The decline of cognitive function is one of the greatest health threats for the aged population. It has been widely accepted that mainly loss of synaptic connections, rather than loss of neurons, is responsible for age-associated cognitive impairment. However the molecular mechanisms...

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...

There are many benefits to getting older including the wisdom that comes with greater life experiences. However, the ‘baggage’ that our bodies accumulate at the cellular level as we age can compromise our ability to enjoy those benefits. This lack of ‘cellular self-renewal’ is believed to be...

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...

The goal of our project is to investigate the impact of the metabolism of phosphoinositides on the neurological manifestations of aging. Phosphoinositides are low abundance membrane phospholipids that have key roles in signaling, membrane trafficking, and cytoskeletal dynamics in all cells....

A key element of cellular biology is that DNA is copied into mRNA which is then made into protein through a process called translation. The production of proteins through the process of translation provides the foundation for much of cellular functioning. Translation can occur in different...

Human aging incorporates multiple changes throughout the body such as slower metabolism and loss of muscle. Aging is also associated with a reduced aerobic capacity as a result of reduced lung function, poorer blood circulation, decreased cardiac output, and limited exercise capacity. These age-...

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...

The overall purpose of the work in our laboratory is to demonstrate that there is a hormonal regulation of organismal aging. This work is based on the observed effect of the bone-derived hormone osteocalcin in favoring glucose homeostasis, energy expenditure and male fertility. These three...

For adult stem cell transplantation, stem cells are harvested from fat, bone marrow, or other sites and are then transplanted back into injured or diseased organs. Stem cells from a patient can be transplanted back into the same patient, reducing chances of rejection. This approach holds...

The overall goal of this project will be to test our hypothesis that stimulating anabolic pathways in skeletal muscle may lead to extension of life span. Specifically, we will examine the effect of blocking the myostatin signaling pathway on longevity in mice. We discovered myostatin as a...

Muscle fatigue is one of the most fundamental physiological processes. Fatigue of skeletal muscle determines the outer limits of physical activity and explains, for example, why an elite athlete who can run 100 meters in under 10 seconds cannot run 1,000 meters in 100 seconds. Severe muscle...

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...

“You are only as old as your plumbing.” With that characteristically pithy remark, Sir William Osler summarized his view of the relationship between aging and diseases that affect the vascular system, the body’s plumbing. One hundred years later, vascular diseases remain a leading cause of death...

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...

The p53 protein is a prominent tumor suppressor, often referred to as the “guardian of the genome”. p53 is stabilized and activated in response to a variety of stress signals and, in turn, activates specific target genes through its function as a conventional transcription factor that binds to...

With “normal” aging, many individuals experience a profound loss of muscle strength. The changes in muscle structure that lead to muscle weakness are the basis of the degenerative disease known as sarcopenia, which has become a major affliction for millions of people worldwide. While many...

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...

The overall goal of our application is to initiate a novel series of studies that demonstrate a role for the hypothalamus in regulation of aging and age-related disease. Several studies suggest that hypothalamic mechanisms regulate aspects of aging in both invertebrates and vertebrates but their...

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...

Diseases of the Central Nervous System (CNS) - the brain, spinal cord and retina - typically cause permanent damage due to its poor regenerative power: unlike tissues such as the skin, it does not wound-repair efficiently. Hence the discovery that the CNS contains two small regions with stem...