Cellular senescence is a useful in vitro model for exploring molecular mechanisms underlying normal human aging. A popular hypothesis is that when the telomeres shorten to below a critical point, it acts as a mitotic clock dictating the permanent exit from the cell cycle. Besides telomere...

Oxidative stress contributes substantially to numerous human diseases and aging. Dietary restriction (DR), a dietary regimen that ameliorates various diseases and extends lifespan, reduces the steady state levels of oxidative stress and damage. DR has been postulated to reduce oxidative stress...

The long-term goal of my research program is to understand the molecular and genetic mechanisms governing the regulation of lifespan and age-related diseases including diabetes, sarcopenia, neurodegeneration, and neoplasia. The rate of aging across many species is influenced by common...

Apoptosis is a form of programmed cell death necessary for the deletion of damaged, defective or expired cells. Cells undergoing apoptosis must be removed swiftly in order to prevent leakage of potentially toxic and inflammatory contents from the expired cells into the surrounding tissue. A...

Increasing evidence points to a genetic basis for the regulation of the onset of senescence as well as the specific physiological manifestations of aging. Unbiased genetic screens using yeast, as well as invertebrates such as the fly or nematode, have been quite successful to uncover regulatory...

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...

The accumulation of somatic (non-heritable) DNA mutations over time is a hallmark and potential mechanism of aging. Current theory postulates that un-repaired, stochastic DNA damage results in random DNA mutations that accumulate over time within individual cells, and are passed on as these...

The tumor suppressor p53 protein has dual functions on longevity. First, p53 plays a crucial role in tumor suppression to prevent early death due to cancer. Second, p53 also regulates the aging process as demonstrated in mouse models. Constitutively increased p53 activity promotes aging and...

Manipulations of diet can extend the lifespan of organisms ranging from yeast to mice. Whether the mechanisms underlying these interventions are conserved from invertebrates to mammals is unknown. The fruit fly, Drosophila melanogaster, offers powerful tools for studying the relationship of...

Physiological aging is characterized by a complex set of cellular changes, including epigenetic alterations. Epigenetic mechanisms ensure that descendant cells inherit the identity of their predecessors, by marking the genome in a manner that persists through cell division. Importantly,...

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...

The total surface of the intestinal epithelium reaches 300m2 in humans, roughly the size of a tennis court. The intestines of vertebrate organisms are exposed daily to large amounts of antigens that in the great majority are innocuous, originating from the diet and from the resident commensal...

As we progress into old age, our brain changes. The prefrontal cortex, an area responsible for high-level cognitive functions such as attention, and its input for dopamine neurons that convey learning related signals, are particularly susceptible to age-related modifications. In this project we...

Some effects of aging have been attributed to a progressive decline in the ability of stem cells to maintain normal adult tissues or to repair injured tissues. Therefore, enhancement of natural tissue repair could in principle treat or prevent age-related illnesses. These efforts would be...

Aging is characterized by a progressive decline of tissue function associated with loss of regenerative potential. With age stem cell compartments are progressively less efficient in maintaining tissue homeostasis, and tissues undergo atrophy. These changes have been associated with critical...

The aging process is characterized by accumulation of age pigment, increased fat deposition, and increased susceptibility to aging-associated diseases. Age pigment is formed as a function of accumulated cell damage and breakdown of normal cellular components. Age pigment is increased in certain...

Fat metabolism undergoes fundamental changes during aging. Even when they maintain similar physical activities and diet choice, people commonly experience an unwanted increase in fat deposition starting at middle age. Less notably, the composition of fat storage is also different in later age....

Mitochondrial dysfunction is a pathological hallmark of aging-dependent human diseases such as cardiovascular disorders, cancer, stroke and neurodegenerative diseases including Parkinson

Caloric restriction is the only proven regimen to date that extends lifespan. It also delays the onset of age-related disorders, including diabetes, cancer, and neurodegenerative diseases. How caloric restriction regulates lifespan and health span is a fundamental question in aging research....

Most of the DNA in our cells exists as a stable double-stranded molecule that is packaged into a compact structure known as chromatin. This compact or 'closed' structure prevents the interaction of the DNA with specific factors. During certain normal cellular activities such as DNA replication...

Aging is accompanied by deterioration of brain functions. The discovery of neural stem cells and new neurons in the adulthood brings the hope of brain rejuvenation. However, the ability of neural stem cells to proliferate and to generate neurons decreases profoundly with the aging process. Yet,...