| Human cell types can be broadly
divided into cells that continue to divide over their life span and
those that do not. Tissues in the human body that undergo
continuous renewal, such as epithelia, depend on cells that continue to
divide (i.e., stem cells and amplifying cells). Other tissues,
such as most nervous tissue, contain cells that do not divide, but
remain functional over many years or decades (e.g., motor
neurons). Aging in both types of cells involves characteristic
changes due to loss of function over time. Cells that divide
undergo replicative aging,
which limits how many times they can divide. Cells that do not
divide undergo chronological aging,
which limits how long they remain viable and functional. The goal
of our studies is to identify and characterize processes that cause
replicative and chronological aging of cells. |
| Our studies use the budding (or
baker's) yeast Saccharomyces
cerevisiae as a model eukaryotic cell type. We use this
yeast
as an
experimental
system because of the ease of using various approaches in biochemistry,
cell biology, genetics, and molecular biology. Studies in yeast
are relevant
to human cells because many of the fundamental biological mechanisms of
aging are the same. Our goal is
to pursue an understanding of mechanisms
that regulate replicative life span in yeast cells and extend these
studies to other eukaryotic cell types, such as human cells.
Insights regarding aging processes in yeast should improve our
understanding of general
mechanisms
that regulate aging in eukaryotic cells, including human cells. |
| Replicative
Aging Yeast divide asymmetrically. A larger "mother" cell gives rise to a smaller "daughter" cell through a budding process (rather than cell fission). For most strains of yeast, mother cells typically divide less than 40 times (i.e., mother cells typically give rise to fewer than 40 daughter cells). Thus, replicative aging limits the number of daughter cells formed by a mother cell. Chronological Aging Chronological aging is the process by which non-dividing cells lose viability. In yeast, chronological aging takes place during a non-dividing state known as stationary phase. Stationary phase is a “quiescent” state in which cells exhibit a specific set of phenotypic characteristics, such as a reinforced cell wall, resistance to environmental stress, and accumulation of storage carbohydrates. Importantly, yeast cells in stationary phase are metabolically active, derive energy from aerobic respiration, and remain responsive to environmental signals. Thus, stationary phase is similar to the G0 phase in non-dividing cells that age chronologically in human tissues. Single gene mutations have been identified that affect the replicative and chronological life span of yeast cells. This indicates that life span is regulated. One of these genes, SIR2, regulates the life span of yeast as well as other organisms, such as worms and flies. One of the goals of our research is to identify genes that are important for regulating life span. By identifying and studying such genes, we hope to learn more about the mechanisms and pathways that influence the aging process. |