The gerontogenes
 age‐1
 and
 daf‐2
 determine metabolic rate potential in aging
 Caenorhabditis elegans

Vanfleteren, Jacques R.; Vreese, Annemie De

doi:10.1096/fasebj.9.13.7557026

Cited by 141 publications

(83 citation statements)

References 6 publications

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“…Extension of lifespan by DR was found to occur in chico 1 flies (Clancy et al, 2002). This finding is consistent with similar studies performed in C. elegans (Vanfleteren & De Vreese, 1995;Lakowski & Hekimi, 1998) and, potentially, mice (Bartke, 2001). Yet when chico 1 mutant lifespan was examined over a range of nutritional conditions, it was found to peak at a higher level of nutrition than that of wildtype flies (Clancy et al, 2002) (Fig.…”

Section: Six Ways To Avoid Being Misled By Lifespan Interaction Studiessupporting

confidence: 90%

“…Given that daf-2(e1370) is a class 2 allele, interaction studies with clk-1 , eat-2 , dietary restriction, maleness or germline ablation may potentially be confused by the presence of some of the many pleiotropic defects. For example, the reduction of feeding by daf-2(e1370) adults at higher temperatures may confound studies of interactions between daf-2 and dietary restriction (Vanfleteren & De Vreese, 1995;Lakowski & Hekimi, 1998), or metabolic rate (Van Voorhies & Ward, 1999;Vanfleteren & De Vreese, 1995). Moreover, studies of interactions between daf-12 (which mediates TGF-β signalling) and different alleles of daf-2 have demonstrated that the results of interaction studies may depend upon whether a class 1 or a class 2 daf-2 allele is present (Larsen et al ., 1995;Gems et al, 1998).…”

Section: Effects On Survival Through More Than One Mechanismmentioning

confidence: 99%

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Interpreting interactions between treatments that slow aging

2002

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SummaryA major challenge in current research into aging using model organisms is to establish whether different treatments resulting in slowed aging involve common or distinct mechanisms. Such treatments include gene mutation, dietary restriction (DR), and manipulation of reproduction, gonadal signals and temperature. The principal method used to determine whether these treatments act through common mechanisms is to compare the magnitude of the effect on aging of each treatment separately with that when two are applied simultaneously. In this discussion we identify five types of methodological shortcomings that have marred such studies. These are (1) submaximal lifespan-extension by individual treatments, e.g. as a result of the use of hypomorphic rather than null alleles; (2) effects of a single treatment on survival through more than one mechanism, e.g. pleiotropic effects of lifespan mutants; (3) the difficulty of interpreting the magnitude of increases in lifespan in double treatments, and failure to measure and model age-specific mortality rates; (4) the non-specific effects of life extension suppressors; and (5) the possible occurrence of artefactual mutant interactions. When considered in the light of these problems, the conclusions of a number of recent lifespan interaction studies appear questionable. We suggest six rules for avoiding the pitfalls that can beset interaction studies.

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Section: Six Ways To Avoid Being Misled By Lifespan Interaction Studiessupporting

confidence: 90%

Section: Effects On Survival Through More Than One Mechanismmentioning

confidence: 99%

Interpreting interactions between treatments that slow aging

2002

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“…The dauer stage represents the natural ability of C. elegans to survive for an extended period during adverse conditions. Mutations in certain genes that regulate dauer formation are known to result in changes of the adult life span (Finch and Ruvkun, 2001;Jia et al, 2004;Vanfleteren and De Vreese, 1995), including genes for insulin/IGF-1 signaling (Gems et al, 1998;Kenyon et al, 1993). We aimed to identify changes in transcript abundance common to both types of extended longevity, which may represent a shared mechanism for modulating life span.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, the RNAi screens show that a knockdown in expression of the nucleus-encoded subunits of cytochrome c oxidase (F26E4.6, F26E4.9 Y37D8A.1 and W09C5.8) extends longevity, albeit with reduced growth and fecundity. Although a link between mutants with lowered metabolic rate and longevity has been established in C. elegans (Vanfleteren and De Vreese, 1995), it remains a possibility that the nematode may extend longevity not only by reducing oxidative phosphorylation, but by making it more efficient and reducing its production of ROS. A higher ratio of complex IV to complex III activity might accomplish this.…”

Section: Discussionmentioning

confidence: 99%

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

Ruzanov

Riddle

Marra

et al. 2007

Experimental Gerontology

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SummaryWe used Serial Analysis of Gene Expression (SAGE) to compare the global transcription profiles of long-lived mutant daf-2 adults and dauer larvae, aiming to identify aging-related genes based on similarity of expression patterns. Genes that are expressed similarly in both long-lived types potentially define a common life-extending program. Comparison of eight SAGE libraries yielded a set of 120 genes, the expression of which was significantly different in long-lived worms versus normal adults. The gene annotations indicate a strong link between oxidative stress and life span, further supporting the hypothesis that metabolic activity is a major determinant in longevity. The SAGE data show changes in mRNA levels for electron transport chain components, elevated expression of glyoxylate shunt enzymes and significantly reduced expression for components of the TCA cycle in longer-lived nematodes. We propose a model for enhanced longevity through a cytochrome c oxidase-mediated reduction in reactive oxygen species commonly held to be a major contributor to aging.

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“…The daf-16 gene encodes for a forkhead transcription factor, which regulates the activity of numerous genes. The specific genes are currently unknown, but daf-2 mutants have increased levels of catalase, superoxide dismutase, isocitrate dehydrogenase, isocitrate lyase, malate synthase and lower levels of acid phosphatase and alkaline phosphatase (98), demonstrating that a large number of enzymatic proteins are likely affected.…”

Section: Insulin Resistance and Longevity: Beyond Glucosementioning

confidence: 99%

Endocrine and metabolic changes in human aging

Banks

Morley

2000

AGE

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"Aging and death are inevitable. We have no desire to prolong life, if such prolongation entails only added days and years of misery and suffering. On the other hand, for the first time in history, man has within his grasp potent medications of many kinds, among the more important of which are specific hormones capable of retarding if not stopping some of the undesirable features of growing old". Thomas Hodge McGavack Geriatrics 18:181-191 (1963) ABSTRACT Numerous alterations in hormonal secretion occur with aging. In general, these tend towards a disintegration of the normal cyclic secretory patterns resulting in lower total circulating levels. In addition, declines in receptors and postreceptor function further decreases the ability of the hormonal orchestra to maintain coordinated function throughout the organism. Clues to some of these agerelated changes in humans may come from the study of simpler organisms where regulatory systems are known to modulate the aging process. In particular, the interactions among the environment, hormones, and insulin receptor genes have led to new insights into the genetic control of longevity and the development of syndrome X.It is now well established, as summarized in Table 1, that the levels of many hormones are altered with aging (1). Some hormonal levels decrease, reflecting endocrine gland failure, whereas others increase, often because of end organ failure due to a decrease in receptors or a failure of postreceptor function. In the last decade, it has become popular to look to hormone replacement therapy as a mechanism to reverse the aging process. It has become popular to consider this the "hormonal fountain of youth". With aging, dysregulation of food intake accompanied by sarcopenia ('wasting of the flesh") occurs (2). A number of hormonal mechanisms are related to the physiological anorexia of aging (3). In particular, recent studies have suggested that alterations in circulating testosterone levels lead in males to increased leptin levels and thus to anorexia (4).Another area of intense interest in understanding the mechanisms of aging in humans has been the alterations that occur in glucose metabolism with aging and the role of age-related glucose end products (AGE) in accelerating the aging process (5). This area has been closely linked with the changes in nutrition that occur with aging, with insulin resistance, and more recently, with the genes that encode for the insulin receptor. It is of interest that the hormonal changes produced by dietary restriction in rodents are similar to the agerelated hormonal changes in humans, as shown in Table 2 (6). This raises the possibility that these hormonal changes are protective, i,e. slow down metabolism and thus slow down the aging process. This creates a "chicken or egg" hypothesis, illustrated in Figure 1, which asks the question: do aging changes occur because of the decline in hormones or do high hormone levels produce aging changes?This review will briefly examine the available data in each of these areas and...

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The gerontogenes age‐1 and daf‐2 determine metabolic rate potential in aging Caenorhabditis elegans

Cited by 141 publications

References 6 publications

Interpreting interactions between treatments that slow aging

Interpreting interactions between treatments that slow aging

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

Endocrine and metabolic changes in human aging

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