Genes and Aging

2012 senior Scholar Award in aging

Lifespan varies considerably among mammals; the mechanisms of this old and fundamental observation in aging research remain somewhat mysterious. Understanding the process at the cellular and molecular level may lead to interventions that can prolong lifespan in general and thus prolong life in... >> MORE

2012 senior Scholar Award in aging

The use of simple model organisms for aging such as yeast, worms and flies has driven the aging field forward and been instrumental for the identification of cellular pathways that modulate the aging process. From work in my lab and many others, a set of conserved aging genes have been... >> MORE

2012 senior Scholar Award in aging

Aging research in model organisms has revealed three major biochemical pathways that influence longevity across species. These three pathways (insulin/IGF1, AMPK, and mTOR) have the shared features that they are controlled by the nutrient status of the organism, which can likewise impact the... >> MORE

2012 senior Scholar Award in aging

While the heritable material, DNA, contains the blueprint that is necessary for the development of an organism, the execution of this blueprint (and what determines our cellular diversity) is controlled by complex machinery that determines which regions of DNA are utilized by the cell, a... >> MORE

2011 senior Scholar Award in aging

Our research into the relationship between body temperature and longevity was stimulated by two related observations in animal systems. It has been known for almost fifty years that dietary caloric restriction in many species (including primates) could extend life. In the course of those... >> MORE

2011 senior Scholar Award in aging

There is a well-documented association of aging with increased incidence of diabetes and cancer, as well as reduced capacity for wound healing and tissue repair. In studies aimed at understanding how cancer genes are regulated in stem cells, we unexpectedly discovered a role for an ancient... >> MORE

2011 senior Scholar Award in aging

The intestine is maintained by stem cells that require a cellular neighborhood, or niche, consisting of Paneth cells. The intestine undergoes significant decline in function and regeneration with age, but it is unclear whether these age-related changes are due to direct changes in stem cells or... >> MORE

2011 senior Scholar Award in aging

We are interested in determining the mechanisms underlying age-related declines in tissue homeostasis and repair. Following embryogenesis, most animals undergo a dramatic period of growth, during which the body, and all its component parts, increase in size and mass. On reaching adulthood, net... >> MORE

2010 senior Scholar Award in aging
The nematode C. elegans has proven to be an invaluable model organism for identifying mechanisms that influence longevity, and may be conserved across species. Recently considerable interest has been focused on how aging is influenced by the target of rapamycin (TOR) signaling pathway. TOR... >> MORE
2010 senior Scholar Award in aging
Only a handful of interventions are known to extend lifespan in mammals. Among these, dietary restriction is the best established. In a recent study by Harrison and others, rapamycin was the first drug demonstrated to increase mammalian lifespan. However, all known interventions that affect aging... >> MORE
2010 senior Scholar Award in aging
Studies in the roundworm C. elegans have been very fruitful in uncovering the gene families that are able to influence aging in different organisms, including mammals. In addition to the genetic code itself, how the genetic materials are packaged in the cell, i.e. how the DNA is wound up by... >> MORE
2010 senior Scholar Award in aging
We have developed two new model systems that lead to significant increases in mouse maximal longevity. One uses a "Crowded Litter" (CL) approach to reduce food availability, but only in the first 3 weeks of life. The other involves genetic ablation of the gene for MIF, a pro-inflammatory cytokine... >> MORE
2010 senior Scholar Award in aging

With the support of this award we will apply two "Next Generation" approaches to the study of genetic mouse models in which specific steps of TORC1 signaling (i.e., via the mTOR/raptor complex itself or the downstream proteins 4EBP1 and S6K1) are selectively altered in key young and... >> MORE

2009 senior Scholar Award in aging

Aging remains one of biology's most confusing and contentious subjects. That is, how a trait as deleterious as senescence, with death as its implicit endpoint, could be the product of natural selection. Many biologists have taken the view that senescence reflects an inevitable process of damage... >> MORE

2009 senior Scholar Award in aging

Aging is associated with widespread but subtle changes in gene expression. We and others have discovered that one of the drivers of the age-dependent gene expression programs in mammals is the stress-responsive transcription factor NF-kB. For instance, both molecular and cellular features of... >> MORE

2009 senior Scholar Award in aging
The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, the naked mole-rat has extraordinary resistance to cancer as tumors have never been observed in these rodents. The mechanism for cancer resistance in the naked mole-rat is... >> MORE
2009 senior Scholar Award in aging
The major goal of our program is to identify aging genes in the mouse and then to test those genes in humans. The testing in humans will be carried out in collaboration with Dr. Joanne Murabito of Boston University, who will test these genes in individuals who have lived to at least 90 years of... >> MORE
2008 senior Scholar Award in aging
Naked mole-rats can live over 28 years, significantly longer than similar-sized rodents like mice that do not commonly live more than 4 years. Naked mole-rats also appear to be very resistant to neoplasia. Because of these marked differences in longevity and age-related phenotypes between such... >> MORE
2008 senior Scholar Award in aging
Over the last decade we have made remarkable progress in identifying genes that have large effects on longevity within laboratory organisms. Do differences in these genes lead to the differences in longevity that we observe from individual to individual? Understanding variation in aging within... >> MORE
2007 senior Scholar Award in aging

Hormones are well known to coordinate animal metabolism, reproduction, and homeostasis to maximize survival and reproductive success. Pioneering work in the small roundworm Caenorhabditis elegans has revealed that several hormones also impact animal longevity. Nuclear hormone receptors... >> MORE

2007 senior Scholar Award in aging
Remarkable progress in genomic research is leading to a complete map of the building blocks of biology. Knowledge of this map is, in turn, fueling the study of gene regulation, where proteins often regulate their own production, or that of other proteins, in a complex web of interactions. An... >> MORE
2007 senior Scholar Award in aging
For over 70 years it has been known that animals such as mice and monkeys have internal defense systems that fend off common diseases such as cancer, diabetes, heart disease and neurodegeneration. In the past five years researchers have discovered genes that underlie the CR response but this is... >> MORE
2007 senior Scholar Award in aging

The roundworm Caenorhabditis elegans (C. elegans) has been a very successful model organism in biomedical science for more than 30 years. An abundance of biological insights have been obtained using this relatively simple animal. For instance, studies on the insulin signaling pathway... >> MORE

2006 senior Scholar Award in aging

Naked Mole Rats (NMRs) are the longest-living rodents known; they live >28y in captivity which is ~9x longer than similarly-sized mice. NMRs show attenuated age-related declines in both morphology (e.g. bone loss) and function ( e.g. vascular function). Furthermore, we have never seen any... >> MORE

2006 senior Scholar Award in aging
The discovery of genes that positively or negatively affect how long an organism lives has been a tremendous advance in the science of aging. While numerous genes have been isolated that affect the longevity of organisms like worms and flies, to date, there have been relatively few genes that... >> MORE
2006 senior Scholar Award in aging

Aging is observed in all animal species. Studies in vertebrates, insects, nematodes and yeast suggest that conserved biochemical and genetic pathways are involved in lifespan regulation. For example, insulin signaling and sirtuin activity have dramatic effects in longevity across species.... >> MORE

2006 senior Scholar Award in aging

Recent advances in genetic mapping techniques have made possible the identification of chromosomal regions in which there are aging-relevant ìquantitative trait lociî (QTLs)--genes that influence aging processes but that are, as yet, not specifically identified. Most current... >> MORE

2006 senior Scholar Award in aging
We sense aging as something that happens to our bodies, but as scientists we know that the underlying causes lie in the subtle, and sometimes not so subtle, changes that go on in our cells. We also know that these changes are complex and that they progress in many tissues. As yet, no one has... >> MORE
2006 senior Scholar Award in aging
Changes in gene expression in aged adults across species do not solely seem to be implemented in response to mounting cellular damage; rather, conserved, developmentally-timed transcriptional regulation during young adulthood seems to control features of aging. For example, early adult C.... >> MORE
2005 senior Scholar Award in aging

It is well known that advanced maternal age increases the risk of giving birth to children with Down syndrome, and a significant effort has been made to understand the molecular basis of this increased risk. What is less well known is that advanced paternal age is also associated with an... >> MORE

2005 senior Scholar Award in aging

Model organisms, whether they are yeast, worms, fruit flies, mice, and even animal cells in tissue culture, have proven a fertile ground for discovery of factors, genetic and environmental, that impinge upon the biological aging process and determine life span. Some of these factors make their... >> MORE

2005 senior Scholar Award in aging

My laboratory has been focused on elucidating the function of the Klotho gene. The Klotho gene was originally identified as a gene mutated in a mouse strain that exhibits a syndrome resembling human aging, including a shortened lifespan, skin atrophy, muscle atrophy, neuronal... >> MORE

2004 senior Scholar Award in aging

Addressing the health problems of the aged by exploiting experimentally manipulable animal models
The rapidly growing elderly population inevitably confronts an increased risk for several debilitating diseases, cognitive decline, and virtually certain loss in muscle... >> MORE

2004 senior Scholar Award in aging

Apolipoprotein E (apoE) is a cholesterol-carrier in the blood with genetic variants that influence the risk of Alzheimerís disease and vascular disease. During human evolution, the apoE gene has changed importantly from the gene shared by human-chimpanzee ancestors 5 million years ago.... >> MORE

2004 senior Scholar Award in aging

The roundworm Caenorhabditis elegans has proven to be an excellent organism for genetic studies of longevity, and many genes known to affect lifespan have been identified and characterized in this organism. Nonetheless, much remains to be discovered about the genetic, molecular and... >> MORE

2004 senior Scholar Award in aging

Aging is accompanied and perhaps even defined by a gradual loss in the ability of the organism to respond successfully to fluctuations in the environment and maintain homeostasis. We have discovered that altered activity of the tumor suppressor p53 accelerates this process in the mouse. The... >> MORE

2004 senior Scholar Award in aging

From invertebrates to mammals, diet restriction can extend lifespan and slow symptoms of aging. How diet restriction affects senescence, however, remains a mystery that is at the heart of much current molecular and genetic research. One attractive explanation holds that when animals are diet-... >> MORE

2003 senior Scholar Award in aging
Aging occurs in almost all organisms, yet the molecular basis of aging is poorly understood. In addition, many diseases, including cancers, occur much more frequently in aged populations. Therefore, an understanding of the molecular and cellular events that accompany aging would undoubtedly... >> MORE
2003 senior Scholar Award in aging

The aging of an organism is determined by its genetic background and is influenced by environmental inputs. Genetically, aging is considered to be a polygenic process; however, studies in model systems revealed mutations in single loci that extend life span. The best established epigenetic... >> MORE

2003 senior Scholar Award in aging

The aging process is increasingly considered to be a programmed event regulated by individual gene products, like other developmental processes. One major implication of this working model is that several diseases associated with aging might actually be linked by a common set of aging genes... >> MORE

2002 senior Scholar Award in aging

Aging is among the most universal of biological processes and perhaps also among the most mysterious. Numerous age-related changes are apparent at the organismic level, but we are only now starting to understand age-related changes at the molecular level. Oxidative damage, replicative... >> MORE

2002 senior Scholar Award in aging
Mutational screens in C. elegans and D. melanogaster demonstrate that single gene mutations can extend life span. The phenotypes associated with these mutations include reduced insulin and/or insulin-like growth factor signaling and increased resistance to oxidative and other life-... >> MORE
2002 senior Scholar Award in aging
Most of what we know about the genetics of aging comes from four organisms well-adapted to life in the lab--yeast, nematodes, fruit flies and mice. These are powerful model systems, but not without problems. Previous studies have shown that organisms maintained in the lab often evolve increased... >> MORE
2001 senior Scholar Award in aging

The nematode Caenorhabditis elegans is an excellent model for genetic studies of the aging process. Mutations in the clk-1 gene of C. elegans result in an extended life span, slowed development and sluggish behavior. Our studies of the clk-1 mutants suggest that the slowed rates of aging,... >> MORE

2001 senior Scholar Award in aging
Single gene mutagenesis is a powerful method for dissecting complex biological phenomena such as aging. It has been used with great success in developmental biology. One advantage, for aging research in particular, is that it does not require detailed knowledge of the mechanisms that control life... >> MORE
2001 senior Scholar Award in aging

Generalized aging at the cellular level is thought to arise from the accumulation of damage to protein and nucleic acids that eventually results in the impairment of normal cellular function or transformation of the cells to a cancerous form of growth. How does this damage occur? One hypothesis... >> MORE

2000 senior Scholar Award in aging
Despite evidence for a substantial genetic component, the inherited factors that define life span (longevity) in humans remain unknown. The overall objective of this proposal is to identify chromosomal loci (and ultimately genes) that influence longevity and longevity-related traits in humans, and... >> MORE
2000 senior Scholar Award in aging
C. elegans is an ideal model organism for exploring the mechanisms that determine lifespan. It is short-lived, its genome has been sequenced, and its utility for studying aging has been demonstrated by previous studies. Moreover, because similar molecular strategies are often used in C... >> MORE
2000 senior Scholar Award in aging
The availability of extensive genomic sequence, EST databases, and DNA chip technology opens unprecedented opportunities to precisely define the gene expression profiles of different types of cells. To wit, it is now possible to accurately compare mRNA populations expressed in different cells by... >> MORE
1999 senior Scholar Award in aging

Evidence that oxidative damage, a by-product of normal metabolism in virtually all animals, is causally involved in the process of aging and the development of degenerative disease has been steadily accumulating for more than forty years. An understanding of the exact nature of this damage to... >> MORE

1999 senior Scholar Award in aging

Few mammalian models of aging have the phenotype of increased life span. Virtually all work has focused on food restricted (FR) rodents. Although many changes in physiologic function and gene expression have been identified, it is difficult to determine which changes contribute... >> MORE

1998 senior Scholar Award in aging
Animals with longer lifespan usually have higher resistance to stress. The extended-lifespan Drosophila mutant methuselah resists all three different stresses tested, heat, starvation, and paraquat, an oxygen free radical generator. This suggests a molecular approach to identifying... >> MORE
1998 senior Scholar Award in aging
Subjects who can comfortably reach very old ages may have an advantageous consatellation of genes, giving them resistance to many causes of stress and disease, or may simply have one or more genes affecting the duration of their life. Such longevity genes have been observed in other organisms. The... >> MORE
1998 senior Scholar Award in aging
Dr. Guarente is extending his studies of genetic mechanisms of aging in yeast to mammals. He intends to determine changes in rDNA that accumulate with age in mice. He will then generate transgenic mice with specific rDNA changes in order to test whether specific changes cause aging. >> MORE
1998 senior Scholar Award in aging
In previous research, Dr. Johnson identified gerontogenes (genes that specify length of life) in the nematode worm C. elegans. Dr. Johnson now proposes to search for such genes in mice using Recombinant Inbred line and by stress induced mutagenisis. >> MORE
1998 senior Scholar Award in aging
Dr. Kenyon believes that the study of short-lived mutants of C. elegans may lead to the identification of important life-span regulating genes. She proposes to identify such genes. She will also import human genes into C. elegans short-lived mutants in order to see which of theses genes best... >> MORE
1998 senior Scholar Award in aging

Three human families with clusters of extremely long-lived individuals will be analyzed in order to identify specific genes responsible for extreme longevity.

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1998 senior Scholar Award in aging
Dr. Ruvkun has previously shown that an insulin-like signaling pathway regulates longevity and metabolism in C. elegans. The most important output of this pathway in C. elegans is the transcription factor DAF-16. Dr. Ruvkun now proposes to search for the downstream targets of DAF-16 in order to... >> MORE
2013 new Scholar Award in aging

In the United States, only about one person in 5,000 achieves an age of 100 years or more. Demographers and epidemiologists have estimated that the length of human lifespan is a moderately heritable trait, with the offspring of individuals achieving old age being more likely to also achieve old... >> MORE

2013 new Scholar Award in aging

Mitochondrial dysfunction is a hallmark of aging phenotypes and aging-related diseases, such as cancer, neurodegenerative diseases and cardiovascular disease. Healthy, functioning mitochondria require the coordinated expression of genes located on both the nuclear and mitochondrial genomes.... >> MORE

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