Nonuniform, age-related decrements in regional sweating and skin blood flow
Caroline J. Smith, Lacy M. Alexander, and W. Larry Kenney
Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania
Submitted 11 June 2013; accepted in final form 6 August 2013
Smith CJ, Alexander LM, Kenney WL. Nonuniform, age-related
decrements in regional sweating and skin blood flow. Am J Physiol
Regul Integr Comp Physiol 305: R877–R885, 2013. First published
August 7, 2013; doi:10.1152/ajpregu.00290.2013.—Aging is associ-
ated with attenuated thermoregulatory function that varies regionally
over the body. Decrements in vasodilation and sweating are well
documented with age, yet limited data are available concerning the
regional relation between these responses. We aimed to examine
age-related alterations in the relation between regional sweating
(RSR) and skin blood flow (SkBF) to thermal and pharmacological
stimuli. Four microdialysis fibers were inserted in the ventral forearm,
abdomen, thigh, and lower back of eight healthy aged subjects (64 ?
7 yr) and nine young (23 ? 3 yr) during 1) ACh dose response (1 ?
10?7to 0.1 M, mean skin temperature 34°C) and 2) passive whole
body heating to ?1°C rise in oral temperature (Tor). RSR and SkBF
were measured over each microdialysis membrane using ventilated
capsules and laser-Doppler flowmetry. Maximal SkBF was measured
at the end of both protocols (50 mM SNP). Regional sweating
thresholds and RSR were attenuated in aged vs. young at all sites (P ?
0.0001) during whole body heating. Vasodilation thresholds were
similar between groups (P ? 0.05). Attenuated SkBF were observed
at the arm and back in the aged, representing 56 and 82% of those in
the young at these sites, respectively (0.5 ?Tor). During ACh perfu-
sion, SkBF (P ? 0.137) and RSR were similar between groups (P ?
0.326). Together these findings suggest regional age-related decre-
ments in heat-activated sweat gland function but not cholinergic
sensitivity. Functional consequences of such thermoregulatory impair-
ment include the compromised ability of older individuals to defend
core temperature during heat exposure and a subsequently greater
susceptibility to heat-related illness and injury.
sweating; aging; laser-Doppler flowmetry; skin blood flow; sweating
HUMAN AGING IS ASSOCIATED with altered thermoregulatory func-
tion during both passive and exercise-induced hyperthermia,
including attenuated reflex cutaneous vasodilation (26) and
eccrine sweating responses (3, 18, 24). A functional loss of
active cholinergic vasodilation cotransmitter function and dys-
function of second-messenger pathways (i.e., nitric oxide bio-
availability) (8, 11, 12, 31) contribute to attenuated cutaneous
vasodilatory responses to elevations in core temperature
(Tcore), hindering convective heat loss. An age-related decline
in thermoregulatory sweating further compromises heat loss
and increases thermal strain in warm ambient conditions and
during exercise. Reduced evaporative heat loss from the skin
surface results from a decline in thermoregulatory sweating,
due to a decreased thermal sensitivity (32) and atrophy of the
sweat glands (17, 19), producing a lower sweat output per
gland (23, 24, 39).
Regional variation in sweating and skin blood flow (SkBF)
responses to passive heating are well documented (29); how-
ever, limited data are available concerning the relation between
these responses and how they may vary with aging (19, 20). It
has been suggested that an age-related decline in reflex cuta-
neous vasodilation precedes decrements in sweat gland func-
tion (15, 19), with the latter resulting from an initial reduction
in sweat gland output followed by a subsequent decline in the
number of heat-activated sweat glands (HASG) (15). Physio-
logical mechanisms contributing to the disproportionate tem-
poral progression of sudomotor and vasomotor dysfunction
with age remain unclear. Furthermore, despite attempts to
identify a putative signaling pathway or cotransmitter relating
the two responses, including speculation over VIP (40), bra-
dykinin (4), and nitric oxide (33), a single mechanism has not
yet been elucidated. The regional progression of age-related
vasomotor and sudomotor dysfunction is not well character-
ized, with limited vasomotor data available and conflicting
results of regional sudomotor adjustments. Several studies
have indicated a peripheral-to-core (torso) progression in sweat
gland dysfunction with aging (20), whereas others have re-
ported a sequential progression from lower to upper body
regions (19). In contrast to these data, a gap in knowledge
exists regarding regional variation in SkBF in an aged popu-
lation. Although age-related decrements in sweating and SkBF
are widely recognized, a thorough examination of regional
differences in an aged population is largely lacking, with
changes in distribution subsequently less well understood.
Furthermore, most studies investigating sudomotor and vaso-
motor adjustments with age have not matched subject groups
for anthropometric parameters and/or aerobic capacity (15),
confounding separation of these influences from aging effects
per se. Understanding such age-related thermoregulatory dys-
function is particularly important in the current aging popula-
tion, who are particularly susceptible to heat-related illness and
injury both during passive heat stress and during physical
activity in the heat.
The present study aimed to examine age-related decrements
in the relation between regional sweating and SkBF during
whole body passive heating using subject groups matched for
anthropometric characteristics and V˙O2max. Based on previous
regional sweating rate (RSR) data and the putative relation
between RSR and SkBF, we hypothesized that regional, age-
related decrements in sweating and SkBF would occur in a
nonuniform manner over the body, indicating a peripheral-to-
central (torso) progression. Considering decrements in SkBF
have been observed in advance of RSR, we further hypothe-
sized that attenuated SkBF responses would be greater than
decrements in RSR.
Experimental protocols were approved by the Institutional Review
Board at The Pennsylvania State University and conformed to the
guidelines set forth by the Declaration of Helsinki. Verbal and written
consent were voluntarily obtained from all subjects before participa-
Address for reprint requests and other correspondence: C. J. Smith, 228 Noll
Laboratory, Univ. Park, PA 16802 (e-mail: firstname.lastname@example.org).
Am J Physiol Regul Integr Comp Physiol 305: R877–R885, 2013.
First published August 7, 2013; doi:10.1152/ajpregu.00290.2013.
0363-6119/13 Copyright © 2013 the American Physiological Society http://www.ajpregu.orgR877
tion. Nine healthy aged men and women (64 ? 2 yr, 4 men and 5
women) participated in the study and were compared with nine young
men and women (23 ? 2 yr, 5 men and 4 women) from a previous
study following the same experimental protocol (37). Subjects under-
went a complete medical screening, including blood chemistry, com-
plete lipid, renal, and liver enzyme profile evaluation (Quest Diag-
nostics Nichol Institute, Chantilly, VA), resting electrocardiogram,
and physical examination. All subjects were screened for the presence
of cardiovascular, dermatological, and neurological disease. Subjects
were nonsmokers, nondiabetic, normally active (neither sedentary nor
highly exercise trained), and were not taking medications, including
antihypertensives or other drugs that may affect the cardiovascular
system, including antioxidants, hormone replacement therapy, or oral
contraceptives. All young women were normally menstruating and
were tested during the early follicular phase (days 1–7) of their
menstrual cycle. All subjects completed a graded exercise test (Bruce
protocol) on a semirecumbent bike to determine V˙O2peak in a room
maintained at 23°C, 40% relative humidity. Subjects underwent a dual
x-ray absorptiometry scan for assessment of regional body composi-
All subjects completed the following two experimental protocols:
1) whole body heating and 2) ACh dose response, of which the order
was randomized between subjects. Experiments were conducted on
different days separated by a minimum of 1 wk to allow full healing
of microdialysis insertion sites and ensure recovery from whole body
heating. Protocols were performed in a thermoneutral laboratory with
the subjects in a supine position. Four intradermal microdialysis fibers
(MD 2000; Bioanalytical Systems) (10 mm, 20-kDa cutoff mem-
brane) were inserted as previously described (9) in the ventral fore-
arm, abdomen, thigh, and lower back. Foam was placed underneath
the subject to prevent pressure being placed on the equipment and the
measurement site at the lower back. Fibers were inserted following
temporary anesthesia of each site using ethyl chloride spray (Gebauer,
Cleveland, OH) (14). Ethyl chloride spray was selected because of its
short period of anesthesia, ease of application to the MD fiber
insertion sites, and showing no effect on SkBF during or after
hyperemia, compared with using ice (pilot data from our laboratory,
unpublished observation). Sites were selected based on high and low
sweat regions from whole body sweat maps and using similar ana-
tomical measurements to determine MD fiber placement (35, 36).
Briefly, the abdomen site was identified on the left side of the body as
midway between the anterior superior iliac spine and the navel; the
thigh site was calculated as 0.6? the upper leg length (distance from
anterior superior iliac spine to the proximal edge of the patella); the
lower back site was identified on the left side of the body at the height
of the anterior superior iliac spine, 5–10 cm lateral to the vertebrae.
Initial insertion trauma was allowed to subside for 60–90 min, during
which time lactated Ringer solution was perfused through all fibers at
a rate of 2 ?l/min (Bioanylitical Systems Bee hive and Baby Bee
microinfusion pumps, West Lafayette, IN).
Whole body heating was achieved using a water-perfused suit that
covered the entire body with exception to the head, hands, and feet.
Local skin temperature (Tsk) was continuously measured at six sites
using copper-constantan thermocouples (calf, thigh, abdomen, chest,
upper arm, and upper back), and an unweighted mean skin tempera-
ture (Tsk mean) was calculated. Oral temperature (Tor) was measured as
an index of body Tcore using a thermistor placed in the sublingual
sulcus throughout baseline and whole body heating. Following veri-
fication of appropriate placement against temperature readings, the
thermistor was taped in place, and subjects were instructed to maintain
a closed mouth for the duration of the protocol. Tor was closely
monitored throughout heating. Mean body temperature (Tbody) was
calculated as Tbody? (0.9 ? Tor) ? (0.1 ? mean Tsk) (5). An index
of SkBF was measured using laser-Doppler flowmetry probes (Moor-
LAB; Moor Instruments) placed over each microdialysis site measur-
ing cutaneous red blood cell flux, which was recorded continuously
during the experiment. Arterial blood pressure was measured via
brachial auscultation every 5 min following resolution of hyperemia
induced by MD fiber insertion. Mean arterial pressure (MAP) was
calculated as 1/3 systolic blood pressure ? 2/3 diastolic blood pres-
sure. SkBF was expressed as cutaneous vascular conductance (CVC;
red blood cell flux/MAP) and normalized as percent of maximal CVC
Total body sweating rate was determined from the change in body
mass during whole body hearting using a scale accurate to ?10 g
(SECA. model 770 1321143). Values were not corrected for meta-
bolic and respiratory losses. Local sweating rates were measured
using ventilated capsules with compressed medical-grade nitrogen
used as the perfusion gas (28, 34), specifically manufactured so that
sweating rate and laser-Doppler flux could be measured simultane-
ously. Sweat capsules (4.46 cm2) were positioned over the center of
the membrane portion of each microdialysis fiber. The temperature
and humidity of the air flowing out of the capsules were measured
using capacitance hygrometers that were calibrated by the manufac-
turer and regularly calibrated using reference solutions of known
temperature and humidity (model HMT330; Vaisala, Helsinki, Fin-
land). The sensitivity of the system was assessed by injecting set
volumes of distilled water (5–20 ?l) in the capsules, and the area
under the curve was calculated (unpublished pilot data). Sweating rate
(SR) was calculated based on the change in relative humidity of the air
as it passed through the capsule (?rh) at a determined air flow (AF),
the density of saturated steam at the given temperature (D), and the
capsules surface area (SA), using the following equation (28):
SR??AF???rh⁄ 100?? D?⁄ SA.
Whole body heating. Upon arrival to the laboratory, subjects
provided a urine sample for assessment of hydration status via urine
specific gravity and osmolality, and body mass was recorded. Follow-
ing MD fiber insertion and resolution of insertion trauma, baseline
data were collected for 20 min with mean Tskmaintained at thermo-
neutral using a water-perfused suit (34°C). After collection of baseline
data, 50°C water was perfused through the suit to elevate Torby 1°C,
after which Torwas clamped for 5 min by reducing the temperature of
the water perfusing the suit. After 5 min of steady-state laser-Doppler
flux values, water perfusing the suit was returned to 34°C and 50 mM
SNP (Nitropress; Abott Laboratories, Chicago, IL) was perfused for
20 min through each MD site at a rate of 4 ?l/min to obtain maximal
ACh dose response. Following MD fiber insertion and resolution of
insertion trauma, baseline data were collected for 20 min. Immedi-
ately after baseline measurement, Tsk was clamped at 34°C (water-
perfused suit) during perfusion of seven ascending concentrations of
ACh at a rate of 2 ?l/min for 10 min each: 1 ? 10?7to 1 ? 10?1M
dissolved in Ringer solution in 10-fold increments. This amount of
time allowed for a plateau in SkBF at each concentration of ACh.
After completion of the ACh dose response, 50 mM SNP was
perfused through all sites at a rate of 4 ?l/min to induce maximal
cutaneous vasodilation (LDF) (13, 22).
Data and Statistical Analysis
Data were digitalized at 40 Hz, recorded, and stored for offline
analysis using Windaq software and the Dataq data acquisition system
(Windaq; Dataq Instruments, Akron, OH). Baseline values were
determined as the last 5 min before commencing whole body heating.
Local sweating and SkBF data are presented as mean values over 60
s at each 0.1°C rise in Tor throughout the duration of the heating
protocol. Maximal SkBF values were averaged over a stable 60-s
plateau during perfusion of 50 mM SNP. Sweating and cutaneous
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