Telomere Disclosure and Impact on Psychological Distress and Health Behaviors
Condition: Telomere Length, Mean Leukocyte
Study type: Interventional

Summary: 
      There is now a critical mass of data linking health to telomere length, and blood telomere
      length is starting to become a commercially available measure, with several companies either
      offering or planning to offer this measure. With the growing intrigue and interest in
      telomeres and its commercial measurement, it is becoming increasingly important to understand
      the psychological and behavioral impact of receiving information about one's own telomere
      length. Therefore, the primary purpose of this study is to provide results of blood telomere
      length (from immune cells) to individuals, and to examine the subsequent psychological and
      lifestyle factors associated with learning one's personal results. Specifically, the
      investigators will assess if providing both telomere length and educational material on how
      cell aging is related to health and how it is modifiable, might lead to improvements in
      salutary health behaviors, and consequently, changes in telomere length.

      A secondary goal of the study is methodological in nature. Human studies have mainly been
      limited to immune cells from blood, which requires a blood draw. The relation between blood
      telomere length and telomere length from other cells that are more easily accessible has not
      been assessed. Therefore, this study will assess relations between blood telomere length from
      venous blood draw with telomere lengths from buccal cells, hair follicle cells, and blood
      cells from a finger prick. This study will assess whether a new measure of telomere damage
      (TIFS) is related to other measures of cell aging. This study will also assess the
      reliability of the venous blood draw telomere length across three different assays (PCR,
      southern blot, and fluorescent in situ hybridization or FISH). To meet these aims, this study
      will collect samples of these cells from 240 healthy volunteers from the community.
    

Detailed description: 
      Background and Significance: Briefly sketch the scientific background leading to the present
      proposal, critically evaluate existing knowledge (with references), and specifically identify
      the gaps the project is intended to fill. State concisely the importance and health relevance
      of the research described in this application by relating the specific aims to the broad,
      long-term objectives.

      Background and Rationale for Study:

      There is now a comprehensive amount of data linking physical health to telomere length.
      Because of this, telomere length is becoming a commercially available measure. Several
      companies offer or plan to offer this measure; Spectracell Laboratories (www.spectracell.com)
      is one example of such a company. In order to have one's own telomere length measured, it's
      as easy as putting a zip code into a search function on their website to find the
      geographically closest clinician that will order the test. It is thus important to consider
      that there are no studies that have examined the possible responses to learning one's
      telomere length, whether it might be helpful or not, or even harmful. Learning about one's
      telomere length may motivate healthy behaviors, such as exercise or smoking cessation. The
      likely possibility of people learning their telomere length diagnostically in the future, and
      the potential for both positive and negative effects of learning this information, provide a
      strong rationale for studying the psychological and behavioral effects of learning one's
      telomere length.

      Telomere length is a risk factor for disease:

      Telomere length has become a valuable risk factor, as it is now linked to and predictive of
      many diseases and early mortality. For example, being of below average TL in a healthy
      population predicts threefold risk of earlier mortality in two studies. This effect size is
      comparable to other well accepted risk factors. Telomere shortening in these cases is likely
      acquired from lifetime exposures (lifestyle, cigarette smoking, infections) as well as from
      some presumably smaller genetic influence.

      Telomeres can be very short from genetic/inherited conditions, and thus telomere testing can
      be helpful in the future to identify risk for rare genetically influenced conditions. Those
      with very short TL, probably in the bottom 5 to 10 percentile, are at risk of having a
      genetic defect in their genes that make telomerase (hTERT and hTR), and they may end up with
      haplosufficiency or half the normal dose of telomerase, which is not enough to protect
      telomeres from shortening. These defects are associated with short telomere syndromes,
      including liver fibrosis, lung fibrosis, bone marrow failure (aplastic anemia), poor immune
      function, and increased risk for cancers. Pulmonary Fibrosis (scarring of the lungs), a
      disease of aging which afflicts around 5 million people world wide, is characterized by short
      telomeres, and up to 15% of families with this condition have mutations in these genes for
      telomerase. Similarly, 3% of adults with aplastic anemia have telomerase mutations as well.
      If unrecognized and untreated, aplastic anemia quickly leads to death.

      In sum, given the role of telomere shortening in common diseases, the evidence that healthy
      lifestyle behaviors are associated with longer telomere length, and the clear role of very
      short telomeres in rare conditions, telomere testing can potentially provide benefit to
      individuals.

      Primary Aim 1: To assess whether learning one's personal blood telomere length (from immune
      cells) can have a positive impact on one's health behaviors and lifestyle factors (body
      weight, food choices, vitamin use, stress levels, and exercise). The investigators will
      further assess whether lifestyle and health behavior changes are related to subsequent
      changes in telomere length.

      Telomere length has become commercially available and may become widely available in the
      coming years. Telomere length is a new biomarker that may or may not be helpful to know. It
      is related to lifestyle factors. The investigators have found high perceived stress is
      related to shorter TL, which several other labs have replicated, and the investigators now
      find that exercise buffers this relationship. Specifically, those high stress individuals who
      do vigorous exercise do not show shorter telomeres. Telomeres can also lengthen over time, as
      evidenced by recent evidence and the investigators unpublished data. A study found that
      improvements in lifestyle (including nutrition, stress reduction, and weight loss) were
      associated with increases in telomerase, the enzyme that lengthens telomeres. The
      investigators' unpublished data also shows that those who show decreases in stress over one
      year have increases in telomere length during this period, with a correlation of r = -.44.
      The investigators thus expect that improvements in lifestyle and stress levels can lengthen
      or at least forestall shortening of telomeres, and with a sample size of 240, the
      investigators can test these associations.

      While the investigators are aiming to examine the behavioral and lifestyle effects of
      telomere length disclosure, of concern is whether receiving information about one's own blood
      telomere length could have a negative psychological impact. These concerns are quite valid,
      and a primary purpose of the present study, then, is to also examine the impact of finding
      out about one's blood telomere length on one's psychological well-being.

      The investigators draw from a relevant study in the field of Alzheimers. In a 2009 study,
      investigators randomized 162 adult children of parents with Alzheimer's disease (thus at high
      risk of Alzheimers) to either a disclosure group, where they learned whether or not they
      tested positive for ApoE allele, a susceptibility risk factor for Alzheimer's Disease, and a
      nondisclosure group, where they did not learn of their results (The REVEAL trial). They
      measured anxiety, depression, and test anxiety at three points over the next year. Among
      those in the disclosure group, those who tested positive showed slightly greater test-related
      distress than the negative group, but the difference was not clinically meaningful. The
      findings support the psychological safety of disclosing genetic risk factor data, at least in
      this specific case.

      More relevant to the investigators' current design was the REVEAL trial's primary outcome--
      whether there were significant differences between the disclosure group and the nondisclosure
      group in distress. Importantly, there were no significant differences in measures of distress
      between the disclosure and nondisclosure groups. Further, those who discovered they were
      APOE-negative experienced psychological relief, showing lower test related distress compared
      to those who received no information about their APOE-negative status at 6 months. These
      results suggest that individuals who discover a genetic vulnerability to a disease are no
      more likely to experience psychological distress, and that those who are at no considerable
      risk actually experience relief, it is important to examine such processes related to a
      marker like telomere length which has been linked to a wide array diseases and disorders.

      Learning about a risk factor like telomere length may or may not cause distress. The
      investigators' primary aim is to examine how being told one's own personal blood telomere
      length affects a person behaviorally and psychologically. The investigators expect it will
      cause only mild transient distress (slight increase on anxiety) if any, for those who are
      told they have short telomeres (bottom 25%). It is a susceptibility factor rather than a
      deterministic risk factor. In addition, learning about one's blood telomere length provides
      an opportunity for one to make behavior changes to improve blood telomere length, in contrast
      to a genetic risk factor that cannot change. Therefore, the investigators expect that people
      with short telomeres may be more motivated to increase healthy behaviors over the ensuing
      months. The investigators will emphasize that telomere length is changeable, and list the
      health behaviors that are associated with telomere length and thus may be linked to
      improvements in blood telomere length in a 'telomere information sheet.'

      Behavior may change merely as a result of learning about the importance of telomeres and how
      they can take measures to protect their telomeres (in the "telomere information sheet"),
      regardless of knowing one's personal results. Therefore, it is necessary to have a control
      group for this educational portion of the study. Therefore, the investigators randomize one
      group to learn their telomere length only at the end of the study so that they can serve as a
      'no result' control group for the study while the investigators assess behavior changes.

      In addition to assessing emotional response when they are informed of their personal results,
      in the experimental group, the investigators will also assess whether the volunteers have
      made any changes in their health behaviors and lifestyle at either a 3 Month Follow-Up or 9
      Month Follow-up from disclosure. The investigators will further examine, at 9 Month
      Follow-up, telomere length, by having participants return to the lab for a final blood draw.
      The investigators expect telomere length to change as a function of health behaviors and
      lifestyle changes that are undertaken and maintained throughout the 10 month period.
    

Intervention name(s): Telomere Disclosure Impact
Intervention type(s): Other
Intervention description(s): Participants were either provided or not provided information about their personal telomere length and how they compared to the rest of the sample.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Prevention