Mitochondria and aging

2012 senior Scholar Award in aging

Mitochondrial DNA quality control and aging: promoting selective removal of mutant mitochondrial genomes Mitochondria are present in almost all cells, and contain many copies of a small, circular genome (mtDNA). The encoded gene products are all required, directly or indirectly, for oxidative... >> MORE

2011 senior Scholar Award in aging

A major challenge in basic research on aging is to distinguish among various potential causative influences of age-related diseases. There have been many hypothesis put forward to explain the deterioration of tissue homeostasis and regenerative capacity during aging. Age-induced accumulation of... >> MORE

2010 senior Scholar Award in aging
The role of mtDNA mutations in the aging process has been debatable for decades since Harmanís seminal work on mitochondria, oxidative stress and aging. Currently more than ever the field is plentiful in evidence both in favor and against an involvement of mtDNA mutations in aging, which have led... >> MORE
2010 senior Scholar Award in aging
It seems self-evident that babies are born young, independent of the age of their parents. However, this process poses a challenge to anyone thinking about the biological basis of aging. How does a mother whose cells have aged for 20, 30, or 40 years produce a baby with a whole lifetime ahead of... >> MORE
2010 senior Scholar Award in aging
This project will investigate a key paradox involving the potential role of mitochondria in aging. Historically, studies in mammals have shown that preservation of mitochondrial function and reduced generation of reactive oxygen species are correlated with increased lifespan and healthspan, i.e.,... >> MORE
2009 senior Scholar Award in aging
Aging is widely considered to involve a progressive loss of function of mitochondria, the cellular organelles that generate most of the energy required to sustain life. The notion that such mitochondrial dysfunction is not just a consequence, but a cause of aging is the basis of the mitochondrial... >> MORE
2009 senior Scholar Award in aging

Mitochondria are cellular organelles that use the oxygen we breathe to oxidize carbohydrates, fats and proteins. The oxygen is fully reduced to form water, and energy is released. The mitochondria capture this energy to phosphorylate ADP to ATP, a molecule that can be hydrolyzed by the cells to... >> MORE

2009 senior Scholar Award in aging

The cause of Alzheimer disease (AD), the most common neurodegenerative disorder of aging, is unclear. It is known that there is an increased accumulation of various proteins in the brain of AD patients (in so-called "amyloid plaques" and "tangles") that are clearly associated... >> MORE

2009 senior Scholar Award in aging

Mitochondria provide the cell with the energy they need to run on, but damaged mitochondria can be highly deleterious to cells. In a large cell like a neuron, getting the right number of mitochondria to the right part of the cell to provide for its needs can be crucial to its health. Clearing... >> MORE

2006 senior Scholar Award in aging
A major model of aging postulates that DNA mutations accumulate within mitochondria as we age. Mitochondrial DNA (mtDNA) is particularly vulnerable, because mitochondria are a major source of reactive oxygen species, small molecules that can damage DNA. This damage causes mtDNA mutations, whose... >> MORE
2006 senior Scholar Award in aging
Cellular energy is derived ultimately from the food we ingest. In order to be useful to the cell, food components such as proteins, lipids, and carbohydrates are eventually broken down into molecule-sized components. Through the process of "glycolysis," an individual cell converts carbohydrate... >> MORE
2005 senior Scholar Award in aging
Mitochondria are intracellular organelles responsible for metabolism as well as many biosynthetic pathways. Mitochondria are the source of much of the cellís energy and are also the major source of production of reactive oxygen species. Mitochondria contain their own distinct genome and, although... >> MORE
2005 senior Scholar Award in aging

For unknown reasons, individuals with the metabolic syndrome frequently have high blood pressure, increased blood lipids, reduced exercise capacity, oxidative stress, increased inflammation, glucose intolerance (diabetes), premature cardiovascular disease (atherosclerosis, heart attack and... >> 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
One of the characteristics of aging is progressive deterioration of muscle function. We will study this phenomenon using the fruit fly, Drosophila, as a model organism. Drosophila flight muscle is among the most metabolically active tissues in any organism. Its mitochondria, the... >> MORE
2001 senior Scholar Award in aging

The theory known as the "free radical theory of aging" has achieved prominence as one of the most compelling explanation for many of the degenerative changes of aging. Ongoing researches in the study of free radical biochemistry and in the genetics of aging have been at the forefront of this... >> MORE

2000 senior Scholar Award in aging

Recently, the use of a novel approach for specific detection of heteroplasmic mutations in mitochondrial DNA (mtDNA) has surprisingly revealed high copy point mutations (present in up to 50% of mtDNA) at specific positions in the control region of human fibroblast mtDNA from normal old, but not... >> MORE

1999 senior Scholar Award in aging
Research Interests. Our major interest is the decay of mitochondria with age due to the oxidative damage of mtDNA, proteins, and lipids. We are making progress in reversing some of this mitochondrial decay in old rats by the feeding of normal mitochondrial metabolites at high levels; we now... >> MORE
1999 senior Scholar Award in aging
Accurate copying of DNA in cells is carried out by DNA polymerases. These enzymes polymerize nulceotides that are complementary to the nucleotides in the cellular DNA template, yielding daughter DNA molecules that preserve the nucleotide sequence of the parental molecules. Errors in this process,... >> MORE
1999 senior Scholar Award in aging
Mitochondria have been proposed by others to be both initiators and targets of cellular degeneration associated with aging. The proposed work is designed to test specific hypotheses in which cellular degradation and aging are related to mitochondrial mutation. Measurement and implications of... >> MORE
1999 senior Scholar Award in aging

Evidence continues to accumulate that aging is associated with a decline in mitochondrial function, suggesting that mitochondrial dysfunction maybe a major factor in the pathophysiology of aging and senescence. The mitochondria provide most of the cellular energy through oxidative... >> 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

2013 new Scholar Award in aging

In the next 50 years, the world's population aged 60 and over will more than triple from 600 million to 2 billion and carries the risk of significant social and economic burden if healthy aging cannot be maintained. Current research on aging has largely focused the molecular mechanisms of age-... >> MORE

2013 new Scholar Award in aging

Mitochondria produce the energy needed for cellular growth and activity. Decline in mitochondrial form and function are widely recognized but poorly understood features of aged cells, and key features of aging-related diseases such as Parkinson’s and Alzheimer’s. My long-term goal is to identify... >> MORE

2012 new Scholar Award in aging

The mechanisms which impact aging and aging-related diseases are complex and challenging to study. Systems-biology studies have mapped out aging-related genetic networks, but these top-down approaches are complicated by the difficulty of distinguishing correlations from causality. Genome-wide... >> MORE

2011 new Scholar Award in aging

Aging occurs as cellular structures and function degenerate over time. Mitochondria are essential cellular organelles required for energy production, numerous biosynthetic processes as well as the regulation of programmed cell death. However, mitochondrial dysfunction is associated with aging as... >> MORE

2011 new Scholar Award in aging

Mitochondrial dysfunction is a pathological hallmark of aging-dependent human diseases such as cardiovascular disorders, cancer, stroke and neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease. While numerous genetic and environmental risk factors are known to... >> MORE

2010 new Scholar Award in aging
Age-related declines in muscle mass and strength contribute significantly to falls, frailty and losses of mobility and independence ñ events which concern many older Americans. Of the many factors which contribute to muscle aging, our work has focused on mutations of the mitochondrial genome and... >> MORE
2009 new Scholar Award in aging
Some of the effects of aging are thought to originate from cell structures called mitochondria. Mitochondria are the cells' power sources; hundreds to thousands are present in every cell of the body, and each contains its own DNA that is separate from the cell nucleus, where the majority of our... >> MORE
2009 new Scholar Award in aging

Emerging evidence suggests that excessive fat oxidation can be detrimental to whole body insulin sensitivity and mitochondrial performance. In our recent studies, diet-induced metabolic dysfunction in obese rodents was specifically linked to elevated rates of ìincompleteî... >> MORE

2009 new Scholar Award in aging
Mitochondria are cytoplasmic organelles that generate the majority of cellular energy and carry out numerous other critical biochemical processes. Mitochondrial dysfunction is implicated in a vast array of severe diseases, including age-associated afflictions; indeed reactive oxygen species... >> MORE
2008 new Scholar Award in aging
The free radical theory of aging was proposed by Denham Harman more than 50 years ago, and has been perhaps the most actively studied mechanistic theory of aging. It is based on the idea that oxygen free radicals, in particular mitochondrial superoxide, are normally generated within cells, yet are... >> MORE
2008 new Scholar Award in aging
The mechanisms that cause the deterioration of cellular functions during the aging process remain poorly understood. Alterations in mitochondrial energy metabolism may be particularly important because it affects a wide range of cellular processes, and any defect will have widespread consequences... >> MORE
2007 new Scholar Award in aging
Calorie restriction (CR) extends lifespan in model organisms including yeast, flies, worms and rodents. Changes in NAD+ metabolism and a family of conserved NAD+ -dependent protein-modifying enzymes called sirtuins are involved in mediating the longevity response to CR. The... >> MORE
2006 new Scholar Award in aging

The mitochondrial respiratory chain has multiple components (complexes I-V and coenzyme Q) that work intimately together to turn fuel (supplied by the metabolic breakdown of sugar, fat, and protein) into energy (in the form of ATP). It is also a site of production of free radicals, which are... >> MORE

2006 new Scholar Award in aging
Why do we age? Although no one knows for certain, there are many theories that offer potential explanations. One such theory is called the mitochondrial theory of aging. Mitochondria are small sub-cellular organelles that harvest energy for our bodies by combining the electrons from our digested... >> MORE
2006 new Scholar Award in aging

Mitochondria play a central role integrating cellular energetics and the control of cell survival. As a result they are a critical element in aging and many degenerative diseases. Our research focuses on identifying the role of in vivo mitochondrial dysfunction in degenerative diseases... >> MORE

2004 new Scholar Award in aging

The decline in energy with age highlights energy metabolism and the role of mitochondria in aging. Aged cells accumulate oxidative DNA damage that is likely to be responsible for the observed increase in mutations, particularly in the mitochondrial genome. The major source of reactive oxygen... >> MORE

2002 new Scholar Award in aging
The overall goal of this study is to isolate mitochondrial DNA (mtDNA) mutations associated with aging, to analyze the accumulation of the mutations during aging and to determine the genetic and functional consequences of the age-dependent mtDNA mutations in mouse. In mammalian cells, over 90% of... >> MORE
2000 new Scholar Award in aging
Mitochondria are the organelles within cells that are responsible for generating much of the required energy for cell survival. Mitochondria have their own DNA (mtDNA) which encodes some of the necessary proteins to carry out these biochemical reactions. Recently, there has been an increased... >> MORE