Announcements

  • May 12, 2009

    Researchers at the Pennington Biomedical Research Center in Baton Rouge, LA, have shown that when people significantly reduce their calorie intake, they undergo a metabolic adaptation that results in a slower metabolic rate. The slower metabolic rate results in a behavioral adaptation in which individuals become less physically active.

    The researchers examined data from 48 overweight people who followed 1 of 4 diet regimens for 6 months: a 25-percent calorie restriction (CR) diet, a low-calorie diet, a 12.5-percent CR diet plus 12.5-percent aerobic exercise program, or a normal diet. While the first three groups lost weight, after 6 months, the CR and low-calorie diet groups showed a reduction in their basal metabolic rate, accompanied by reduced physical activity. The CR plus physical activity group also lost weight but did not undergo a metabolic adaptation.

    This is the first study to measure metabolic rate and energy expenditure precisely through the use of doubly labeled water and indirect calorimetry. The study also shows that long-term calorie reduction without increased exercise can result in a lower metabolic rate. The researchers note that the data “suggest potential mechanisms by which CR causes large inter-individual variability in the rates of weight loss and how exercise may influence weight loss and weight loss maintenance.”

    Reference:

    Redman, L.M., et al. Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLoS ONE. 2009. 4(2):e4377.

  • May 12, 2009

    The protein Lrp5, long known to play a critical role in bone remodeling, appears to exert its effects through the gut, not directly through the bone, as previously thought, according to preclinical research published in Cell. The findings could suggest new therapeutic approaches to increase bone mass in older adults and others with osteoporosis.

    In bone remodeling, old bone is resorbed by specialized cells, called osteoclasts, and new bone is formed by other specialized cells, called osteoblasts. Lrp5 (low-density lipoprotein receptor-related protein 5) is an important regulator in the underlying molecular process. A decrease in its function can lead to osteoporosis, while overproduction results in high bone mass syndromes in humans.

    Scientists have long believed that Lrp5 controls bone mass through signaling in the Wnt pathway in bone osteoblasts. However, NIH-supported researchers at Columbia University found that Lrp5 works indirectly through the gut. In a study in mice, they found that Lrp5 inhibits expression of the gene Tph1, which encodes an enzyme that, in turn, helps synthesize serotonin in the duodenum. The resulting decrease in serotonin production was associated with increased bone mass in mice. Conversely, mice deficient in Lrp5 produced excess serotonin in the gut and developed low bone mass. Furthermore, turning off Lrp5 in the gut, but not bone, affected serotonin levels and, through serotonin, bone mass.

    Reference:

    Yadav, V.K., et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008 Nov 28. 135:825–37.

  • May 12, 2009

    NIA-funded researchers have found that happiness is not an isolated phenomenon, unique to an individual, but rather spreads through social networks. Using data from the Framingham Heart Study, Drs. Nicholas Christakis of Harvard Medical School and James Fowler of the University of California, San Diego examined how social ties influence individuals’ mood and sense of well-being. They found that people who are surrounded by happy people are more likely to be happy themselves.

    The researchers looked at the happiness of nearly 5,000 individuals in the Framingham cohort during a period of 20 years. They found that one person’s happiness triggers a chain reaction that benefits not only their friends, but their friends’ friends, and their friends’ friends’ friends, with the effect lasting for up to a year.

    The effects are limited by both time and space. The closer a friend lives to a person, the stronger the effect. As distance increases, the effect decreases. This explains why friends who are next-door neighbors have an effect, but those who live around the block do not. Interestingly, the effects did not apply to co-workers and were stronger between same-sex than between opposite-sex pairs.

    This is the third major network analysis by these researchers that shows how social context affects health. The two previous studies, published in the New England Journal of Medicine, described the social network effects in obesity and smoking cessation.

    Reference:

    Fowler, J.H., and Christakis, N.A. Dynamic spread of happiness in a large social network: longitudinal analysis over 20 years in the Framingham Heart Study. BMJ. 2008 Dec 4. 337:a2338.

  • May 12, 2009

    The threat of smallpox resulting from bioterrorism has prompted a reassessment of the current population’s level of immunity. A recent study by researchers in the NIA’s Intramural Research Program shows that older adults who either had smallpox as children or were vaccinated years ago remain immune to the disease and would be unlikely to benefit from new vaccinations.

    Given the limited supply of smallpox vaccine in the United States, it makes sense to immunize people most at risk in the event of smallpox exposure, researchers wrote in the American Journal of Medicine. That population includes individuals born after 1972—about the time when routine smallpox vaccination ended in the United States—but not many older adults, they concluded in a study of 246 participants from the Baltimore Longitudinal Study of Aging.

    Older adults who were vaccinated at least once appear to remain immune, according to an analysis of more than 800 serum samples that had been stored for 13 to 88 years after vaccination. The researchers, led by Drs. Dan Longo and Dennis Taub, determined that levels of vaccine-specific antibody titers and neutralizing antibodies remained high enough to indicate continued immunity in 209 individuals who had been vaccinated, based on the comparable levels of their antibodies and those of 8 participants who had had smallpox as children. It is known that survivors of smallpox have lifelong immunity to it. Multiple vaccinations conferred only marginally higher protection than a single one.

    Reference:

    Taub, D.D., et al. Immunity from smallpox vaccine persists for decades: a longitudinal study. Am J Med. 2008 Dec. 121:1058–64.

  • May 12, 2009

    The prevalence of meniscal tears in adults increases with age, but often they are not accompanied by knee pain or other symptoms, according to a recent study supported in part by the NIA. Researchers led by Dr. Martin Englund of the Boston University School of Medicine sought to determine the prevalence of damage to menisci, the tissue-filled disks between knee bones. A random sample of 991 adults ages 50–90 in Framingham, MA, filled out questionnaires about symptoms and underwent magnetic resonance imaging (MRI) of their right knees.

    The presence of meniscal damage detected by MRI averaged 35 percent overall and rose with age—from 19 percent in women and 32 percent in men between the ages of 50 and 59 to 51 percent in women and 56 percent in men between the ages of 70 and 90. Most participants with meniscal tears (61 percent) reported no pain, aching, or stiffness during the month before the study. In people with knee osteoarthritis, the prevalence of a meniscal tear was 63 percent among those with knee pain, aching, or stiffness on most days and 60 percent among those without these symptoms.

    These epidemiologic findings emphasize the difficulties in appropriately interpreting MRI findings of the knee and the relationship of meniscal damage to knee pain. As the researchers note, the study suggests that incidental meniscal findings detected on MRI are likely to be frequent in clinical practice. Clinicians who order MRI of the knee should take into account the high prevalence of incidental tears when interpreting the results and planning therapy.

    Reference:

    Englund, M., et al. Incidental meniscal findings on knee MRI in middle-aged and elderly persons. N Engl J Med. 2008 Sept 11. 359:1108-15.

  • May 12, 2009

    Scientists have found a mechanism involving the protein SIRT1 that links DNA damage with age-related changes in gene expression. The study in mice has striking parallels with findings from studies of a similar mechanism in yeast.

    Past research has shown that in yeast, the protein Sir2—known for its part in extending life—plays an important role in stabilizing gene function. When DNA damage occurs, Sir2 abandons this role to assist with DNA repair. Without Sir2’s control, genes become unstable and render the yeast sterile, a characteristic associated with aging.

    NIH-funded investigators led by Dr. David A. Sinclair of Harvard Medical School in Boston looked at a parallel process in mouse stem cells. They found that SIRT1, the mammalian equivalent of Sir2, helps control gene activity—except when DNA is damaged. In that case, it leaves its normal role to help repair DNA. The resulting changes in gene activity in stem cells are similar to those seen in the brains of aging mice.

    Researchers also found longer survival and a lower incidence of tumors in mice with overexpressed SIRT1 than in mice with normal SIRT1 levels. These results indicate that increasing SIRT1 activity or quantity can increase genomic stability and is associated with longer life.

    Reference:

    Oberdoerffer, P., et al. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell. 2008 Nov 28. 135:907-18.

  • May 12, 2009

    Two recent NIA-funded studies used novel imaging techniques to explore the possible connection between the buildup of beta-amyloid protein deposits in the brains in living people and the risk of developing Alzheimer’s disease (AD). Abnormal deposits of amyloid in the brain are hallmarks of Alzheimer’s and, until recently, could only be confirmed at autopsy. But as shown in these two studies, researchers are using techniques involving PET (positron emission tomography) scans and tracers to image amyloid deposits in people who are symptom free.

    One study found large numbers of beta-amyloid protein deposits in the brains of cognitively normal older adults, suggesting that the deposits alone may not be enough to disrupt cognitive function. The other study showed that known genetic markers for the disease did indeed correlate with greater deposits of amyloid, suggesting that the PET method might eventually result in better and earlier detection of the disease.

    In the first study, reported in the Archives of Neurology, researchers used PET with the tracer element Pittsburgh Compound B (PiB) to image the brains of 43 adults, 65 to 88 years old, who did not have clinical AD or mild cognitive impairment, a condition that often precedes AD. They found that the 9 participants with beta-amyloid deposits in at least one brain area performed as well on cognitive tests as the 29 amyloid-negative participants and the 5 participants with “intermediate” evidence of amyloid deposits.

    The finding that an older person with “significant amyloid burden” can be cognitively normal suggests a high level of cognitive reserve or that beta-amyloid deposition alone does not lead to AD, write the authors, led by Dr. William E. Klunk of the University of Pittsburgh School of Medicine. Alternatively, some of these individuals may go on to develop AD—in which case PET may be useful in finding signs of AD before clinical symptoms appear. The findings with PiB mirror those previously found in clinicopathological studies, where a proportion of clinically normal people were found to have significant amyloid deposits in their brains after death.

    In the second study, published in the Proceedings of the National Academy of Sciences, researchers, led by Dr. Eric Reiman of the Banner Alzheimer’s Institute in Phoenix, conducted PET scans using PiB in 28 cognitively normal older people and correlated the results with the presence of the apolipoprotein E (APOE) ε4 allele, a known risk factor for AD.

    The researchers found progressively higher levels of beta-amyloid deposits in carriers with one and two copies of the APOE ε4 than in the noncarriers. They concluded that their findings “support the possibility of using fibrillar beta-amyloid imaging, along with other biomarkers of beta-amyloid, tau, and neuronal pathology and other risk factors, in the preclinical detection and tracking of AD and the evaluation of promising prevention therapies.” Previous autopsy studies have shown that ApoE ε4 carriers have higher levels of amyloid pathology in their brains at  death.

    References:

    Aizenstein, H.J., et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008 Nov. 65(11):1509–17.

    Reiman, E.M, et al. Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA. 2009 Apr 21. 106(16):6820-25.

  • May 12, 2009

    A recent article about a population-based study in England reports that exposure to secondhand smoke could increase the odds of older nonsmokers becoming cognitively impaired.

    In work funded in part by the NIA, researchers measured levels of salivary cotinine, a nicotine metabolite that indicates exposure to secondhand smoke, in 4,809 adults ages 50 and older. All participants were nonsmokers who did not use nicotine products but were exposed to smoking—at home, in the workplace, or in other locations. The sample was drawn from the multiyear Health Survey for England and the 2002 wave of the English Longitudinal Study of Ageing.

    Individuals with the highest concentrations of cotinine—and thus more exposure to secondhand smoke—were more likely than those with lower concentrations to become cognitively impaired, as measured by their performance on neuropsychological tests. Dr. David J. Llewellyn of the University of Cambridge and colleagues found that these results held after controlling for risk factors for cognitive decline, including age, education, and the presence of cardiovascular disease. Perhaps surprisingly, there was even a trend toward stronger cognitive impairment in those who had never smoked.

    The authors note that the results are consistent with previous findings that active smoking may raise the risk of cognitive impairment, but further research is needed to establish if and how secondhand smoke might cause cognitive decline.

    Reference:

    Llewellyn DJ, et al. Exposure to secondhand smoke and cognitive impairment in non-smokers: national cross sectional study with cotinine measurement. BMJ. 2009 Feb 12. 338:b462.

  • May 12, 2009

    Two recent imaging studies shed light on how menopausal hormone therapy (MHT) may affect the brains of older women. Previous studies showed that MHT increased the likelihood that older women would have difficulty with thinking skills and memory and develop dementia or cognitive impairment.

    In the first study, researchers with the Women’s Health Initiative Memory Study-MRI (WHIMS-MRI), an ancillary study of the Women’s Health Initiative (WHI) hormone therapy clinical trials, took MRI brain scans of approximately 1,400 women 79 to 89 years of age 1 to 4 years after the WHI hormone trials ended. They found that women who had taken MHT had smaller brain volumes in two brain areas than women who had taken a placebo. Brain volume was lower in the frontal lobe and in the hippocampus, areas involved in thinking and memory skills. Loss of volume in the hippocampus is a risk factor for dementia.

    “Our findings suggest one possible explanation for the increased risk for dementia in older women who had previously taken MHT in the WHIMS,” said lead author Dr. Susan Resnick of the NIA’s Intramural Research Program. “The findings also suggest that hormone therapy in older postmenopausal women has a negative effect on brain structures important in maintaining normal memory functioning. However, this negative effect was most pronounced in women who already may have had some memory problems before using MHT, suggesting that the therapy may have accelerated a neurodegenerative disease process that had already begun.”

    Dr. Resnick emphasized that the women in this study were randomly assigned to MHT later in life than the usual period of treatment around the time of the menopausal transition. It remains unclear whether earlier MHT given only during the period of most intense menopausal symptoms is associated with poorer cognition.

    In the second study, researchers analyzing the MRI scans found that MHT was not linked to an increase in volumes of small vascular lesions in the brain that are often the first sign of cerebrovascular disease. Lead author Dr. Laura Coker of Wake Forest University noted that the negative effects of MHT on cognitive skills may not be related primarily to vascular disease but to neurodegeneration, which is supported by the first study’s findings of brain atrophy. 

    References:

    Resnick, S.M., et al. Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study. Neurology. 2009 Jan 13. 72(2):135-42.

    Coker, L.H., et al. Postmenopausal hormone therapy and subclinical cerebrovascular disease: the WHIMS-MRI Study. Neurology. 2009 Jan 13. 72(2):125-34.

  • March 15, 2010

    Specific personality characteristics may be important to successful aging, according to researchers who studied a group of adult children of centenarians. Other studies have shown that these personality traits promote good health and minimize damaging characteristics.

    The children of people who lived to 100 years or more are generally a model of healthy aging, with lower mortality and lower prevalence of chronic diseases than other members of their birth cohort. In this study, researchers led by Dr. Thomas T. Perls of the Boston University Medical Center found that such offspring are more extraverted and less neurotic than other members of their birth cohort.

    Using the NEO Five-Factor Inventory, a 60-item, self-report questionnaire, the researchers measured five personality characteristics—neuroticism, extraversion, openness, agreeableness, and conscientiousness—in 246 offspring of centenarians with a mean age of 75 years. Both men and women scored in the low range for neuroticism and in the high range for extraversion.

    The researchers note that the low neuroticism and higher extraversion levels may confer health benefits. For example, people who are lower in neuroticism may be able to manage stressful situations more effectively than those with higher neuroticism levels. Similarly, high extraversion levels have been associated with greater subjective well-being, vitality, and longevity.

    Reference:

    Givens, J.L., et al. Personality traits of centenarian’s offspring. J Am Geriatr Soc. 2009. 57:683–85.

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