In part 2, we looked at oxidation and glycation as key agents in aging
and their relation to caloric restriction as a longevity-promoting
strategy.
In part 2, we looked at oxidation and glycation as key agents in aging and their relation to caloric restriction as a longevity-promoting strategy. In part 3, we continue our exploration of aging and longevity with a look at the genetic basis of how we age, health span versus life span and what early chiropractic philosophy has to say about notions of homeostasis and health maintenance.
GOLDEN GENES
Florence Green died on Saturday, February 4, 2012 – two weeks before her 111th birthday. She was the world’s last known veteran of the First World War. One of humanity’s exceptional survivors, her life spanned almost the entire last century and had a solid foothold in the 21st. When asked what it was like to be 110, she said “It’s not much different from being 109.”1
Bishop Otis Clark, the world’s most enduring travelling evangelist, turned 109 in February this year. Born in 1903, he served as a butler to Joan Crawford and waited on such notables as Charlie Chaplin and Clark Gable. He turned to God while in prison for bootlegging during Prohibition and has now been preaching for over 60 years. Referencing his faith during a recent visit to Toronto, Bishop Clark declared that his ability to persist stems from being “…on the winning side!”
Though Ms. Green’s and Bishop Clark’s longevity was extraordinary, Jeanne Calment of Arles, France, did even better. Mme. Calment lived to the age of 122 years, five months and 14 days. Born in 1875, she was 14 when the Eiffel Tower was completed and once sold painting supplies to Vincent Van Gogh who she described as “dirty, badly dressed and disagreeable.”2 Still vigorous in her later years, she took up fencing at age 85 and continued to ride a bicycle at 100. Mme. Calment lived longer than anyone in reliably documented history – she lived so long that she, herself, became part of history.
We now know that the practical limit of human life span is about 120 years. We know because Jeanne Calment did it. Her remarkable longevity currently benchmarks the gold standard for maximum human life span — the greatest age reached by any member of a species.
BUT HOW DID SHE DO IT?
When Mme. Calment was born, life expectancy — the average length of time that an individual can expect to live — was still less than 50 years.3 One of a handful of super centenarians worldwide, was her longevity and vigour due to a diet rich in olive oil, wine and chocolate, as she believed? Was it the complex interaction of heredity, lifestyle and environment: factors health professionals agree are important in determining whether an individual will have a long and healthy life? Or was it, perhaps, something even more basic?
Aging vastly increases our risk of heart disease, cancer and diabetes. The chances of dying from any of these diseases are remote when we are young but the risk doubles about every eight or nine years until middle age, when it significantly increases, and continues to redouble thereafter. Centenarian studies have found that though long-lived individuals are not immune to chronic diseases, they “get them later in life. If they get cancer, it does not kill them or it progresses very slowly.”4
When researchers looked for genes that might account for the extreme longevity among centenarians – the oldest of the old among us – they often found that genes that were strongly expressed in one long-lived population were not in others. “This is not particularly surprising, because genes don’t operate in isolation; they operate epigenetically in response to their environment. And when researchers look at different populations of individuals who have lived past 90 or 100, they are looking at people who managed to survive vastly different environmental stresses.”5
THE FOXO GENE
An important finding, however, is the role of the FOXO gene, which is regulated by the insulin/IGF signalling pathway – the same mechanism implicated for the apparent success of caloric restriction in promoting longevity and health. This piggybacks on increasing evidence from animal models suggesting that the insulin/IGF signalling pathway has a critical role in channelling bodily resources either towards reproduction and growth or toward bodily maintenance and repair, depending on the availability, or absence, of food. It also appears to have key significance in aging and longevity.6 The FOXO gene is the human analogue of the DAF-16 gene, long associated with longevity in nematodes. “In the worm, this gene makes a protein that looks much like the receptor for the hormone insulin. In humans, this hormone controls functions including food utilization pathways, glucose metabolism, and cell growth.”7
FOXO transcription factors are also at the interface of crucial cellular processes, orchestrating progressions of gene expression that regulate apoptosis, cell-cycle progression, and oxidative stress resistance. They can also facilitate the repair of damaged DNA.8 The connection between insulin, FOXO, oxidative stress and human longevity is particularly significant because, although not proven, the free radical theory of aging has long been thought to play a major role in aging. The free radical theory suggests aging results partly from damage to DNA, cells and tissues from cumulative exposure to reactive oxygen molecules. The FOXO gene may, therefore, represent the lynchpin linking insulin signalling, oxidative stress, and human aging and longevity.9
Genetic variation within the FOXO3A gene was found to be particularly strongly associated with human longevity in a recent landmark study that tracked the health of 8,000 Hawaiian men of Japanese ancestry.10 Long-lived men in this study, whose health had been monitored since the mid-1960s, also “presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function, despite significantly older ages than controls.”11 In fact, men with a G nucleotide (one of four chemical units comprising the double helix molecule of DNA) at a key location in the gene doubled their odds of living an average of 98 years, with some living as long as 106 years. Those who had two copies of the G nucleotide fared even better, almost tripling their odds of living nearly a century as well as presenting with lower incidences of heart disease, stroke and cancer.12 The same gene variant has also been found in studies of long-lived Germans, Italians, Ashkenazi Jews, and Chinese.13
All of us have FOXO genes. But few of us are likely to have the glittering “double G” variant, implicated as the key to super longevity in the Hawaiian study. Whether or not some variant within the FOXO group of genes, or another group of longevity-promoting genes, turns out to be the ultimate “fountain of youth” predisposing humans for longevity remains to be seen. What is clear is that the definitive aging clock moves by order of our genes. Only by finding those special genes and decoding their action can we hope to discover the key to extreme longevity and, perhaps, the means to end aging itself.
The path to agelessness, it seems, runs through our genes.
HEALTH SPAN VERSUS LIFE SPAN
That life span is, to a large extent, determined by our genes is not particularly surprising. It is not surprising because different animals age at different rates. Mice live about three years, but after two they are likely to begin showing signs of system breakdown or start developing cancer, organ failure and diabetes. The process of decrepitude begins for chimpanzees at about 30 years and humans typically take 60 or more. Clearly, some genetic mechanism must be driving the rate of species-specific aging.
Yet the degree to which genes influence our longevity startled many involved in recent aging studies of centenarians. When researchers questioned near-centenarians, it became apparent that there was a strong familial component to extreme longevity, with parents, grandparents or siblings also achieving exceptionally long lives. Perhaps less obvious was how little impact lifestyle choices had on individuals predisposed to extreme longevity. In one study, only two per cent were vegetarians, none exercised regularly, and 30 per cent were overweight or obese – this in the 1950s, when few were overweight or obese. Almost 30 per cent smoked two packs of cigarettes a day for more than 40 years.14 Mme. Calment, herself, quit smoking at age 117 only because she could no longer see well enough to light her cigarettes. Researchers with the Hawaiian study have suggested that “while non-genetic factors, including diet, physical activity, health habits and social influences are important, up to half of the variation in human lifespan might be explained by genetic differences.”15
This is not to say that smoking cigarettes won’t prematurely kill many of us not predisposed to extreme longevity, or that exercising regularly won’t increase our odds for a long and healthy life. In the words of one aging specialist, “if you want to live to be a healthy 80-year-old, you have to eat right and exercise” … “If you want to live to be a healthy 100-year-old, you have to have the right parents.”16
For most of us then, the goal is health span rather life span. Health span is the period of a person’s life during which they are generally healthy and free from serious or chronic illness whereas life span is the maximum biological limit any member of a species may live. Because aging is an underlying timing mechanism for all chronic diseases, by slowing the aging processes, the hope is that the chronic diseases associated with aging – diseases such as cancer, atherosclerosis, diabetes, osteoporosis, arthritis, Alzheimer’s, Parkinson’s – will be delayed or prevented altogether. Practices aimed at health span extension strive to lengthen the period of healthy aging before the onset of these chronic diseases and to optimize our body’s ability to maintain or return to homeostasis in response to challenges along the way.
The bottom line for most of us is that, unless you happen to be the happy owner of a longevity-promoting variant of the FOXO group of genes or some other as yet unidentified group of longevity-enhancing genetic markers, or are prepared to invest a lifetime in an extreme regimen of caloric restriction – so far, unproven in humans – the likelihood is that we will live to about 80 years.
The question then becomes “How do we maximize the number of healthy years before decrepitude and system failure kicks in”?
CHIROPRACTIC AND LONGEVITY
And what does chiropractic have to say about aging and longevity? For that we’d have to look at the philosophical roots of the profession. In DD Palmer’s original healing model – based, in part, on the doctrine of vitalism – Innate Intelligence recognizes that the body has intrinsic healing abilities. According to Dr. Marion McGregor, director of Year Two Education at the Canadian Memorial Chiropractic College, “Although all of healthcare is based on the notion of extending and optimizing health, the chiropractic profession has a rich history based on constructs intended to explain human life and health. Some have pointed out that the key concept in DD and BJ Palmer’s discussion of chiropractic philosophy and Innate is based in notions of life and death and on equilibrium of the body’s systems.”17
With the emergence of the modern era of science in health care, she notes, the concept of Innate became more clearly divisive within the chiropractic community.18, 19 “Today Innate exists as a paradigm challenged by unsolved puzzles and in competition with newer paradigms of care where evidence is more consistent with belief. What remains of this portion of chiropractic’s heritage is the notion of homeostasis shared by all practitioners seeking to alleviate human suffering.”
Nonetheless, notions of homeostasis and the body’s ability to heal itself fit squarely into modern concepts regarding wellness care and mind-body relationships – both of which can have profound implications on an individual’s health. In addition, factors such as the environment, lifestyle and diet all operate epigenetically to influence gene expression. Since the newest research suggests that exceptionally long lives are dictated largely by having the right genes, the objective for the majority of us becomes enhancing our health span rather than extreme longevity. As health-care professionals, chiropractors are well positioned to offer the best advice concerning health-promoting lifestyles – lifestyles which have the potential to extend our health span and to maximize our life expectancy.
In Part 4 of the Eternal Quest for Immortality, we conclude our exploration of longevity and aging with a look at the role of wellness in chiropractic practice, mind-body relationships and Immortality, Inc.
REFERENCES
1. Last WW I veteran, a waitress, dies in
U.K. CBC News/World. Feb. 7, 2012. Available from: http://www.cbc.ca/news/world/story/2012/02/07/ww1-last-veteran-dies.html
2. Worlds oldest person dies at 122. CNN/World. Aug. 4, 1997. Available
from:
http://articles.cnn.com/1997-08-04/world/9708_04_obit.oldest_1_oldest-person-arles-olive-oil?_s=PM:WORLD
3. National Institute on Aging, National Institutes of Health
(US). Aging under the microscope: a biological quest. 2006. NIH Pub. No. 02-2756:
4.
4. Taubes, G. The timeless and trendy effort to find – or create – the
Fountain of Youth. Discover Magazine. Oct, 2010. Available from: http://discovermagazine.com/2010/oct/12-timeless-trendy-effort-find-create-fountain-youth
5. Ibid.
6. Wilcox, BJ et al. FOXO3A genotype is
strongly associated with human longevity. PNAS, 2008, vol. 105, no. 37: 13987.
7. National Institute on Aging, National Institutes of Health (US).
Aging under the microscope: a biological quest. 2006. NIH Pub. No. 02-2756:
11.
8. Carter, ME and Brunet,
Anne. FOXO transcription factors, Current Biology, vol. 17, no. 4.
9.
Wilcox, BJ et al. FOXO3A genotype is strongly associated with human
longevity. PNAS, 2008, vol. 105, no. 37: 13987-8.
10.
Ibid: 13987.
11.
Ibid.
12. Roger
Highfield, Long-life gene that triples chance of living to 100 found. The
Telograph. 01
Sep 2008.
13. Taubes, G. The timeless and trendy
effort to find – or create – the Fountain of Youth. Discover Magazine. Oct,
2010. Available from: http://discovermagazine.com/2010/oct/12-timeless-trendy-effort-find-create-fountain-youth
14. Ibid.
15. Wilcox, BJ et
al. FOXO3A genotype is strongly associated with human longevity. PNAS, 2008,
vol. 105, no. 37: 13987.
16. Taubes, G. The timeless and
trendy effort to find – or create – the Fountain of Youth. Discover Magazine.
Oct, 2010. Available from: http://discovermagazine.com/2010/oct/12-timeless-trendy-effort-find-create-fountain-youth
17.
Wardwell, W. History and evolution of a new profession. St. Louis, Mo.:
Mosby Yearbook, 1992:181.
18. Kaptchuk TJ, Eisenberg, DM. Chiropractic:
origins, controversies, and contributions. Archives of Internal Medicine. 1998
Nov 9; 158:2217.
19. Morgan, L.
Innate intelligence: its origins and problems. Journal of the Canadian
Chiropractic Association. 1998 42(1):40.
Steve Zoltai is the collections development librarian and archivist for CMCC and is a member of the Canadian Chiropractic Historical Association. He was previously the assistant executive director of the Health Sciences Information Consortium of Toronto. He has worked for several public and private libraries and with the University of Toronto Archives. Steve comes by his interest in things historical honestly – he worked as a field archeologist for the Province of Manitoba. He can be contacted at szoltai@cmcc.ca.
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