive cell cycles to be inherent in the determination of tife span. It is proposed that tife expectancy depends on the function of a stochastic trigger during aging that sets in motion a programme leading to cell senescence and death.
The phenomenology of yeast aging The possibitity that changes occur in the reproductive properties of yeast cells as a function of age was first raised by Barton (1950). Mortimer and Johnston (1959) demonstrated that the yeast life span, understood as the budding or reproductive (replicative) capacity of the cell, is limited. An individuat yeast cett divides a certain number of times, after which it assumes a granutar appearance and frequently lyses. These manifestations are equated with cett death. The question of any post-mitotic tife span remains open; however, this possibility is not attractive because it is difficult to associate any terminal differentiation process in yeast with the sort of cessation of cetl division observed, tt is ctear that the metric of the yeast life span is the number of times the celt divides and not its chronotogicat age (Mutler et ai. 1980). The probabilistic nature of aging and senescence in yeast is evidenced by Received 14 August, 1989; revised 27 October, 1989. Tel. (504)568 4725,
the fact that atthough the mean life span of a strain usually falts in the range of 20 to 30 generations, an individuat cett may divide as few as two and as many as some fifty times. Furthermore, the 'daughter' cett has an equat probabitity of enjoying a fult tife span (Johnston, 1966), A typlcat tife span determination is presented in Fig. 1A. A ptot of the mortality rate as a function of age (Fig. 1B) reveals that this rate increases exponentiatty (Pohley, 1987; Jazwinski ef ai, 1989), a haltmart< of 'normat' aging in other species including humans. Each time a cetl divides, it is marked in the process by a chitin-containing bud scar (Barthotomew and Mittwer, 1953; Cabib etai, 1974). These bud scars accumutate on the 'mother' cetl, and naturatly were suspected to be the source of the cett's timited life span. Few ceils exhaust even one-half of the 100 or so sites on the yeast celt wait that coutd accommodate bud scars. The cett surface expands to accommodate these bud scars (Beran ef ai, 1967), a fact rarety taken into consideration, and indeed the areat increase with each cetl cycte surpasses what is necessary to achieve this (Johnson and Lu, 1975). Atthough it has been stated that bud scars do not overlap each other, this is not entirety convincing. For ail of these reasons, it is not reatty ctear how many bud scars a celt can potentiatly accrue. A wide variabitity exists in the tongevity of individual ceils of any given strain. Additionatty, mean tife span varies considerabty from one strain to another. These facts render exhaustion of budding sites unlikely as an exptanation for the aging of the yeast cetl. A more sophisticated view of the timitation placed on tife span by the accumutation of bud scars states that they limit metabolicalty active surface to votume (tvlortimer and Johnston, 1959), However, this atso does not hotd up to experimentai scrutiny (Multer, 1971). Finalty, the accumutation of chitin in the cett wati does not appear to be the sote or even the major determinant of yeast tife span (Egitmez and Jazwinski, 1989). The occurrence of ageassociated cetl wait and membrane changes that tead to senescence is a possibility that has not been ruted out. Ethanot, a membrane-active compound, has been reported to increase life span (Mutler ef ai, 1980). This resutt is difficutt to interpret, however, because of the enhanced rote of mitochondrial respiration when 2% ethanot reptaces the 2% glucose in the growth medium.
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