Wednesday, September 23, 2009

One afternoon in NIA: on the variegated landscape in biology of aging

There exist a variety of ways for scientists to go about studying aging. Ever since the creation of the biology of aging as a field with the hope of addressing emergent problems associated with global population aging, this complex subject has triggered myriad scientific imaginations. Some hold that aging is a developmental stage, which manifests itself through breakdowns of various physiological architectures, thus understanding aging relies on studies in developmental biology. Others disagree, emphasizing the role of environmental damages and errors in protective machinery of organisms. For example, one research program studies the age-related dynamics between the processes of the damage and repair of DNA, molecules that carry the information of life. Yet others do not regard the mechanism of aging, whatever it is, is as important as the physiological programs that ensure individual life span. Centenarian genetics, and the molecular signaling triggered by caloric restriction, fall into the category of studying biological basis of life span and longevity, whose results often feed the drug development industry with potential schemes of making “Elixir”.

In some sense, even the most brilliant mind in biology can only grasp limited aspects of aging. When a group of curious blinds poke around a big elephant, however sensitive and discerning they are, what they learn largely depends on the particular location of their footholds. In the case of biogerontologists, the scientific footings are constrained by various theoretical predilections and experimental arrangements. But still, where does those diverse footholds come from?

The author visited the Intramural Research Program of National Institute on Aging (NIA) located in Baltimore for an afternoon this August, chatting with six researchers there. Those conversations were initially intended to help explore the landscape of aging research, and they turned out to shed light on the lineage of various takes of aging among biogerontologists. As a nascent branch of biology and biomedicine, the study of aging does not enjoy many researchers trained native in the field. Most of them came to focus on aging from the trajectory of their original studies, along with their former disciplinary leanings. Consequently, the approaches in aging are often the fruits of cross-fertilizations between the motive of studying aging and the methods from branches of biology and biomedicine.

David Schlessinger arranged the marriage between genomics and the study of age-related disease. Having worked for his PhD in Harvard in the wake of the discovery of the DNA “double helix” in the 1950s and thereafter a researcher in the Pasteur Institute on gene regulatory expression in bacteria, Schlessinger joked that he always ended up in the right place at the right time. His timely contribution also includes a 10-year direstorship of the Human Genome Center at Washington University. Witnessing the unfolding of human genome, Shlessinger regarded the technologies needed for genetic and genomic study on human aging became mature. Geneticists could now identify the different genetic sequences and expression patterns between phenotypically differed cohorts using chips and locate relevant loci on chromosomes through database at researchers’ fingertips. In 1997, he undertook the position of Chief of the Laboratory of Genetics in NIA. Working along the methods of genomics and population genetics, he constructed X chromosome map, discovering a number of disease genes, some of which related to human aging.

Sige Zou focuses his research on the change of life span in fruit flies and round worms brought by dietary restriction (DR) and deprivation. The research on dietary restriction is booming in the field of biology of aging, although many deemed the prolongation of life made by DR is not much more than a laboratory artifact. It combined the knowledge gained through decades of study in model organisms such as D. melanogaster and C. elegans, with molecular biology of nutrition signaling, and translational efforts. In such programs, not aging, but the mechanisms of life span and those of longer life span, are under investigation.

The researchers the author talked to also include Weidong Wang, who brought his experitise in biochemistry to the study of a progeric disease, Fanconi anemia, and Yie Liu, who transferred her molecular study in cancer cells, with considerations on DNA repair and telomere maintenance, into the study of cells at the intersection of senescence and malignancy.

Developed late relative to other subdisciplines of biology, the biology of aging became a topic that engaged a variety of existing methods from other branches and adapted them into its own utilization. The lack of consensus on the causes of aging, and the prioritization of research on various age-related diseases further expanded the purview of biology of aging, allowing researchers from many fields wield their disciplinary skills. The discrete but multiple scientific programs welcome alternatives in researching aging, which made complementary studies possible. However, also due to this status quo, the limited resources of aging research are dispersed into scattered efforts, which may inhibit the productivity and efficiency of the truly important approaches. In addition, how to connect the dots derived from various approaches into a coherent understanding of aging is an issue yet to resolve. A tentative question is whether it is possible to combine various approaches and melt them down to a grand methodology of aging research in biology, without compromising the current richness and diversity. Before those questions are answered, the biology of aging will continue to display its exceptional chirography in theoretical diversity and experimental multiplicity on its scientific frontier.

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