• 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.


    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.


    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.


    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. 


    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.


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

  • March 15, 2010

    Older Americans have better cognitive health but worse overall health than their counterparts in England, two recent studies show. According to researchers, these health gaps could be due to differences in the prevalence of cardiovascular disease, depression, and other health factors, as well as differences in education, wealth, and access to health care.

    Older adults in the United States performed significantly better than their English counterparts on standard tests of cognitive function, shows a study published in BMC Geriatrics. The study—the first comparison of cognitive function in representative samples of older adults in the United States and England—looked at data on 8,299 Americans and 5,276 Britons, drawn from the 2002 waves of the NIA-funded Health and Retirement Study and the English Longitudinal Study of Ageing. All participants were non-Hispanic whites ages 65 and older.

    Overall, the difference in cognitive performance on tests of word recall and orientation was striking. On average, an 85-year-old American performed as well as a 75-year-old Briton. The U.S. advantage was greatest for people ages 85 and older, the age group on both sides of the Atlantic with the lowest scores on a 24-point cognitive scale.

    The difference in cognitive health could be due to several factors, the researchers write. Older adults in the United States are generally wealthier and better educated than those in England. They also reported lower levels of depressive symptoms. Higher levels of wealth and education and lower levels of depression have been associated with reduced risk of cognitive decline.

    In addition, the Americans had better cognitive health despite a higher prevalence of cardiovascular risk factors and disease—traits associated in some studies with poorer cognition. This result may be explained by the fact that the Americans were more likely than the British to take antihypertensive medications, which previous studies have suggested may help prevent cognitive decline.

    Another study, supported in part by the NIA and published in the American Journal of Public Health, found that older Americans had worse health than English and European seniors at all income levels, even though U.S. per-capita medical spending is two to three times higher than in Europe. Researchers compared the overall health status of non-Hispanic white adults ages 50 to 74 in the United States, England, and 10 European countries.

    Drawing on 2004 data from the Health and Retirement Study, the English Longitudinal Study of Ageing, and the Survey of Health, Ageing, and Retirement in Europe, the researchers found that Americans had the highest prevalence of chronic conditions and physical-function limitations. For example, 18 percent of Americans had heart disease, compared with 12 percent of Britons and 11 percent of Europeans. Poor Americans experienced the greatest health disadvantages compared with their overseas peers, but even well-off Americans reported health comparable to that of poorer Europeans.

    No single factor accounted for these disparities, the researchers note. Differences in behavioral risk factors such as smoking, obesity, physical activity, and alcohol consumption played a role, as did the prevalence of chronic disease, survival rates, and different health care systems. For instance, “the American medical system might be more focused on ameliorating the consequences of disease, with relatively less attention given to prevention,” the authors write.

    Together, the two studies point to the need for further international research that compares and explains the demographic, social, and health factors that account for differences in health status between older populations in different countries. These studies might help identify factors that could help improve the cognitive and physical health of growing elderly populations worldwide.


    Langa, K.M., et al. Cognitive health among older adults in the United States and England. BMC Geriatrics. 2009 June 25. 9:23.

    Avendano, M., et al. Health disadvantage of U.S. adults aged 50 to 74 years: a comparison of the health of rich and poor Americans with that of Europeans. Am J Public Health. 2009. 99(3):540–8.

  • March 15, 2010

    A recent study of long-lived naked mole rats calls into question the conventional theory that aging results from the accumulation of oxidative damage. Naked mole rats can live into their late 20s with steady levels of oxidative damage that begin at a young age. Another biological mechanism—resilient proteins that adapt to oxidative stress—may be the key to their successful aging, according to NIA-funded researchers at the University of Texas Health Science Center in San Antonio.

    The research reveals another exception to the widely accepted theory that oxidative damage to proteins and other molecules leads to aging. In naked mole rats, proteins sustain oxidative damage early on yet remain stable throughout the rats’ long lives, the scientists found. In contrast, proteins in short-lived mice show increasing levels of oxidative damage as they get older.

    In comprehensive testing and analysis of oxidation states of protein cysteines (sulfur-containing amino acids), the researchers found that, compared with mice, mole rats had higher levels of total cysteine and no age-related changes in cysteine oxidation during more than 20 years. The mole rats also showed unusual resistance to protein unfolding and lower levels of protein degradation during aging.

    The results suggest a new biochemical mechanism underlying longevity: the ability of oxidized proteins to maintain their structural stability and integrity.

    Reference: Pérez, V.I., et al. Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat. Proc Natl Acad Sci USA. 2009. 106(9):3059–64.

  • March 15, 2010

    Older adults with limited participation in social activities had a faster decline in motor function than those who had frequent social engagements, according to a report in the Archives of Internal Medicine. The study suggests that more frequent participation in social activities may slow older adults’ motor decline, which can lead to disability and other adverse health outcomes.

    In an NIA-supported study of 906 older adults without stroke, Parkinson’s disease, or dementia, researchers from Rush University Medical Center in Chicago found that each 1-point decrease in a participant’s social activity was associated with about a 33-percent more rapid rate of decline of motor function, a more than 40-percent increased risk of death, and a 65-percent increased risk of new disability. This decrease in social activity was equivalent to being about 5 years older at the start of the study. These associations held up after controlling for demographic and confounding factors such as chronic medical conditions, depression, and joint pain. 

    The researchers measured social activity based on frequency of activities such as going to restaurants and sporting events, attending religious services, traveling, playing bingo, and doing volunteer work. Motor function was measured by a composite score on 18 tests, including walking speed, grip strength, hip flexion, and turning.

    While higher levels of physical activity are known to be associated with a slower rate of decline in motor function, this study and others suggest a similar effect for social activity. “These findings may be particularly relevant for intervention strategies designed for older adults, for whom participation in physical activities may be constrained because of underlying health problems,” the authors conclude. However, more research is needed to confirm that increased social activity causes slower motor decline, not vice versa.


    Buchman, A.S., et al. Association between late-life social activity and motor decline in older adults. Arch Intern Med. 2009 June 22. 169(12):1139–46.

  • March 15, 2010

    The appropriate age at which to end prostate cancer screening is controversial, with different organizations issuing different recommendations. Data from a new study suggest that screening might be safely discontinued in men ages 75 and older who have prostate specific antigen (PSA) levels of less than 3 ng/ml—a cutoff point lower than that proposed in previous studies.

    PSA testing is common in older men despite evidence that those without aggressive prostate cancer are unlikely to benefit from diagnosis and treatment, write researchers from the Johns Hopkins School of Medicine and the NIA’s Intramural Research Program in Baltimore. To help weigh the risks and benefits of PSA testing in this population, they studied 849 men ages 40 and older who participated in the NIA Baltimore Longitudinal Study of Aging. Of the group, 122 had prostate cancer and 727 did not.

    Researchers determined the probability of high-risk prostate cancer developing in 5-year age groups starting at age 60, sorting the data by PSA cutoffs that ranged from less than 1 ng/ml to 3.5 ng/ml or greater. There is no PSA value below which a diagnosis of prostate cancer can be excluded, the authors note.

    Participants of all ages with a PSA of 3 ng/ml or more had an increasing probability of high-risk prostate cancer or death from the disease, the study found. Among those older than age 75, none with a PSA of less than 3 ng/ml died of prostate cancer, and only one got high-risk cancer. Of the older men with a PSA of 3 ng/ml or greater, 10 died of prostate cancer and 18 had high-risk disease.

    Men 75 to 80 years old with a PSA less than 3 ng/ml are unlikely to develop or die of aggressive prostate cancer during their lifetimes, the researchers conclude. This finding suggests that PSA testing might be safely discontinued for these men, avoiding unnecessary treatment.

    Reference: Schaeffer, E.M. et al. Prostate specific antigen testing among the elderly—when to stop? J Urol. 2009 April. 181:1606–14.

  • March 15, 2010

    A high degree of conscientiousness—the tendency to follow societal norms, plan, and be task and goal directed—has been shown to predict better physical health and functioning. In a recent study by researchers at the University of Illinois at Urbana-Champaign, older adults’ conscientiousness also seemed to influence the health status of their spouses, an effect called “compensatory conscientiousness.”

    Another personality trait, neuroticism, is associated with poorer health and physical limitations, the researchers found. Unlike conscientiousness, neuroticism—an enduring tendency to experience negative emotional states, often accompanied by anxiety or stress—did not predict a spouse’s or partner’s health status.

    However, people who scored high in both neuroticism and conscientiousness were healthier than others, perhaps because the heightened sense of concern worked synergistically to result in a higher degree of awareness of a spouse’s health. The wives of men with this combination of personality traits reported better health than other women. A husband who is anxious about his wife’s health could be driven to activities that improve her health, the authors explain. However, this compensatory effect did not appear for husbands of women with high neuroticism and conscientiousness.

    Looking at 2,006 self-reports from 2,203 couples who participated in the NIA-funded Health and Retirement Study of people ages 50 and older, the researchers found that older adults’ conscientiousness predicted their spouses’ health outcomes above and beyond the spouses’ own personality. “These results suggest that a conscientious partner is beneficial to an individual’s health no matter how conscientious that individual is,” they conclude. “Partners high in conscientiousness might be more reliable and consistent providers of support and might be a source of more constructive advice and feedback about health-related issues.”


    Roberts, B.W., et al. Compensatory conscientiousness and health in older couples. Psychol Sci. 2009. 20(5):553–9.