The Future of Human Healthspan Demography, Evolution, Medicine, and Bioengineering: Task Group Summaries (2008) / Chapter Skim
Currently Skimming:
Cellular and Molecular Mechanisms of Biological Aging: The Roles of Nature, Nurture, and Chance in the Maintenance of Human Healthspan
Cellular and Molecular Mechanisms of Biological Aging: The Roles of Nature, Nurture, and Chance in the Maintenance of Human Healthspan
Pages 73-92
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 73... ...
The major factor determining variations in healthspan and lifespan between species is genetic inheritance. Broader aspects of cellular and molecular mechanisms of biological aging will also be considered, given their importance for understanding the cellular and molecular basis of successful aging.
|
From page 74... ...
They could be related to the intrinsic instability of the transgene, making it important to repeat such experiments utilizing endogenous genes as reporters of the response to heat shock and other stressors. It could be due to epigenetic drifts in gene expression, perhaps involving random changes in gene promoters or in the state of chemical modifications to histone proteins that coat chromosomes.
|
From page 75... ...
Initial Challenges to Consider • What experiments might be designed in model organisms to probe the role of variations of endogenous gene expression at birth in the determinations of the remarkable stochastic variations in lifespan among genetically identical organisms? • Which subset of endogenous genetic loci are major contributors to such stochastic variation?
|
From page 76... ...
determine patterns of gene expression and patterns of aging in human subjects? • Do genetic interventions that increase mean but not maximum lifespan, and appear to rectangularize the lifespan curve, act by reducing random events?
|
From page 77... ...
Please be sure to explore the other write-up, which immediately follows this one. TASK GROUP MEMBERS -- Group A • Diddahally Govindaraju, Boston University • Stephanie Lederman, American Federation for Aging Research • Kyongbum Lee, Tufts University • Richard Mayeux, Columbia University • Saira Mian, Lawrence Berkeley National Laboratory • Chris Schaffer, Cornell University • Nicholas Schork, Scripps Genomic Medicine, Scripps Health • Rob Stephenson, Emory University • David Stopak, The National Academies • Richard Suzman, National Institute on Aging • Woodring Wright, University of Texas Southwestern Medical Center • Alissa Poh, University of California, Santa Cruz
|
From page 78... ...
This group was hence charged with examining stochastic variation's potential influence on human lifespan. Very early in the discussion, however, it became clear that many group members were uncertain that investigations in this area should be a priority, and spent much of the first day debating its importance.
|
From page 79... ...
" Genetic screens involving model organisms were suggested. The group acknowledged these to be incredibly valuable, although some members were skeptical about the potential for human genetic screens via genomewide association studies.
|
From page 80... ...
Still, the group felt that it would shed light on the potential role of stochastic factors in aging. Fine Tuning the Experimental Model Much of the second day was spent refining this proposed experiment.
|
From page 81... ...
Among the examples of mechanisms these screens miss are the role of stem cells in aging, the importance of neoteny in the evolution of human lifespan, and most significantly, the key issue this group was asked to explore, with longevity in mind: stochastic variation in gene expression. The Game Plan in a Nutshell As mentioned earlier, changes in swimming behavior can be detected in C
|
From page 82... ...
And when you've arrived there, it doesn't really matter how you were pushed; you got to the bottom of the hill, to a common state associated with senescence." If this hypothesis is true, a potential secondary analysis would identify individual genes and pathways implicated in the fingerprint of senescence. Figure 2 Hypothesis -- "Many roads to Rome."
|
From page 83... ...
In the second hypothesis, which Figure 3 illustrates, random variation in gene expression within or between specific cells drives lifespan differences. These cells become dysregulated, ultimately losing their ability to function as part of their tissue of residence.
|
From page 84... ...
So there's still an important role for individual entrepreneurship to tackle isolated problems and find new handles to push, in terms of discovering new aging mechanisms." TASK GROUP MEMBERS -- Group B • Suresh Arya, National Cancer Institute • Christine Grant, North Carolina State University • Linda Miller, Nature • Richard Miller, University of Michigan • Santa Jeremy Ono, Emory University • Chris Patil, Lawrence Berkeley National Laboratory • Jerry Shay, University of Texas Southwestern Medical Center • Eric Topol, Scripps Research Institute • Michael Torry, Steadman-Hawkins Research Foundation • Heinz-Ulrich G Weier, Lawrence Berkeley National Laboratory • Iris Tse, Boston University TASK GROUP SUMMARY -- Group B By Iris Tse, Graduate Writing Student, Boston University I have cataracts, lose uphill races, get really sick when I catch the flu, girls no longer whistle when I pass by, my joints ache, and if you looked closely you'd see preclinical signs of the cancer that will kill me.
|
From page 85... ...
The stochastic model proposed that factors extending average lifespan, but not the maximum lifespan, played a major role in extending healthspan. The group felt that the basis of this view was somewhat biased and would exclude many healthspan factors that also extend maximum lifespan.
|
From page 86... ...
If we can understand why humans get cataracts at 60 years old and why mice get cataracts at 2 years old, we might be able to delay the onset of these symptoms, prolong healthspan, and understand aging a little better. Miller insisted that it will be useful to find themes, or common families, of underlying cellular or molecular factors that time aging sequentially.
|
From page 87... ...
Otherwise, you'd get mired over things like the trial and error of a new experimental design," said Chris Patil, a postdoctoral scholar of life sciences from Lawrence Berkeley National Laboratory. The next step will be to select the proper animal models for interspecies comparison.
|
From page 88... ...
"This umbrella approach is a better way to probe the age-diseases nexus by exploiting the power of comparison." TASK GROUP MEMBERS -- Group C • Craig Atwood, University of Wisconsin-Madison • Miles Axton, Nature Genetics • Rita Effros, University of California, Los Angeles • Nan Jokerst, Duke University • Jay B Labov, National Academy of Sciences • Valter Longo, University of California, Los Angeles • Joao Magalhaes, Harvard University • Ken Turteltaub, Lawrence Livermore National Laboratory • C atherine Wolkow, National Institute on Aging, Intramural Research Program, National Institutes of Health • Natalia Mackenzie, Boston University TASK GROUP SUMMARY -- Group C By Natalia Mackenzie, Graduate Writing Student, Boston University For many people, aging is taken for granted.
|
From page 89... ...
, carcinogens, replication errors, among others. Another crucial environmental factor that affects aging is socioeconomic status (SES)
|
From page 90... ...
During the second day, the group focused on building a tangible proposal that would represent their ideas and conclusions. They first decided that their working hypothesis would be that aging results from increasing cellular damage that compromises communication pathways, leading to impaired cellular functioning and organ failure.
|
From page 91... ...
The idea is to use these new tools to intervene in the aging process by repairing, reprogramming, removing, or replacing damaged biological components of cells that contribute to the deterioration of the human body. Specifically, they proposed to focus on organ systems that are mostly affected in aging like vasculature, the nervous system, musculoskeletal, immune, vision, and hearing.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.