barzali

Institute for Aging Research

Molecular Genetics of Aging

With the recruitment of Dr. Jan Vijg as Chair of the Department of Genetics, a new focus of aging studies has been untaken in the area of molecular genetics. There is currently a focus on exploration of the basic mechanisms of aging in mouse models55-58. Furthermore, since ‘aging’ is now a major focal point in the Department of Genetics, faculty working with invertebrates and previously less interested in aging, have now begun to make inroads in this field, sometimes in unexpected and surprising ways. For example, Dr. Hannes Buelow, who studies heparan sulfate (HS) proteoglycans in the nematode59, recently discovered an interesting ortholog of a gene involved in HS sugar metabolism in the worm from among the set of association signals in Dr. Nir Barzilai’s whole genome association study of human centenarians. Dr. John Greally, who participates in the ENCODE project, became interested in DNA methylation in aging and has closely collaborated with Dr. Barzilai during the last year.

A host of questions is now being explored in the realm of molecular genetics, varying fromDNA damage and repair, telomeres60 to the functional genomics of unknown SNPs conferring extreme human longevity (Helfand, Sedivy, Tatar, Gorbunova, Collins). As described in the longevity program project (Barzilai, Suh, Atzmon, Lipton, Bergman), substantial advances have been made using high-throughput genetic modalities available in the Department of Genetics. Initial data on animal and humans shows changes in methylation with aging that are tissue-specific (Greally, Atzmon), and extend to animal and human models who develop age-related disease after intrauterine growth retardation (Einstein), and in brains of both sick and healthy elderly subjects (Zukin). 

  1. Holcomb, V. B., Rodier, F., Choi, Y., Busuttil, R. A., Vogel, H., Vijg, J. et al.Ku80 deletion suppresses spontaneous tumors and induces a p53-mediatedDNA damage response.Cancer Res68, 22:9497-9502, doi:68/22/9497 [pii]10.1158/0008-5472.CAN-08-2085 (2008).
  2. Park, J. Y., Cho, M. O., Leonard, S., Calder, B., Mian, I. S., Kim, W. H. et al. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging Xpd mice.PLoSONE3, 6:e2346, doi:10.1371/journal.pone.0002346 [doi] (2008).
  3. Melis, J. P., Wijnhoven, S. W., Beems, R. B., Roodbergen, M., van den Berg, J., Moon, H. et al.Mouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes.Cancer Res68, 5:1347-1353, doi:68/5/1347 [pii]10.1158/0008-5472.CAN-07-6067 (2008).