Aging and Longevity Research

The Biology of Aging and Senescence

John D. Furber

Master of Science, Biological Sciences, University of California, Irvine.
Bachelor of Arts, Physics and Mathematics, University of California, Santa Cruz.

[John D. Furber home page]

Senescence is the biological process of age-related deterioration in function.

The development of consciousness and maturity takes time...
It is grimly ironic that as adults mature and begin to develop the wisdom
to live their lives well,
the processes of senescence begin to weaken the body and mind,
halting maturation and eventually causing death.

-J.D. Furber

The study of human senescence has been fraught with controversy, conflicting theories, and puzzling data. Indeed, "pure" senescence is often difficult to distinguish from diseases of old age. Medical science has cataloged many signs of senescence. It manifests as dozens of changes in cells, tissues, and organs during aging. Human life is supported by a complex network of biochemical substances and reactions which affect the physical state and vitality of the body and mind. Senescent changes can be seen in the rate and outcome of many of these reactions. However, many of these changes are secondary effects of senescence, rather than primary causes. A summary of secondary effects in human aging can be found in the Dossier on Ageing prepared by the Health on the Net Foundation

Disposable Soma Theory for the Evolution of Senescence:

It is noteworthy that the germ line of egg and sperm has been maintained alive and safe from senescence and oxidative decay for over a billion years. Our life is part of an unbroken chain of life, extending back in time to our earliest ancestors.

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Mechanisms of Senescence:

A variety of hypotheses have proposed mechanisms of senescence. It appears that several distinct mechanisms of senescence are acting in parallel and interacting with each other:

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Ideas for Developing Therapies:

Human intellect has evolved to the point of developing technology
to consciously direct the heretofore randomly-evolved cellular processes
and finally allow realization of the age-old dreams of rejuvenation.

-J.D. Furber

Any factors which protect or fail to protect us from senescence and death must either be produced by our cells from instructions coded in their genes, or else brought in from outside, like nutrients or drugs.

Therapeutic interventions which might enhance the body's maintenance and repair systems may include:

  • Inhibiting or reversing the glycation and crosslinking of extracellular proteins;
  • Inhibiting or removing the accumulation of lipofuscin/ceroid and other crosslinked aggregates in nondividing cells;
  • Deactivating or slowing the production of highly reactive chemicals (ROS or free radicals);
  • Chelating excess iron, especially in neurons;
  • Repairing or replacing damaged DNA, proteins, membranes, and mitochondria;
  • Selectively blocking that portion of the insulin receptor signaling pathway which may cause senescence effects;
  • Maintaining the telomeres at the ends of the chromosomes, or else treating the effects of shortened teleomeres;
  • Injecting or grafting replacement cells or tissues to provide the functions which were formerly provided by cells which became senescent or damaged. (Sometimes called "transplantation".) Some techniques under development use multipotent stem cells.
  • Injecting hormones to bring blood concentrations to levels found naturally in young people.

Tutorials and Information Sites

  • The SAGE KE - Science of Aging Knowledge Environment is maintained by the AAAS. sageke.sciencemag.org/
  • SAGE Crossroads is an online forum for emerging issues of human aging. Launched in March 2003 by the AAAS and the Alliance for Aging Research, SAGE Crossroads explores the impact of science and technology on aging. www.sagecrossroads.com
  • Aubrey de Grey and some dedicated volunteers run the SENS website. SENS is an acronym for Strategies for Engineered Negligible Senescence. www.sens.org
  • The InfoAging.org web site is maintained by AFAR, the American Federation for Aging Research www.infoaging.org/.
  • The Novartis Foundation for Gerontology has the Health and Age website with a Primer on "Ageing & Its Implications". www.healthandage.com/html/res/primer/index.htm
  • The Stanford University Symposium on Aging, March 13, 2001 can be viewed in RealPlayer video at www.med.stanford.edu/lane/ifo/cme/cme-aging.html
  • Scientific and Educational Website on Human Longevity is maintained by Dr. Leonid Gavrilov and Dr. Natalia Gavrilova at the University of Chicago, Center on Aging longevity-science.org

Discussion Groups and News Groups

Research Institutes, Foundations, Organizations

  • The National Institute on Aging (NIA) of the U.S. Government National Institutes of Health funds biomedical research on senescence and lifespan. Their web site contains information on the research topics of greatest interest to NIA, as well as instructions on applying for grants. http://www.nia.nih.gov/
  • The Ellison Medical Foundation (EMF) has been established by a gift of $100 million from Mr. Lawrence J. Ellison, Chairman of Oracle Corporation, "to support biomedical research on aging, including basic biology, epidemiology, and clinical investigation." They are currently providing support to about two dozen researchers at various universities and institutes in the United States. Recent recipients include:
    • Seymour Benzer, California Institute of Technology
    • Judith Campisi, Lawrence Berkelely National Laboratory
    • Anna Maria Cuervo, Albert Einstein College of Medicine
    • James W. Curtsinger, University of Minnesota
    • Thomas E. Johnson, University of Colorado
    • Cynthia J. Kenyon, University of California, San Francisco
    • Michael R. Rose, University of California, Irvine
    • Gary Ruvkun, Massachusetts General Hospital
    • Rudy Tanzi, Massachusetts General Hospital
    The Ellison Medical Foundation co-sponsors an annual Colloquium on Aging each August at the Woods Hole Marine Biology Laboratory. Admission is free to the public.
  • The American Aging Association, Inc. The American Aging Association was founded in 1970 as a non-profit, tax-exempt national organization of lay and scientific members dedicated to promoting biomedical aging studies directed toward slowing down the aging processes. It holds an annual scientific symposium and publishes the Journal of the American Aging Association.
  • The International Association of Biomedical Gerontology (IABG) meets every 2 years, in a different country each time. The next meeting is the 12th Congress on the Greek island of Spetses, 20 - 24 May 2007. http://www.eie.gr/nhrf/institutes/ibrb/spetses-2007/aboutIABG.html
  • The American Federation for Aging Research (AFAR) supports "biomedical research that promotes healthier aging" and furthers "understanding of the aging process and its associated diseases and disorders." AFAR also produces the InfoAging.org web site.
  • The Andrus Gerontology Center and Leonard Davis School of Gerontology of the University of Southern California.
  • The Brookdale Foundation National Leadership in Aging Program offers 2-year Fellowships to support the development of the next generation of leaders in Geriatrics and Gerontology.
  • The Buck Institute for Age Research in Novato, California is an independent, nonprofit research institute dedicated to studying the nature of the aging process and what factors trigger age-associated disease. They do not give grants.
  • The Centenarian Species and Rockfish Project is studying the biological basis for the extreme longevity of certain species which live for more than 100 years, and yet do not show signs of senescence.
  • The Gerontological Society of America (GSA) holds an annual scientific meeting and publishes the Journal of Gernontology: Medical Sciences and the Journal of Gernontology: Biological Sciences.
  • The Alzheimer's Association is the largest national voluntary health organization supporting Alzheimer research and care. http://www.alz.org/
  • The Glenn Foundation for Medical Research "was founded in 1965 by Paul F. Glenn. Its purpose is to extend the healthy productive years of life through research on the mechanisms of biological aging. Grant applications are not accepted."
  • The International Longevity Center - USA is an institute for research and policy on aging.
  • The LA Gerontology Research Group is an educational not-for-profit organization which holds monthly educational meetings in the Los Angeles area.
  • The Kronos Group http://www.kronosscience.com includes an optimum health clinic, medical laboratory, and physician credentialing programs, as well as a research institute, the Kronos Longevity Research Institute. http://kronosinstitute.org
  • The Life Extension Foundation publishes Life Extension magazine, and sponsors a research program in Aging and Longevity. They also sell vitamins, antioxidants, and books.
  • The Linus Pauling Institute of Oregon State University was co-founded in 1973 by Linus Pauling. The institute's mission includes "to determine the function and role of micronutrients, vitamins and phytochemicals in promoting optimum health and preventing and treating disease; to determine the role of oxidative and nitrative stress and antioxidants in human health and disease." They have an informative website at http://lpi.orst.edu
  • The New England Centenarian Study http://www.bumc.bu.edu/Departments/HomeMain.asp?DepartmentID=361
  • The aim of the Novartis Foundation for Gerontological Research (formerly, the Sandoz Foundation for Gerontological Research) "is to promote science concerned with the problems of aging or the problems of the aging individual. Areas of interest are in the fields of biology, pharmacology, immunology, general geriatrics, geriatric psychiatry (behavioral aspects), and geriatric internal medicine. It is the intent of the Foundation to promote mainly innovative research projects using novel approaches which may lead to new findings in the area concerned. The Foundation alsoendeavors to sponsor specifically the work of researchers new to the field. A maximum of $35,000 will be awarded for each grant approved." Phone: (201) 503-8544. See also the Novartis Bulletin:
  • O2SA - the Oxidative Stress and Aging Association is "an organization of scientists and physicians dedicated to advancing the field of oxidative stress and aging in diagnostics and therapeutics worldwide." Their last international symposium was held in April 2001 on the island of Maui. It attracted very high quality scientists who shared their latest research findings. The o2sa web site has listings of articles, conferences, companies, and organizations. http://www.o2sa.org
  • OCC - the Oxygen Club of California holds an excellent scientific meeting in Santa Barbara every March. http://www.oxyclubcalifornia.org
  • Research into Ageing is a registered charity in the UK "dedicated to understanding and challenging the diseases and disabilities which become more common later in life." http://www.ageing.org/
  • The Symposium on Organisms with Slow Aging (SOSA) was held 22-23 September 2000 and 17-18 January 2003 at the University of Southern Californa Andrus Gerontology Center.
  • University of California, Davis Center for Aging and Health http://www.ucdmc.ucdavis.edu/research/health_system_research/Aging.htm
  • The University of Wisconsin - Madison Institute on Aging.
  • The Wolfson Centre for Research on Age Related Diseases at King's College London http://www.kcl.ac.uk/depsta/biomedical/CARD/CARD.htm
  • A4M - American Academy of Anti-Aging Medicine is a nonprofit organization of physicians and scientists that is dedicated to the advancement of therapeutics related to the science of longevity medicine.
  • Bruce Ames, Professor of Biochemistry & Molecular Biology, University of California, Berkeley. The Ames lab is researching "mechanisms of aging, with an aim of delaying the degenerative diseases of aging."
    • Mitochondrial decay in aging.
    • Oxidants and antioxidants in DNA damage.
    • Micronutrient deficiencies and DNA damage.
    • Chronic inflammation and Cancer.

Companies

  • Cortex Pharmaceuticals http://www.cortexpharm.com/ is developing memory-enhancing drugs which may help with Alzheimer's and senility.
  • Geron Corporation is a biopharmaceutical company studying telomerase, the genomics of aging, and cellular aging and immortalization. It is "exclusively focused on discovering, developing and commercializing therapeutic and diagnostic products to treat cancer and other age-related diseases."
  • Human Genome Sciences is using the techniques of functional genomics and proteomics to discover genes involved in signaling, to develop therapies which help the body to repair, rebuild, and restore those organs and cells damaged by disease, trauma, or age. They call this concept Regenerative Medicine.
  • Legendary Pharmaceuticals has been established to develop therapeutic drugs and gene therapies to slow the aging processes and repair the damage which occurs during aging.

Video Documentaries

Never Say Die is a Scientific American Frontiers documentary which first aired on January 25, 2000 on PBS. It features interviews with:
  • Roy Walford, UCLA
  • Calvin Harley, Geron Corporation
  • Cynthia Kenyon, UCSF
  • Gordana Vunjak Novakovic, MIT
  • Marilyn Albert, Massachusetts General Hospital
Stealing Time: The New Science of Aging is a three-hour PBS documentary released in June 1999. The videotapes are available from PBS Home Video at 1-800-PLAY-PBS. (The companion book is not illustrated, is not a transcript, and is not as well researched as the video itself.)

Part I, "The Quest for Immortality," features interviews with:

  • Tom Perls, Harvard Medical School,
  • Whit Gibbons, University of Georgia,
  • Steve Austad, University of Idaho, University of Washington School of Medicine,
  • Jared Diamond, UCLA School of Medicine,
  • Michael Rose, University of California, Irvine,
  • Tom Johnson, University of Colorado.

Part II, "Turning Back the Clock," features:
  • Roy Walford, UCLA,
  • Lisa Walford, yoga teacher,
  • Richard Weindruch, University of Wisconsin, Madison,
  • Anthony Cerami, The Kenneth S. Warren Laboratories,
  • Raj Sohal, Southern Methodist University,
  • Miriam E. Nelson, Tufts University School of Nutrition Science and Policy ,
  • Mitchell Harman, National Institute on Aging,
  • Judith Campisi, Lawrence Berkeley National Laboratory.
  • Marc Blackman, National Institute on Aging
  • Joseph Kemnitz, University of Wisconsin, Madison
  • Peter Ulrich, The Kenneth S. Warren Laboratories

Part III, "Mastering the Mind," examines how the mind and brain change with age. It features research by:
  • Marilyn Albert, Harvard Medical Center,
  • Paul Coleman, University of Rochester Medical Center,
  • Carl Cotman, Institute for Brain Aging and Dementia, University of California at Irvine,
  • Marian Diamond, University of California at Berkeley,
  • William T. Greenough, Beckman Institute for Advanced Science and Technology,
  • Ernst Mayr, biologist,
  • Timothy Salthouse, Georgia Institute of Technology,
  • Robert Sapolsky, Stanford University,
  • K. Werner Schaie and Sherry Willis, Seattle Longitudinal Study and Penn State University,
  • Arnold Scheibel, UCLA,
  • Barbara Sherwin, McGill University.

Articles

  • Medline PubMed provides access to the Medline database of Biomedical journal articles maintained by the U.S. National Library of Medicine. http://www.ncbi.nlm.nih.gov/pubmed
  • Journal of Anti-aging Medicine. (This journal has since been renamed, "Rejuvenation Research.") Special issue on "Mitochondria and Free Radicals." Vol 2 (3) Fall 1999, (Mary Ann Liebert, Inc.)
  • Kenneth B. Beckman and Bruce N. Ames. "The Free Radical Theory of Aging Matures," Physiological Review, Vol 78 (2) April 1998. (Review article).
  • A. Terman and U.T. Brunk. "Lipofuscin: Mechanisms of formation and increase with age," APMIS. Vol 106 (2): 265-276 (Feb 1998) (Review article).
  • Cerami, Vlassara, Brownlee. "Glucose and Aging", Scientific American. 256: 90 - 96 (1987).
  • UCLA Roundtable: Critical Future Milestones in Aging Research February 19-20, 1999.
  • YJ Lin, L Seroude, S Benzer. Extended Life-Span and Stress Resistance in the Drosophila Mutant methuselah. Science. 282, 30 Oct 1998, pp. 943-946.
  • Douglas C. Wallace. "Mitochondrial Diseases in Man and Mouse," Science. 5 March 1999, pp. 1482-1488.
  • Douglas C. Wallace. "Mitochondrial DNA in Aging and Disease," Scientific American. August 1997, pp. 40-47.

Books

  • Steven N. Austad. Why We Age: What Science Is Discovering about the Body's Journey through Life. (John Wiley & Sons, 1997).
  • Aubrey de Grey. The Mitochondrial Free Radical Theory of Aging. (R G Landes Co, 1999).
  • Caleb E. Finch. Longevity, Senescence, and the Genome. (University of Chicago Press, 1990).
  • Harvey Lodish, David Baltimore, et.al. Molecular Cell Biology. (W.H. Freeman & Co., Fourth Ed., 2000).
  • Lubert Stryer. Biochemistry (W. H. Freeman & Co., Fourth Ed., 1995) p. 537.
  • Roy L. Walford. Maximum Lifespan. (WW Norton & Co., 1983).

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Contact information:

John D. Furber
E-mail: johnfurber (at) gmail com
Telephone: 1-352-271-8711
Gainesville, Florida.
[John D. Furber home page]
© 2000 - 2011 by John D. Furber. All rights Reserved.