Maintenance and repair of proteins and organelles

2012 senior Scholar Award in aging

C. elegans research has made profound contributions to the fields of aging, health and disease. In particular, genetic analysis in C. elegans has identified components of major signaling pathways that underlie diseases of aging such as cancer and Alzheimer's disease, and revealed... >> MORE

2012 senior Scholar Award in aging

This project seeks to understand the nature of a material called “aging pigment”, referred to as lipofuscin (“lipo-fusin”), that accumulates in the lysosomes of neurons of normal animals. Lysosomes are small membrane-bounded sacs that contain a high concentration of degradative enzymes that... >> MORE

2012 senior Scholar Award in aging

Aging is associated with increased dysfunction in our immune systems. Consistent with this, there is a persistent low-grade inflammation as indicated by the increased concentrations of circulating inflammatory cytokines and chemokines in elderly populations. How aging leads to the decline in our... >> MORE

2011 senior Scholar Award in aging

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that constitutes the major cause of neurological motor impairment in the elderly and as such places an extraordinary burden on the US health care system, at an estimated cost of $25 billion annually. The major risk factor for... >> MORE

2011 senior Scholar Award in aging

Autophagy (self-eating) is an important catabolic process that contributes to cellular energy, and helps to protect cells by delivering damaged organelles and potentially toxic protein aggregates to the lysosome for degradation. Autophagy declines with age and is thought to accelerate aging... >> MORE

2011 senior Scholar Award in aging

Proteins must achieve their correct three-dimensional folded structure in order to carry out their cellular functions. Failure to fold its proteins can be catastrophic for cells, since misfolded proteins can aggregate into toxic amyloid species. Aging is universally associated with a decline in... >> MORE

2011 senior Scholar Award in aging

Aging and stress, stress and aging - a pair of ominous conditions that can affect the quality of life. When events go awry, the cellular machinery senses molecular damage and compensates by induction of protective cellular stress responses. Aging, however, compromises the robustness of these... >> MORE

2010 senior Scholar Award in aging
Loss of muscle mass and degeneration of the fibers that make up skeletal muscle, a condition called sarcopenia, are major hallmarks of aging. Muscle loss and degeneration contribute to many other ill-effects of aging including frequent bone fractures and insulin resistance, a pre-diabetic condition... >> MORE
2010 senior Scholar Award in aging

Organisms have evolved molecular machines to help newly synthesized proteins fold properly and also to eliminate mature proteins once they are recognized as damaged or misfolded. Many studies have shown that, as they age, cells become less efficient at recognizing and degrading damaged or... >> MORE

2009 senior Scholar Award in aging
Changes in gene activity are part of the cellular aging process, however, the mechanisms that cause age-related alterations in gene expression are poorly understood. We have recently discovered that nuclear pore complexes (NPCs), essential multiprotein channels that mediate molecular trafficking... >> MORE
2009 senior Scholar Award in aging
This proposal is to study the role of RIP1 kinase and its signaling pathway in mediating production of an important pro-inflammatory cytokine, TNFα, and its implication in aging. Increased levels of TNFα during aging are detrimental for longevity by contributing to the pathogenesis of... >> MORE
2008 senior Scholar Award in aging
A cell can divide to produce two sister cells with different lifespans. One reason for this difference in lifespan potential may be because one of the cells inherits an unequal share of toxic, damaged proteins. This process has been characterized in budding yeast, in which oxidatively damaged... >> MORE
2008 senior Scholar Award in aging

Aging is no less than war waged between chemistry and biochemistry. Chemical reactions result in widespread spontaneous damage to the biomolecules essential for life. However, biochemical reactions can limit or even reverse this damage. Understanding the ability of organisms to mount... >> MORE

2007 senior Scholar Award in aging
Aging is associated with a large increase in the incidence of cancer. One possible cause that has not yet been investigated is that age-related cancer may be due to abnormalities in the degradation of proteins that regulate cell division. Cell division is normally controlled by oscillations in... >> MORE
2006 senior Scholar Award in aging
The research in my laboratory concerns aspects of quality control in protein synthesis. The failure rate in protein synthesis is substantial, which necessitates a reliable means of disposal for these error-containing and therefore unwanted proteins. The risk associated with accumulation of... >> MORE
2004 senior Scholar Award in aging

The goal of these studies is to clarify the molecular mechanisms for two prominent features of aged organisms: 1) the accumulation of abnormal proteins in cells, and 2) the marked, debilitating loss of muscle mass (sarcopenia). To understand these phenomena, we shall build upon recent advances... >> MORE

2004 senior Scholar Award in aging

It has been thought for over 100 years that an understanding of the cause of an early onset premature aging disease called Hutchinson-Gilford Progeria Syndrome (HGPS), would provide insights into normal human aging. Progeria is an extremely rare disease that was recently found to be caused by... >> MORE

2004 senior Scholar Award in aging

Approximately 10% of individuals over age 65, and nearly half of those over age 85, suffer from Alzheimer's disease. Parkinson's afflicts 1% of people over age 60 and the risk of contracting the disease increases with age. Currently, approximately 4.5 million Americans have Alzheimer's, and more... >> MORE

2004 senior Scholar Award in aging

The work by my laboratory at the California Institute of Technology is about understanding bits and pieces of the following large problem: how and why cells destroy their own proteins? A related problem is to understand the consequences of having protein destruction machines in every cell of... >> MORE

2003 senior Scholar Award in aging

Aging is invariably associated with reduced neurological function. Moreover, the incidence of acute neurodegenerative disease strongly increases with age. As the average lifespan lengthens due to improvements in medicine and public health, the incidence of devastating neurodegenerative diseases... >> MORE

2013 new Scholar Award in aging

The accumulation of misfolded proteins contributes to many diseases, ranging from disorders of the eye to neurodegeneration. These protein misfolding and aggregation diseases are strongly associated with aging, suggesting that older cells are unable to effectively clear damaged proteins.... >> MORE

2013 new Scholar Award in aging

Aging results in a decline in the integrity and function of cells and tissues.  One reason for this decline is thought to be the inevitable accumulation of misfolded and damaged proteins with time accompanied by the collapse in the cells’ protective protein quality control mechanisms to deal... >> 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

Tissues and cells are constantly bombarded by a complex array of environmental factors that can have deleterious effects on many critical cellular functions. The selective removal of damaged or otherwise non-functional proteins from the proteome is an essential task that is mediated by the... >> MORE

2012 new Scholar Award in aging

Neurons are highly specialized cells with very long projections called axons, which they use to communicate with one another. Neurons communicate with each other by transmitting signaling molecules. Some of these signaling molecules, and most of the machinery that stores and sends these signals... >> MORE

2012 new Scholar Award in aging

Lysosomes are responsible for the turnover and clearance from cells of damaged organelles and protein aggregates. Long-lived cells such as cardiomyocytes, retinal pigmented epithelial cells and neurons are particularly dependent of the efficient function of their lysosomes to prevent the... >> MORE

2012 new Scholar Award in aging

Sestrins are stress-inducible proteins that are found in most animal species. Sestrins have several biochemical roles against oxidative damage and abnormal synthesis of proteins and lipids, which can contribute to the attenuation of aging. Recently, using Drosophila (fruit fly) model organism,... >> 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

All organisms must maintain homeostasis when conditions change in order to survive. With age the ability to maintain homeostasis declines, making it more difficult to survive injury or illness. Impaired homeostasis may also contribute to the increased incidence of many diseases with age. The... >> 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
Maintenance of proper protein function (protein homeostasis) is critical and at the cellular level it is achieved by rigorous protein quality control, which involves mechanisms such as protein folding and protein degradation among others. It is well established that with age protein homeostasis... >> MORE
2010 new Scholar Award in aging
The recent realization that genes involved in protein quality control exert a major impact over life span has spurred efforts to investigate the relationship between protein homeostasis and aging.

Much remains to be learned about the involvement of protein turnover in nuclear envelopathies.... >> MORE

2010 new Scholar Award in aging
Aging is associated with an increased risk for cancer and neurodegenerative diseases. These diseases are often caused by a perturbation of the fine balance between protein synthesis, folding, localization, activity and turnover. For example, controlled protein turnover via the ubiquitin-proteasome... >> MORE
2010 new Scholar Award in aging
Autophagy, meaning self-eating in Greek, is an important pathway that eukaryotic cells use to degrade and recycle un-needed or harmful cellular contents. Autophagy has been found to decrease in aged cells and tissues, suggesting that the decline of autophagy may contribute to aging. In addition,... >> MORE
2009 new Scholar Award in aging
As cells age, they accumulate intracellular, misfolded protein aggregates. In contrast, young cells appear to be in a state of protein homeostasis in which the physical properties of individual proteins (e.g., their folding conformations) are properly maintained by quality control mechanisms (e.g... >> MORE
2009 new Scholar Award in aging
Cellular vitality depends upon the cellís ability to produce functional proteins that carry out important activities essential for life. The duration of a cellís life relies in great part on the cellís ability to maintain its critical cohort of proteins in their functional state. The key pathways... >> MORE
2009 new Scholar Award in aging
Cells are the building units for our bodies, and proteins are the chief actors within each cell. Among the many different macromolecules inside our cells, the vast majority are proteins, which carry out virtually all the biological functions within each cell. Hence, the well-being of cells... >> MORE
2009 new Scholar Award in aging
As life spans increase through improvements in medicine and public health, the prevalence of devastating nerve degeneration diseases will inexorably increase to become one of the most severe obstacles to living longer, more fulfilling lives. We are in urgent need of new concepts and approaches to... >> MORE
2008 new Scholar Award in aging
Alzheimer's, Parkinson's, and Huntington's diseases are caused by mutant forms of proteins prone to clumping, or aggregation. These diseases are strongly age-associated, suggesting that protein aggregates or the inability to resolve them may worsen with age. Even in cells that do not carry... >> MORE
2008 new Scholar Award in aging
The production of and degradation of cellular proteins is a tightly regulated process. Regulated protein degradation is critical for many cellular processes such as aging and cell growth. Even under normal conditions, up to 30% of all cell proteins fail to fold properly, and are immediately... >> MORE
2008 new Scholar Award in aging

Age and obesity are two factors that predispose individuals to Type II diabetes. Although the connection between obesity, age and the onset of Type II diabetes is well recognized, the molecular basis for it remains elusive. My laboratory studies the molecular mechanisms that may explain the... >> MORE

2007 new Scholar Award in aging
Adult onset neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS) or Huntington's disease, don't present clinical symptoms until late in life suggesting that the normal aging process plays an important role in determining when affected individuals begin to show disease symptoms.... >> MORE
2007 new Scholar Award in aging

Studies in model organisms such as C. elegans have provided significant insight into the molecular mechanisms underlying aging. The insulin-like daf-2 signaling pathway and dietary restriction regulate aging in C. elegans and other species. However, their downstream... >> MORE

2007 new Scholar Award in aging

A major problem during chronological aging is the accumulation of oxidative damage to cellular macromolecules produced by mitochondria-generated reactive oxygen species (ROS). Young cells are protected by a balanced activity of the mitochondria, efficient antioxidant and DNA repair systems, as... >> MORE

2007 new Scholar Award in aging

Aging is characterized by a progressive deterioration of tissues and organs that is in part caused by the accumulation of damaged proteins and organelles with age. Recent studies suggest that excess or defective organelles and cytoplasmic components are recycled through the autophagy-lysosome... >> MORE

2002 new Scholar Award in aging
A common feature of aging is the accumulation of abnormal or damaged proteins inside cells with a consequent negative effect in cell function. Any attempt to remove these abnormal proteins may help in the functional recovery of different organs affected in aged organisms. Damaged or abnormal... >> MORE
1999 new Scholar Award in aging

As we age, neurons in our brain tend to accumulate abnormal protein. The same process occurs in degenerative diseases of aging such as Alzheimer and Parkinson diseases, but at a much faster rate. Our research aims to identify the various ways that abnormal protein accumulation compromises the... >> MORE

1998 new Scholar Award in aging

Apoptosis is a genetically regulated form of cell death which is critical for the normal development and adult function of multicellular organisms. Inappropriate activation of apoptosis also contributes to the neuronal cell loss associated with acute brain injuries such as stroke, and in age-... >> MORE