S M Jazwinski

..However, this will require the development of indices of frailty and of healthy aging. In the end, we may be able to 'cure' aging, but only in a statistical sense which is measured at the level of the population...

..This element of chance provides opportunities for an integrative approach, which is beginning to appear in yeast aging research...

..This expectation was confirmed, providing new avenues for exploring causal factors in yeast aging. The methodology described here can be readily applied to other aspects of aging in yeast and in higher organisms...

..Phenomena that resemble the retrograde response appear to exist in human cells, with both common and cell type-specific gene expression changes as the output...

..Although the retrograde response and caloric restriction are distinct pathways of life span extension, there appears to be some overlap of the longevity effectors under their control...

..Common threads weave their way through the studies of aging in yeast and in other model organisms. This suggests conserved features of aging across phyla...

..Both compensatory and preventive mechanisms determine life span, while epigenetic factors and the element of chance contribute to the role that genes and environment play in aging...

..Gene regulatory phenomena akin to the retrograde response also operate in human cells, which display both common and cell-type specific changes in gene expression on loss of mitochondrial function...

..The results raise the possibility that the RAS genes and mitochondria may play a role in the epigenetic inheritance of reduced mortality rate afforded by transient, mild heat stress...

..Since RAS2 is known to down-regulate stress responses, this demonstrates that for longevity the ability to recover from stress is at least as important as the ability to mount a stress response...

..We liken the senescence factor to the product of an anti-oncogene or tumor suppressor gene that neutralizes Ras...

..A gene deletion in haploid cells resulted in a pronounced increase (approximately 50%) in mean and in maximum life span. These results indicate that this gene, which we call LAG1, plays a role in determining yeast longevity...

..From the known patterns of gene expression elicited by rpd3delta, hda1delta, and sir2delta, we propose that the major longevity effectors of caloric restriction in yeast involve carbohydrate/energy metabolism and mitochondrial function...

..This and its expression profile raise the possibility that it may be involved in neurodegenerative disease. This possibility suggests at least one way in which LAG1Hs might be involved in human aging...

..The functions of RPD3 and HDA1 do not overlap entirely. RPD3 exerts its effect on chromatin at additional sites in the genome, raising the possibility that events at loci other than rDNA play a role in the aging process...

..Silencing of ribosomal DNA appears to be of particular importance. Extrachromosomal ribosomal DNA circles are neither sufficient nor necessary for yeast aging...

..Finally, protein synthesis is a third aspect, which depends on the transcriptional state of chromatin and the histone deacetylases that modulate it...

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..These population genetic studies can be augmented by mechanistic studies in transgenic mice...

..There is evidence that this age change plays a causal role. Aging possesses features of a nonlinear process, and it is likely that application of nonlinear system methodology to aging will be productive...

..As a consequence, the study of yeast aging may be helpful in understanding processes occurring in the aging brain...

..The urgency for such studies is great: The population is graying, and this research holds the promise of improvement in the quality of the later years of life...

..Because of its complexity, the aging process takes us into the realm of integrative biology, and thus, biogerontology should prove instrumental in deciphering the functional and regulatory circuitry of the sequenced genome...

..Thus, RTG2 lies at the nexus of cellular metabolism and genome stability, coordinating two pathways that have opposite effects on yeast longevity...

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..Experimental evidence in support of this model is presented that spans the levels of population mortality rates, cellular spatial organization, and gene dysregulation...

..The novel function of Pex6p described here may provide insights into peroxisomal and mitochondrial disorders and into metabolic diseases in general...

..These expression changes may help explain the response of different tissues to the loss of mitochondrial function due to aging or disease...

..These preliminary results show that the proteomics approach can be used to identify potential proteins or markers that may be involved in the aging process and/or be important determinants of longevity...

..This aggravation of the initial damage is ameliorated by the suppression of the production of mitochondrial proteins in the absence of Ras2p signaling of mitochondrial biogenesis...

..The RAS genes have emerged as important modulators of life-maintenance processes and of life span itself...

..These gene regulatory events portend an increase in the generation of biosynthetic intermediates necessary for the production of daughter cells, which is the measure of yeast replicative life span...

..Rtg2p and Gcn5p in the SLIK complex link metabolism to stress responses, chromatin-dependent gene regulation, and genome stability in yeast aging...

..Homologues of Lag1p have been identified in higher eukaryotes, including human, raising the possibility that ceramide and other sphingolipid metabolites play a wider role in biological aging...

..In sum, it is clear that mitochondria lie at the nexus of yeast longevity and aging...

..We propose, more generally, that age asymmetry depends on partition of active and undamaged cellular components to the progeny and that this "filter" breaks down with age...

..In conclusion, these data suggest an important role for LASS1/C(18)-ceramide in gemcitabine/doxorubicin-induced cell death via the activation of caspase-9/3 in HNSCC...

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..This provides a wide range of physiologic processes through which Lag 1 p may impinge upon life span...

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..B) Is there a correlation between other suspected risk factors, hypertension and obesity, and p53 gene mutation prevalence and spectrum? (C) Is there a correlation between survival and p53 gene mutation prevalence and spectrum? ..

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..The results of the proposed research have important implications for aging, diabetes, and cancer. ..

..The results of the proposed research have important implications for aging, diabetes, and cancer. ..