Tag Archives: aging

Small declines in agility, facial features may predict risk of dying (Epidemiology)

Photo source: Shutter Stock

Photo source: Shutter Stock

By B. Rose Huber, Woodrow Wilson School of Public and International Affairs

A new study from Princeton University shows that health assessments made by medically untrained interviewers may predict the mortality of individuals better than those made by physicians or the individuals themselves.

Features like forehead wrinkles and lack of agility may reflect a person’s overall health and risk of dying, according to recent health research. But do physicians consider such details when assessing patients’ overall health and functioning?

In a survey of approximately 1,200 Taiwanese participants, Princeton University researchers found that interviewers — who were not health professionals but were trained to administer the survey — provided health assessments that were related to a survey participant’s risk of dying, in part because they were attuned to facial expressions, responsiveness and overall agility.

The researchers report in the journal Epidemiology that these assessments were even more accurate predictors of dying than assessments made by physicians or even the individuals themselves. The findings show that survey interviewers, who typically spend a fair amount of time observing participants, can glean important information regarding participants’ health through thorough observations.

“Your face and body reveal a lot about your life. We speculate that a lot of information about a person’s health is reflected in their face, movements, speech and functioning, as well as in the information explicitly collected during interviews,” said Noreen Goldman, Hughes-Rogers Professor of Demography and Public Affairs in the Woodrow Wilson School.

Together with lead author of the paper, Princeton Ph.D. candidate Megan Todd, Goldman analyzed data collected by the Social Environment and Biomarkers of Aging Study (SEBAS). This study was designed by Goldman and co-investigator Maxine Weinstein at Georgetown University to evaluate the linkages among the social environment, stress and health. Beginning in 2000, SEBAS conducted extensive home interviews, collected biological specimens and administered medical examinations with middle-aged and older adults in Taiwan. Goldman and Todd used the 2006 wave of this study, which included both interviewer and physician assessments, for their analysis. They also included death registration data through 2011 to ascertain the survival status of those interviewed.

The survey used in the study included detailed questions regarding participants’ health conditions and social environment. Participants’ physical functioning was evaluated through tasks that determined, for example, their walking speed and grip strength. Health assessments were elicited from participants, interviewers and physicians on identical five-point scales by asking “Regarding your/the respondent’s current state of health, do you feel it is excellent (5), good (4), average (3), not so good (2) or poor (1)?”

Participants answered this question near the beginning of the interview, before other health questions were asked. Interviewers assessed the participants’ health at the end of the survey, after administering the questionnaire and evaluating participants’ performance on a set of tasks, such as walking a short distance and getting up and down from a chair. And physicians — who were hired by the study and were not the participants’ primary care physicians — provided their assessments after physical exams and reviews of the participants’ medical histories. (Study investigators did not provide special guidance about how to rate overall health to any group.)

In order to understand the many variables that go into predicting mortality, Goldman and Todd factored into their statistical models such socio-demographic variables as gender, place of residence, education, marital status, and participation in social activities. They also considered chronic conditions, psychological wellbeing (such as depressive symptoms) and physical functioning to account for a fuller picture of health.

“Mortality is easy to measure because we have death records indicating when a person has died,” Goldman said. “Overall health, on the other hand, is very complicated to measure but obviously very important for addressing health policy issues.”

Two unexpected results emerged from Goldman and Todd’s analysis. The first: physicians’ ratings proved to be weak predictors of survival. “The physicians performed a medical exam equivalent to an annual physical exam, plus an abdominal ultrasound; they have specialized knowledge regarding health conditions,” Goldman explained. “Given access to such information, we anticipated stronger, more accurate predictions of death,” she said. “These results call into question previous studies’ assumptions that physicians’ ‘objective health’ ratings are superior to ‘subjective’ ratings provided by the survey participants themselves.”

In a second surprising finding, the team found that interviewers’ ratings were considerably more powerful for predicting mortality than self-ratings. This is likely, Goldman said, because interviewers considered respondents’ movements, appearance and responsiveness in addition to the detailed health information gathered during the interviews. Also, Goldman posits, interviewer ratings are probably less affected by bias than self-reports.

“The ‘self-rated health’ question is religiously used by health researchers and social scientists, and, although it has been shown to predict mortality, it suffers from many biases. People use it because it’s easy and simple,” Goldman continued. “But the problem with self-rated health is that we have no idea what reference group the respondent is using when evaluating his or her own health. Different ethnic and racial groups respond differently as do varying socioeconomic groups. We need other simple ways to rate individual health instead of relying so heavily on self-rated health.”

One way, Goldman suggests, is by including interviewer ratings in surveys along with self-ratings: “This is a straightforward and cost-free addition to a questionnaire that is likely to improve our measurement of health in any population,” Goldman said.

The paper, “Do Interviewer and Physician Health Ratings Predict Mortality? A Comparison with Self-Rated Health,” first appeared online in Epidemology in August 2013. The article also will be featured in the November print edition. The research was conducted with the assistance of colleagues at Princeton’s Office of Population Research, Georgetown University and the Bureau of Health Promotion in the Taiwan Department of Health.

Read the abstract.

Todd MA, Goldman N. Do interviewer and physician health ratings predict mortality?: a comparison with self-rated health. Epidemiology. 2013 Nov;24(6):913-20. doi: 10.1097/EDE.0b013e3182a713a8.

 

DNA Gridlock – Cells undo glitches to prevent mutations (Nature)

By Catherine Zandonella, Office of the Dean for Research

G4 Quadruplex

The diagram shows a G-quadruplex (G4) on the upper of the two strands that make up DNA. The purple shape represents DNA polymerase, which is blocked by the G4 in its attempt to copy DNA. Regions of the genome that are especially susceptible to forming G-quadruplexes are ones rich in guanine, which is one of the four nucleotides, designated by the letters G, A, C, and T, in DNA. Adapted from Nature Genetics, 2012.

Roughly six feet of DNA are packed into every human cell, so it is not surprising that our genetic material occasionally folds into odd shapes such as hairpins, crosses and clover leafs. But these structures can block the copying of DNA during cell division, leading to gene mutations that could have implications in cancer and aging.

Now researchers based at Princeton University have uncovered evidence that cells contain a built-in system for eliminating one of the worst of these roadblocks, a structure known as a G-quadruplex. In a paper published earlier this month in Nature, a group of researchers led by Princeton’s Virginia Zakian reported that an enzyme known as the Pif1 helicase can unfold these structures both in test tubes and in cells, bringing DNA replication back on track.

Given that Pif1 mutations have been associated with an increased risk of breast cancer, Zakian said, the study of how Pif1 ensures proper DNA replication could be relevant to human health. Zakian is Princeton’s Harry C. Wiess Professor in the Life Sciences.

Most DNA is made of up of two strands twisted about each other in a way that resembles a spiral staircase. Every time a cell divides, each DNA molecule must be duplicated, a process that involves unwinding the staircase so that an enzyme known as DNA polymerase can work down each strand, copying each letter in the DNA code. During this exposed period, regions of the unwound single strands can fold into G-quadruplexes (see diagram).

Like a car that encounters a pile-up on an Interstate, the DNA polymerase halts when it encounters a G-quadruplex, explained Matthew Bochman, a postdoctoral researcher who was a co-first author with Katrin Paeschke, now an independent investigator at University of Würzburg in Germany. The work also included Princeton graduate student Daniela Garcia.

“The DNA that is folded into a G-quadruplex cannot be replicated, so essentially it is skipped,” Bochman said. “Failure to copy specific areas of DNA that you really need is a serious problem, especially in regions that control genes that either suppress or contribute to cancer,” Bochman said.

Last year, the Zakian group in collaboration with human geneticists at the University of Washington reported that a mutation in human Pif1 is associated with an increased risk of breast cancer, suggesting that the ability to unwind G-quadruplexes could be important for protecting against cancer. The finding was published in the journal PLoS One.

G-quadruplexes could also be implicated in the process of aging, according to the researchers. The structures are thought to form at the ends of chromosomes in regions called telomeres, said Zakian, an expert on telomere biology.  Damaged or shortened telomeres are associated with premature aging and cancer.

To explore the role of Pif1 helicases in tackling G-quadruplexes, Bochman and Paeschke purified Pif1 helicases from yeast and bacteria and found that in test tubes, all of the Pif1 helicases unwind G-quadruplex structures extremely fast and very efficiently, much better than other helicases tested in the same way.

Next, these investigators set up an experiment to determine if Pif1 acts on G-quadruplexes inside cells. Using a system that could precisely evaluate the effects of G-quadruplex structures on the integrity of chromosomes, the researchers found that normal cells had no problem with the addition of a G-quadruplex structure, but when cells lack Pif1 helicases, the G-quadruplex induced a high amount of genome instability.

“To me, the most remarkable aspect of the study was the demonstration that Pif1-like helicases taken from species ranging from bacteria to humans and placed in yeast cells can suppress G-quadruplex-induced DNA damage,” Zakian said. “This finding suggests that resolving G-quadruplexes is an evolutionarily conserved function of Pif1 helicases.”

The Zakian lab also found that replicating through G-quadruplexes in the absence of Pif1 helicases results not only in mutations of the DNA at the site of the G-quadruplex but also in intriguing “epigenetic” effects on expression of nearby genes that were totally unexpected. Epigenetic events cause changes in gene expression that are inherited, yet they do not involve loss or mutation of DNA. Graduate student Daniela Garcia has proposed that the epigenetic silencing of gene expression that occurs near G-quadruplexes in the absence of Pif1 helicases is a result of the addition or removal of molecular tags on histones, which are proteins that bind DNA and regulate gene expression. This hypothesis is currently being studied.

The study involved contributions from Petr Cejka and Stephen C. Kowalczykowski of the University of California-Davis, and Katherine Friedman of Vanderbilt University.

Read the abstract.

Paeschke, Katrin, Matthew L. Bochman, P. Daniela Garcia, Petr Cejka, Katherine L. Friedman, Stephen C. Kowalczykowski & Virginia A. Zakian. Pif1 family helicases suppress genome instability at G-quadruplex motifs. Nature. 2013. doi:10.1038/nature12149.

This research was supported by the National Institutes of Health (V.A.Z., GM026938-34; S.C.K.GM041347), the National Science Foundation (K.L.F., MCB-0721595), the German Research Foundation (DFG), the New Jersey Commission on Cancer Research (K.P.) and the American Cancer Society (M.L.B., PF-10-145-02-01).