Dr. Jan Vijg
Principal Investigator, Vijg Lab
Buck Institute for Age Research
(The following is the summary of a presentation given by Dr. Vijg during a CREA meeting on May 9th, 2007)
Current trends of research in aging and longevity
The science of aging has long been dominated by either:
- highly descriptive research on senescent degeneration and death, or
- bold speculation about its origins and causes
However, with the discovery in the 1980s that single gene mutations could dramatically extend life span of the nematode worm, aging began to take its place as a problem that could be addressed in ways very similar to differentiation, development and disease. The field had now become a worthy object of study for highly reputed, well-funded scientists. At this point in time, there are hundreds of mutant genes in a variety of organisms, from yeast and fruit flies to mice, which significantly increase longevity through their effects on endocrine signaling, stress responses, and metabolism. Some of these gene effects intersect with caloric restriction, limiting calories without malnutrition, which is since long known to increase life span in multiple species. These dramatic developments have not left the scientific or lay community undisturbed. Indeed, in stark contrast with the past, there is now almost no issue of Nature or Science without at least one paper on an aging-related issue. The same is true for the various science sections of our better newspapers. Research on aging has been catapulted to the forefront of science rather than remaining a backwater. This development has come in parallel with an enormously increased capacity of the biomedical research community to handle complex biological problems in the laboratory. Together, these developments bode well for the science of aging, which has already led to substantial optimism with respect to the unraveling of its secrets.
However, there are at least three areas of potential concern.
First, with the discovery that single gene mutations could affect longevity and thereby an entire orchestra of physiological changes the debate whether aging is caused by a genetic program has come back with a vengeance. Indeed, while highly persuasive arguments, by eminent evolutionary biologists, with ample experimental support, should by now have convinced the scientific community that aging is merely a by-product of evolution and can never be a selectable trait, the demonstrated genetic manipulations of life span evidently provide new fuel to the old deterministic concepts of aging. It is important to realize that this renewed attention to old concepts is not supported by the data. Indeed, it is not aging that is programmed but the survival mechanisms, which are fluid and can be upregulated by dampening pathways of growth and reproduction.
Second, the strong focus on life span and its determinants have distracted us from the key problems associated with aging itself. While we know so much about the genetic factors determining life span of nematodes and flies we know very little about the causes of their demise. A renewed attention to the actual pathophysiology of aging across multiple model organisms seems opportune.
Finally, our success in increasing life span in model organisms in the laboratory through genetic or nutritional intervention together with the sheer infinite possibilities of the enew geneticsf with so many genomes deciphered and so many new opportunities for comprehensive molecular analyses and manipulation, has now led some to speculate that aging can surely be cured and that immortality is just around the corner. While pharmaceuticals that mimic nutritional and genetic longevity effects in humans are now under development, as are new approaches to remove macromolecular crosslinks and protein aggregates, it is premature to predict that increasingly sophisticated interventions over the next decades may negate most if not all the adverse effects associated with aging. Indeed, there is evidence that aging also involves a stochastic loss of cellular integrity leading to a gradual drift from concerted cellular activities towards more random behaviors. This drift might result in organ and tissue dysfunction that would not lend itself to straightforward pharmacological intervention. Moreover, the gains in longevity achieved by genetic and pharmacological interventions appear to decline with organismal complexity, suggesting that the life span of complex organisms is less plastic than that of simpler organisms. And then there is the cancer problem, which poses challenges to longevity that are distinct from age-related degenerative processes.
While there is no scientific reason for not striving to cure aging -- similar to what we profess to do for cancer and other complex diseases -- our current understanding of aging argues against the validity of predicting the possibility to significantly delay or reverse the aging process. Instead, we need to use the current momentum to intensify research aimed at in depth identification of basic mechanisms of aging, and major causes of human aging and age-related disease.
Link here for Dr. Vijg's page on the Buck Institute for Age Research website.