Association Between Informal Caregiving and Cellular Aging in the Survey of the Health of Wisconsin: The Role of Caregiving Characteristics, Stress, and Strain
Initially submitted September
Original Contribution Association Between Informal Caregiving and Cellular Aging in the Survey of the Health of Wisconsin: The Role of Caregiving Characteristics, Stress, and Strain
Whitney P. Witt
Ronald E. Gangnon
F. Javier Nieto
Corinne D. Engelman
Marsha R. Mailick
Halcyon G. Skinner
The pathophysiological consequences of caregiving have not been fully elucidated. We evaluated how caregiving, stress, and caregiver strain were associated with shorter relative telomere length (RTL), a marker of cellular aging. Caregivers (n = 240) and some noncaregivers (n = 98) in the 2008-2010 Survey of the Health of Wisconsin, comprising a representative sample of Wisconsin adults aged 21-74 years, reported their sociodemographic, health, and psychological characteristics. RTL was assayed from blood or saliva samples. Median T and S values were used to determine the telomere-to-single copy gene ratio (T/S) for each sample, and log(T/S) was used as the dependent variable in analyses. Multivariable generalized additive models showed that RTL did not differ between caregivers and noncaregivers (difference in log(T/S) = −0.03; P > 0.05), but moderate-to-high levels of stress versus low stress were associated with longer RTL (difference = 0.15; P = 0.04). Among caregivers, more hours per week of care, caring for a young person, and greater strain were associated with shorter RTL (P < 0.05). Caregivers with discordant levels of stress and strain (i.e., low perceived stress/high strain) compared with low stress/low strain had the shortest RTL (difference = −0.24; P = 0.02, Pinteraction = 0.13), corresponding to approximately 10-15 additional years of aging. Caregivers with these characteristics may be at increased risk for accelerated aging. Future work is necessary to better elucidate these relationships and develop interventions to improve the long-term health and well-being of caregivers. caregivers; caregiver strain; population-based studies; stress, psychological; Survey of the Health of Wisconsin Abbreviations: SHOW, Survey of the Health of Wisconsin; T/S, telomere-to-single copy gene ratio.
Informal caregiving (i.e., providing unpaid care to a family
member or friend with an illness or disability) is critical to the
care of the aging and disabled in the United States (
caregivers, however, are themselves at increased risk of poor
health outcomes (
). As the number of adults and
children requiring informal care rises (14), it is increasingly
important to understand the health implications for caregivers.
Telomere length, a putative biological marker of cellular
aging, may provide valuable information about the
pathophysiological consequences of caregiving. Telomeres are
DNA-protein complexes that cap the ends of chromosomes,
protecting them from degradation during cell division (
Telomeres generally shorten with age (
), and short
telomere length has been associated with numerous health
) and earlier mortality (
although evidence is conflicting (
). Short telomere
length may be indicative of a poor biological state or higher
disease risk (35).
Previous work has provided conflicting evidence for an
association between caregiving and shortened telomere length
). However, perceived stress has consistently been
associated with shorter telomeres or reduced telomere
). Stress theory and recent research suggest
that the environment may play a critical role in explaining
why some caregivers, but not others, experience elevated
stress or adverse health outcomes (50). The details of a
caregiver’s role and experiences may be important environmental
factors that might influence these outcomes and can be
readily monitored in the clinical setting. However, aside from
1 study examining duration of caregiving (
associations among caregiving characteristics, caregiver strain, and
telomere length have yet to be examined. Elucidating these
relationships will improve our understanding of the
physiological impact of caregiving and help identify high-risk
caregivers and potential points of intervention for improving
In this study, we sought to determine the association
between caregiving and telomere length in a population-based
sample. Specifically, we aimed to determine whether and to
what extent 1) caregivers had shorter telomeres than
noncaregivers, 2) global perceived stress in the past year was
associated with telomere length, and 3) caregiving characteristics
and caregiver strain were associated with telomere length. We
further evaluated whether this association differed by level of
global stress. Findings from this study should help to clarify
the pathophysiological impact of caregiving, improving our
ability to identify, monitor, and track high-risk caregivers.
Further, the findings will suggest points of intervention to
prevent or ameliorate the adverse consequences of
caregiving, potentially improving the long-term health of both
caregivers and their families.
Data were from the 2008–2010 Survey of the Health of
Wisconsin (SHOW). The SHOW is an annual statewide
survey of civilian noninstitutionalized adults aged 21–74 years,
representative of the state of Wisconsin. A description of
SHOW procedures is available elsewhere (
participants were selected from a random sample of Wisconsin
households using a 2-stage cluster sampling approach.
Participants completed face-to-face interviews, self-administered
questionnaires, and a physical examination and provided a
blood (venipuncture) or saliva (Oragene; DNA Genotek
Inc., Kanata, Ontario, Canada (www.dnagenotek.com))
sample. All informal caregivers who provided samples (n = 240)
were included in the present study. We randomly selected a
subset of noncaregivers with samples (n = 98),
frequencymatched to the caregivers on age and sex. This study was
approved by the Health Sciences Institutional Review Board of
the University of Wisconsin-Madison.
Independent variables. Identification of caregivers.
Informal caregivers were identified by the following question:
“There are situations in which people provide regular unpaid
care or assistance to a family member (including children) or
a friend who has a long-term illness or a disability. In the past
12 months, did you provide any such care or assistance to a
family member or friend living with you or living
Global stress. The Global Perceived Stress Scale from
the Jackson Heart Study (
) was used to measure global
stress over the last 12 months. This scale assesses perceptions
of ongoing stressful conditions in 8 domains (i.e., job,
relationships, neighborhood, caring for others, legal problems,
medical problems, racism/discrimination, and meeting basic
needs). Participants rated each domain on a 4-point Likert
scale (ranging from not stressful (0) to very stressful (
and scores for the items were summed ( possible range, 0–24).
Higher scores indicated greater stress.
Caregiving characteristics. Caregivers reported their
duration of caregiving (years); number of hours of care provided
per week; travel distance from the care recipient (co-resident,
≤20 minutes away, or >20 minutes away); relationship to the
care recipient (spouse, adult child (caring for a parent), parent
(caring for a child), or other friend/relative); the care
recipient’s condition (dementia, recovery from surgery, injury,
acute illness, or other condition), age, and sex; number of
care recipients in the past year; and whether they were
currently providing care.
Caregiver strain. A 12-item version of the Caregiver
Strain Index (
) was used to evaluate perceived strain
among caregivers. This version of the index asked
respondents whether 12 statements related to caregiving applied
to them (e.g., “It is inconvenient for you”). The number of
items endorsed was summed ( possible range, 0–12). Higher
scores indicated greater strain. Cronbach’s α was 0.81.
Dependent variable: telomere length. Telomere length
assays were conducted using stored DNA extracted from
blood using phenol/chloroform (
) or from saliva (n = 45;
32 caregivers (13.3%) and 13 noncaregivers (13.3%)) using
the DNA Genotek protocol (www.dnagenotek.com).
Relative telomere length was assayed using quantitative real-time
polymerase chain reaction (
). This assay uses separate
primer pairs to hybridize and amplify 1) telomere hexamer
repeats and 2) single-copy gene (β2-globin) DNA. All
polymerase chain reactions were performed on the Applied
Biosystems 7900HT Fast Real-Time PCR System (Applied
Biosystems, Inc., Foster City, California). The data were
then analyzed with Applied Biosystems SDS software
(Applied Biosystems, Inc.) to generate the standard curve for
each plate. The intraassay coefficients of variation of the
threshold cycle values for the telomere and single-gene
reactions were 1.27% and 1.41%, respectively. The interplate
variations were 4.79% and 4.06%, respectively. All samples
were analyzed in triplicate. The median T value and the
median S value were used to determine the telomere-to-single
copy gene ratio (T/S) for each sample, and the natural
logarithm of the ratio, log(T/S), was used in the analyses to
account for skewness. A linear transformation of the T/S ratio
was used to estimate telomere length in base pairs: base pairs =
(T/S) × 1,470.8 + 7,674.5, based on comparisons between
telomere restriction fragment lengths, as determined by Southern
blot, and T/S ratios among samples previously examined by
the laboratory (n = 16; r = 0.57, P = 0.02).
Covariates. Sociodemographic characteristics.
Participants reported their age, sex, race/ethnicity (non-Hispanic
white vs. other), annual income, educational attainment,
employment status (employed in the past week vs. unemployed),
type of health insurance (none, public, private, or mixed),
marital status (married/partnered,
divorced/widowed/separated, or never married), and the number of adults and
children in the household. Participants reported their combined
annual family income categorically (e.g., $25,000–$29,999).
These data were recoded to the midpoint to approximate a
continuous measure; the highest category (≥$200,000) was
recoded to $392,396 by assuming a Pareto distribution of
). Educational attainment was reported as the
highest grade or level of schooling completed and was recoded as
years of education.
Lifestyle factors. Information on smoking (current,
former, or never smoker), alcohol consumption (nondrinker,
moderate drinker, or risky drinker), leisure-time and
transportation-related physical activity (metabolic equivalent
of task (MET)-minutes per week), and diet ( fruit/vegetable
consumption and percentage of calories derived from fat
)) was obtained via personal interview. Sleep quality
(single-item report on a 5-point Likert scale; dichotomized
to excellent/very good/good vs. fair/poor), sleep problems,
and nightly sleep duration (hours; continuous nonlinear term)
were reported using the self-administered questionnaires.
Health factors. Respondents reported their history of 47
health conditions (see the Web Appendix, available at http://
aje.oxfordjournals.org/), and the number of health conditions
was calculated. An inventory of prescription medications
taken by the participant was conducted during the home
interview using a standardized protocol (
), and the total
number of prescription medications used in the past 30 days
was calculated. Height and weight were measured during the
examination visit, and body mass index (weight (kg)/height
(m)2) was calculated.
Analytical approach. All analyses were conducted in R
). Multiple imputation with predictive mean
matching was used to predict the values of missing data (
imputations were conducted. Nonlinear transformations were
allowed when predicting missing values for continuous
variables. All analyses were conducted using the imputed data
sets. Estimates and standard errors were combined using
Rubin’s rules (
Caregiver and noncaregiver characteristics were compared
using cross-tabulations with χ2 tests, t tests, or Wilcoxon
tests. All tests of statistical significance were 2-sided.
Generalized additive models with thin-plate regression splines were
constructed to examine whether 1) caregivers had shorter
telomeres than noncaregivers, 2) global stress was associated
with shorter telomere length, and 3) caregiving
characteristics and caregiver strain were associated with telomere length.
Multivariable analyses controlled a priori for caregiver age,
sex, race, number of chronic conditions, and prescription
medication use. Manual backward selection was used to
determine whether additional sociodemographic characteristics
were included in the model: All covariates were included
simultaneously, and each variable with P < 0.20 was removed
individually. If removing the variable did not substantially
change the β coefficient of the primary independent variable
(>10%), it was not included in the final model. The models
were also tested while controlling for lifestyle factors that
may lie in the pathway between caregiving or stress and
telomere length—including diet, exercise, smoking, alcohol
consumption, and sleep—and body mass index. Because these
factors did not substantively influence the findings, only
the results from the parsimonious models are reported. All
continuous variables were tested as nonlinear terms in the
models; generalized cross-validation (
) was used.
Follow-up analyses were conducted among caregivers in
order to determine whether the association of global stress
and telomere length differed by the amount of reported caregiver
strain. The variables were dichotomized at the median value
among caregivers (global stress: 6; strain: 4), and mutually
exclusive groups were created. The association between these
stress-strain groups and telomere length was evaluated as above.
In order to account for the complex survey design, we then
conducted these analyses using sampling weights. Nonlinear
terms were included in the models as natural cubic splines,
with fixed degrees of freedom estimated from the generalized
In addition, because mean telomere length differed by
tissue source (blood: mean T/S = 0.91; saliva: mean T/S = 1.16
(P < 0.05)), we performed a sensitivity analysis dropping the
Table 1 gives the characteristics of caregivers and
noncaregivers in this study. Caregivers did not differ significantly
from noncaregivers with regard to any of the characteristics.
In the unadjusted analyses (Table 2), there was no mean
difference in telomere length between caregivers and
noncaregivers (difference = −0.07; P = 0.33). Global stress was
nonlinearly associated with telomere length, such that persons
reporting moderate global stress (approximately 7–11 points
on the global stress scale; data not shown) had longer
telomeres. When stress was examined categorically, persons
with stress scores of 7–11 had significantly longer telomeres
than those with stress scores of 6 or less (difference = 0.14;
P = 0.04). Among caregivers, providing more hours of care
per week and reporting greater strain were associated with
shorter telomeres (difference in log(T/S) per doubling of
hours = −0.04 (P = 0.04); difference in log(T/S) per doubling
of strain = −0.06 (P = 0.05)).
Caregiver status. In the adjusted analyses, there was no
mean difference in telomere length between caregivers and
noncaregivers after controlling for covariates (difference =
−0.03; P = 0.64 (Table 3)). As expected, older age was
associated with shorter telomeres (P = 0.004; Figure 1).
Global stress. Perceived global stress was significantly
nonlinearly associated with telomere length: Persons
reporting moderate global stress (about 7–11 points on the Global
Perceived Stress Scale) had longer telomeres (P = 0.01;
Figure 2). When this variable was examined categorically,
persons with stress scores of 7–11 had significantly longer
telomeres than those with scores of 6 or less (difference =
0.15 (about 184 base pairs); P = 0.04 (Table 4)).
Caregiving characteristics. Among caregivers, those
who provided more hours of care per week had significantly
shorter telomeres (difference in log(T/S) per doubling of
hours = −0.04 (about 54 fewer base pairs); P = 0.004) (see
Table 5, bivariate-adjusted results). In addition, those
providing care to persons under the age of 25 years had
significantly shorter telomeres than those caring for older persons,
equating to as much as a 342-base-pair difference. Finally,
greater caregiver strain was associated with shorter
telomeres (difference in log(T/S) per doubling of strain = −0.07
(about 99 fewer base pairs); P = 0.03). When all of the
caregiving characteristics were included in the model
simultaneously (see Table 5, multivariate-adjusted results),
these findings remained. In addition, persons who did not
co-reside with the care recipient had shorter telomeres
than those who did. Full regression results are shown in
Web Tables 1–7.
In addition, the association between caregiver strain and
telomere length differed by the level of stress reported by
caregivers. As Figure 3 shows, persons who reported high
caregiver strain but low global perceived stress had
significantly shorter telomeres than those reporting both low strain
and low stress (about 316 fewer base pairs; P = 0.02) and
borderline significantly shorter telomeres than those with high
strain and high stress (about 250 fewer base pairs; P = 0.08)
or low strain and high stress (about 302 fewer base pairs; P =
0.05). The overall interaction did not reach statistical
significance (overall P = 0.13).
When saliva samples were dropped from the analyses, the
results were largely unchanged. However, the association
−0.14 −0.26, −0.01
Abbreviations: CI, confidence interval; T/S, telomere-to-single copy
a The model also controlled for age as a nonlinear term (P < 0.01).
b For continuous covariates, the estimate represents the change in
log(T/S) per unit increase in the covariate; for categorical covariates,
the estimate represents the difference from the reference group.
between moderate-to-high stress and telomere length was
attenuated slightly (difference = 0.13; P = 0.11 (data not
shown)). In addition, the estimate for caring for a person
under 25 years of age was attenuated (difference = −0.16;
P = 0.11), and the association between strain and telomere
length was of borderline significance (difference = −0.09;
P = 0.07).
To our knowledge, this was the first population-based
study to examine the association between caregiving and
telomere length. The findings from this study highlight
subgroups of caregivers who have shorter telomeres (i.e., those
providing more hours of care, caring for a child or young
adult, or reporting greater strain) and may therefore be at
particularly high risk of poor health outcomes. Further, the
findings suggest that stress and caregiver strain have complex,
nonlinear associations with cellular aging that are in need
of further examination.
Previous studies of the association between caregiving and
telomere length have been conducted in small convenience
samples, and results have been conflicting (
present study provides evidence against overall differences in
telomere length by caregiver status. This null result may be
Abbreviations: CI, confidence interval; T/S, telomere-to-single copy
a For continuous covariates, the estimate represents the change in
log(T/S) per unit increase in the covariate; for categorical covariates,
the estimate represents the difference in log(T/S) from the reference
b Global stress over the last 12 months was self-reported using the
Global Perceived Stress Scale from the Jackson Heart Study (
Eight items were measured on a 4-point Likert scale (ranging from
not stressful (0) to very stressful (
)), and scores were summed
(possible range, 0–24); higher scores indicate greater stress.
attributable to caregiver heterogeneity (
subgroup sizes limited our ability to examine this, future
work should more closely examine the role of heterogeneity
in telomere attrition among caregivers.
While several previous studies have provided evidence that
greater psychological stress is associated with shorter
), we found that participants who reported
a moderate-to-high level of global stress in the past year had
longer telomeres than those with low levels of stress. It is
possible that our population-based sample captured a broader
swath of the stress distribution than previous
conveniencebased studies, which may have identified only the
associations at the higher end of the stress distribution. In addition,
it is possible that psychological stress over short,
intermediate, and long terms has differential associations with cellular
). Interestingly, the “U-shaped” curve observed
in this study is reminiscent of the association between stress
and other factors, such as resiliency (75) and physiological and
mental function (
): While a large amount of stress is
deleterious, a small amount may improve fitness. Future work is
clearly needed to confirm and further explore this finding.
In the only previous study to have examined the
association between caregiving characteristics and telomere length,
Epel et al. (
) reported that longer duration of care was
associated with shorter telomeres. While we found no evidence
of this association in our sample, we did find that more hours
per week of caregiving, younger age of the care recipient, and
greater caregiver strain were associated with shorter
telomeres. Psychological aspects, such as feeling more
uncertainty or less choice (
) or perceiving a higher level of
care recipient disability/need (79), may contribute to poor
health outcomes. Interestingly, the association between
number of hours per week of providing care and shorter telomere
length was not attributable to caregivers’ time use (e.g.,
reduced time spent exercising or sleeping) and was also
independent of stress, strain, health factors, and caregivers’ health
behaviors (data not shown).
Caregivers of persons under the age of 25 years also had
significantly shorter telomeres than caregivers of older
persons (although this effect was attenuated when saliva samples
were dropped). Providing care for a child who is ill or
disabled may be considered “off-time” or nonnormative (
and has been associated with feelings of uncertainty and
), and may therefore be more deleterious to
the caregiver. These changes may accumulate over time
and may not manifest as health problems until later in life
(71), plausibly due to accelerated telomere attrition.
To our knowledge, this is the first study to have found that
greater caregiver strain is associated with shorter telomeres. In
addition, we found that persons who had high levels of strain
but low levels of stress had substantially shorter telomeres than
other caregivers, translating to an estimated 7–10 additional
years of aging (
17, 24, 83
). Some caregivers may have
underreported their level of perceived global stress (
because of their engagement in the caregiver role (i.e., being
strong for the family), stress habituation, or avoidant coping
or denial, which is deleterious over the long term (
Additionally, the associations between global stress and strain
with telomere length may differ, as different types of adversity
are associated with different biological cascades (
Further, experiencing stress outside of the caregiving realm may
indicate greater connection with the community and
engagement outside of caregiving, which may be protective (
). However, because the overall interaction was not
statistically significant, future work with greater statistical power will
be necessary to confirm and clarify these findings.
Several potential biological mechanisms also exist that
may explain the observed association between greater global
stress and longer telomeres and the potential discordance in
telomere length by levels of strain and global stress, including
telomerase activation, alternative lengthening of telomeres,
and changes in the leukocyte subpopulation (
Psychological stress contributes to a biological cascade
resulting in increased cellular stressors (e.g., oxidative stress)
that may trigger telomerase activation (104) or alternative
lengthening mechanisms. Indeed, some studies have found
an association between stress or adverse exposures such as
caregiving and increased telomerase activation (
), which could contribute to telomere lengthening.
Finally, telomere length and dynamics differ across different
types of white blood cells (
), and observed lengthening of
telomeres may be due to changes in the cell mixture (
). Therefore, if caregiving, stress, or strain contributed
to different cell-type proportions, this might contribute to
observed telomeric differences.
This study has several important implications. The
telomere length differences in our study were in line with the
magnitudes seen in relation to chronic disease burden (about
132 base pairs) (
) and myocardial infarction (about
300 base pairs) (
), highlighting the potential clinical
significance of these findings. Assessing and monitoring hours
per week of caregiving, age of the care recipient, and level of
caregiver strain may help clinicians identify high-risk
caregivers. Second, interventions that reduce psychological
distress have been shown to increase telomere length (
), and those that reduce caregiver strain or hours per
week of providing care, such as coping-skills training or
respite care, should be tested for their impact on cellular aging
among caregivers. Self-care behaviors, such as exercise, may
also help to prevent telomere attrition and subsequent poor
health outcomes. Finally, this study highlights the need for
additional research to better understand the role of both
caregiving characteristics and stress in telomere dynamics. The
potential interaction between caregiver strain and stress in
the relationship with telomere length should also be
examined further, in order to better understand how these factors
may adversely influence caregivers over time.
This study had potential limitations. The use of telomere
length as a biomarker of aging, chronic disease, or mortality
risk remains controversial. Studies examining the
associations between telomere length and mortality have produced
mixed results, and telomere length does not meet all of the
criteria for a biomarker of aging (
41, 111, 112
recent meta-analyses have provided evidence supporting
associations for at least some disease outcomes (
telomere length was assessed at a single time point, and we
could not control for innate individual variation in telomere
length. Similarly, we could not evaluate the impact of
longitudinal changes in stress or strain on telomere length. Third,
our sample size did not permit us to examine heterogeneity
in the association between caregiving and telomere length.
Fourth, telomere length features that may be important, such
as the relative sizes of cell subpopulations (
) or the
shortest telomeres in the sample (117), were not examined in
this study. Differences in cell-type mixtures may be a source
of residual confounding. Finally, the biological samples in
this study consisted of both blood and saliva samples. When
the saliva samples were excluded, some results were
attenuated. Our results should be interpreted in light of the
sensitivity analysis, and future work will be needed to replicate and
confirm our findings.
This study also had several important strengths. The
sample was selected from participants in a large population-based
study, improving generalizability. We assessed several
caregiving factors and both global stress and caregiver strain.
Finally, we were able to measure and test numerous covariates
in the models, including health behaviors, body mass index,
and sociodemographic factors, that may have confounded the
associations of interest.
In conclusion, this population-based study provided
evidence that caregiving factors, including hours per week of
care, caring for a young person, and greater caregiver strain,
were associated with shorter telomere length, a marker of
accelerated cellular aging. Further, moderate-to-high stress was
associated with longer telomeres. The findings suggest that
stress and caregiving situations have adverse consequences
on a physiological level that may be predictive of future
health problems. Future work is necessary to better elucidate
these relationships and to develop interventions that will
buffer telomere attrition and improve the long-term health
and well-being of caregivers and their families.
Author affiliations: Department of Population Health
Sciences, School of Medicine and Public Health, University of
Wisconsin-Madison, Madison, Wisconsin (Kristin Litzelman,
Whitney P. Witt, Ronald E. Gangnon, F. Javier Nieto, Corinne
D. Engelman, Halcyon G. Skinner); Department of
Biostatistics and Medical Informatics, School of Medicine and Public
Health, University of Wisconsin-Madison, Madison, Wisconsin
(Ronald E. Gangnon); School of Social Work, University of
Wisconsin-Madison, Madison, Wisconsin (Marsha R. Mailick);
and Waisman Center, University of Wisconsin-Madison,
Madison, Wisconsin (Marsha R. Mailick).
Dr. F. Javier Nieto is the director of the Survey of the
Health of Wisconsin (SHOW), and Dr. Corinne D. Engelman
is a SHOW investigator. All authors contributed to this work
Funding for SHOW was provided by the Wisconsin
Partnership Program (grant 233 PRJ56RV), the National
Institutes of Health (Clinical and Translational Science Award
5UL 1RR025011), and the National Heart, Lung, and
Blood Institute (grant 1 RC2 HL101468). Funding for this
study was provided by a training grant from the National
Institute on Aging (grant F31 AG 044073; Principal
Investigator: Kristin Litzelman) and the Center for Demography of
Health and Aging at the University of Wisconsin-Madison,
which supported the caregiving component of the SHOW
interviews (Principal Investigator: Whitney P. Witt). The assays
of telomere length were supported by National Institutes of
Health grant RO-1 CA132718.
We thank Dr. Lisa A. Boardman and Ruth A. Johnson for
their assistance in completing the telomere length assays.
Conflict of interest: none declared.
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