The New England Centerian Study

Hypothesis The New England Centenarian Study (NECS) is based on our conviction that centenarians are a select group of people who have a history of aging relatively slowly and who have either markedly delayed or entirely escaped diseases normally associated with aging such as Alzheimers disease, cancer, stroke and heart disease (1).

History The study began in 1994 as a population-based study of all centenarians living within 8 towns in the Boston area. The prevalence of Alzheimer's Disease and other dementias in centenarians was the focus. Given that the prevalence of centenarians in industrialized countries is approximately one centenarian per 10,000 people in the population, at any particular time we were studying approximately 46 centenarians within a total population of 460,000 people (2). The NECS has gone on to enroll centenarians from throughout the United States and other countries and has grown to be the largest comprehensive study of centenarians in the world. There are currently 1,500 subjects to-date, including centenarians, their siblings and children (in their 70s and 80s) and younger controls. The study previously received funding from the Alzheimer's Association, and the Ellison Medical Foundation and currently receives funding from the National Institute of Aging (NIA), an institute of the National Institutes of Health (NIH). All studies are approved by the Boston University Medical Center Institutional Review Board.

The Older You Get, The Healthier You've Been
Consistent with our hypothesis that centenarians markedly delay or even escape age-associated diseases (e.g. heart attack, stroke, cancer, diabetes, Alzheimer's disease), we noted that 90% of them were functionally independent the vast majority of their lives up until the average age of 92 years and 75% were the same at an average age of 95 years. Centenarians disprove the perception that "the older you get the sicker you get", centenarians teach us that the older you get the healthier you've been (3).

Predictors of Reaching 100
Once it truly became apparent that living to 100 was a terrific advantage, not just in years of survival but importantly in many more years of quality life, we set out to understand what factors the centenarians had in common that might explain such an advantage. Not all centenarians are alike. They vary widely in years of education (no years to post-graduate), socioeconomic status (very poor to very rich), religion, ethnicity and patterns of diet (strictly vegetarian to extremely rich in saturated fats). However, the centenarians we have studied do have a number of characteristics in common:

• Few centenarians are obese. In the case of men, they are nearly always lean.
• Substantial smoking history is rare.
• A preliminary study suggests that centenarians are better able to handle stress than the majority of people.
• Our finding that many centenarians (30%) had no significant changes in their thinking abilities disproved the expectation by many that all centenarians would be demented (4). We also discovered that Alzheimer's Disease was not inevitable. Some centenarians had very healthy brains (5).
• Many centenarian women have a history of bearing children after the age of 35 years and even 40 years. From our studies, a woman who naturally has a child after the age of 40 has a 4 times greater chance of living to 100 compared to women who do not (6). It is probably not the act of bearing a child in one's forties that promotes long life, but rather, doing so may be an indicator that the woman's reproductive system is aging slowly and that the rest of her body is as well. Such slow aging and the avoidance or delay of diseases that adversely impact reproduction would bode well for the woman's subsequent ability to achieve very old age.
• At least 50% of centenarians have first-degree relatives and/or grandparents who also achieve very old age, and many have exceptionally old siblings. Male siblings of centenarians have an 11 times greater chance than other men born around the same time of reaching age 97 years and female siblings have an 8½ greater chance than other females also born around the same time of achieving age 100 (7).
• Many of the children of centenarians (age range of 65 to 82 years) appear to be following in their parents' footsteps with marked delays in cardiovascular disease, diabetes and overall mortality (8).
• Exceptional longevity runs strongly in families. Brothers and sisters of centenarians maintain half the mortality rate of other people born in the same time period, from age 20 all the way into extreme old age. The cumulative effect of this year-to-year survival advantage is that the brothers have a 17 times greater chance of living to 100 and the sisters have an 8 times greater chance (9).
  

Our Studies and Collaborators

The New England Centenarian Study closely collaborates with Dr. Lindsay Farrer, an eminent geneticist at Boston University School of Medicine, who is helping us decipher the genetics underlying the tremendous survival advantages we are observing among the children of centenarians who generally have half the risk of heart disease, diabetes and stroke and one quarter the mortality rate compared to their peers.

We are particularly interested in how centenarians are able to markedly delay or in some cases escape Alzheimer's disease. We perform detailed and annual neuropsychological examinations on centenarians living within 3-4 hours of Boston. A number of these subjects have indicated their willingness to donate their brains for neuropathological studies once they pass away, thus allowing our scientific collaborators to better characterize the health of the centenarians' exceptionally old brains.

We also expend significant resources to disseminate our findings and to advocate for older people, providing an optimistic and enabling view of aging. Most people have the genetic makeup to live into their mid to late eighties in very good health, and like centenarians, compress the time they are sick towards the end of their lives. Much of their ability to do so depends upon healthy behaviors including a diet conducive to being lean, not smoking, and strength training exercise. Promoting this philosophy will have a much greater impact now on many more people than our genetic research. Our collaborations with Dr. Robert Butler and the International Longevity Center have been extremely fruitful in furthing this mission (10-12)

References:
1. Perls TT. The Oldest Old. The Scientific American, 1995;272:70-75.
2. Perls TT, Bochen K, Freeman M, Alpert L, Silver MH. The New England Centenarian Study: validity of reported age and prevalence of centenarians in an eight town sample. Age and Ageing.1999;28(2):193-197.
3. Hitt R, Young-Xu Y, Perls T. Centenarians: The older you get, the healthier you've been. Lancet, 1999;354 (9179):652
4. Silver, M.H., Jilinskaia, E., Perls, T.T. Cognitive functional status of age-confirmed centenarians in a population-based study. Journal of Gerontology, Psychol Sci 2001;56B:P134-P140.
5. Silver MH, Newell K, Brady C, Hedley-Whyte ET, Perls TT. Distinguishing between neurodegenerative disease and disease-free aging: correlating neuropsychological evaluations and neuropathological studies in centenarians. Psychosomatic Medicine 2002;64:493-501.
6. Perls T, Alpert L, Fretts R. Middle aged mothers live longer. Nature 1997;389:133.
7. Perls T, Kunkel L, Puca A. The Genetics of Exceptional Human Longevity. J Am Geriatr Soc 2002;50:359-368.
8. Terry DF, Wilcox M, McCormick MA, Lawler E, Perls TT. Cardiovascular Advantages Among the Offspring of Centenarians. J Gerontol Med Sci 2004;59:M385-389
9. Perls TT, Wilmoth J, Levenson R, Drinkwater M, Cohen M, Bogan H, Joyce E, Brewster S, Kunkel L, Puca A. Life-Long Sustained Mortality Advantage Of Siblings Of Centenarians. Proc Natl Acad Sci USA 2002;99:8442-8447.
10. Butler RN, Rothman D, Harman SM, Fossel M, Heward CB, Olshansky SJ, Perls TT, Rothman SM, West M, Wright WE, Warner HR. “Is There An Anti-Aging” Medicine? J Gerontol: Biol Sci 2002;57:B333-B338.
11. Birren JE, Butler RN, Cotman CW et al. Achieving and maintaining cognitive vitality with aging. Institute for the Study of Aging and the International Longevity Center, New York, 2001.
12. Butler RN, Sprott RL, Austad SN, Barzilai N, Braun A, Helfand S, Larsen P, McCormick AM, Miller RA, Perls T, Shuldiner A, Warner HR. Longevity genes: From primitive organisms to humans. International Longevity Center, New York, 2002.

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