Professor Alea A. Mills

The EurekAlert Gene loss accelerates aging said

Researchers have discovered that the loss of a gene called p63 accelerates aging in mice. Similar versions of the gene are present in many organisms, including humans. Therefore, the p63 gene is likely to play a fundamental biological role in aging-related processes.
 
“To study how the p63 gene works, we devised a system for eliminating it from adult mouse tissues. What struck us right away was that these p63 deficient mice were aging prematurely,” says Alea Mills of Cold Spring Harbor laboratory, who led the research.
 
“Aging and cancer are two sides of the same coin. In one case, cells stop dividing and in the other, they can’t stop dividing. We suspect that having the right amount of the p63 protein in the right cells at the right time creates a balance that enables organisms to live relatively cancer-free for a reasonably long time,” says Mills, who adds that this is the first time the p63 gene has been implicated in aging.

Alea A. Mills, Ph.D. is Associate Professor at Cold Spring Creek Laboratory. Mammalian functional genomics is the major thrust of her laboratory. She explores gene function in vivo using the mouse as a model system. Her goal is to develop and characterize novel models that mimic human cancers and developmental syndromes in order to investigate the genetic and molecular basis of pathogenesis.
 
Chromosome Engineering
 
Genomic analyses have revealed that human chromosome 1p36 is frequently deleted in neural, epithelial, and hematopoietic malignancies, indicating that this region harbors a tumor suppressor. However, this gene has remained elusive for three decades. She took a functional approach to identify a 1p36 tumor suppressor. Using chromosome engineering — Cre/loxP based system — she created mice with gains and losses of regions of the mouse genome that corresponds to human 1p36. This enabled her to identify a potent tumor suppressive interval. Loss of this region predisposes to cancer, whereas gain of this region results in excessive tumor suppression. She next identified Chd5 as the tumor suppressor within the region, and determined that the encoded chromatin remodeling protein Chd5 regulates a tumor suppressive network including p19/p53– and p16/Rb-mediated pathways. The epigenetic role of Chd5 in development, cancer, and stem cell maintenance is currently being investigated.
 
The p63 Gene
 
Using a variety of p63 mouse models, she determined that deficiency of the p53-related protein p63 causes developmental defects, protects from tumorigenesis, triggers cellular senescence, and leads to accelerated aging in vivo. These findings indicate that cellular senescence provides tumor suppression at the expense of compromising tissue homeostasis. She is currently investigating how p63 regulates senescence and how this impacts cancer and aging.
 
Alea authored p53: link to the past, bridge to the future and Changing colors in mice: an inducible system that delivers, and coauthored Dicer is essential for mouse development, p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors, Assembly of the QM protein onto the 60S ribosomal subunit occurs in the cytoplasm, Two new balancer chromosomes on mouse chromosome 4 to facilitate functional annotation of human chromosome 1p, Extreme evolutionary conservation of QM, a novel c-Jun associated transcription factor, and p63 deficiency activates a program of cellular senescence and leads to accelerated aging.
 
Alea earned her Ph.D. in Microbiology & Molecular Genetics at the University of California, Irvine, in 1997.