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Age-Related Changes of the Cutaneous Microcirculation in vivo
Abstract
The architectural frameworks of the skin microcirculation are rather complex and change continuously with aging. But these changes are yet poorly documented in vivo.
Using non-invasive methods belonging to the field of biometrology, the study aimed to investigate quantitatively the changes of the cutaneous microvasculature in different anatomic sites with age.
Measurements were performed on crow's feet, forehead, volar forearm and dorsum of hand in 50 women (aged 20-74 years who consisted of 10 probands in each live decades). The superficial vascular plexus was scanned by videocapillaroscopy and assessed with the software Capilab Toolbox. The subpapillary vascular plexus was explored with laser Doppler flowmetry. The skin color a* was analyzed by chromametry.
A marked site and age effect on the skin microcirculation has been demonstrated. The density of capillary loops in the eldest group decreased by about 40-70% compared with the youngest group whereas the vascular length increased by 35-156%. The capillary density in the back of the hand was 4 times higher than in the crow's feet. The vascular length in the crow's feet was 3 times longer than in the back of the hand. Both blood flow and skin redness (a*) increased also with age.
Both morphology and quantification of the cutaneous microvasculature showed changes with site and age. Videocapillaroscopy associated to an image processing and laser Doppler flowmetry revealed different vascular layers. So the combination of both instruments offers an easy way to observe the architectural frameworks in vivo.
... In young subjects, the median (95 % CI) baseline BPU values were 35 (29, 46), 38 (29, 41) before continuous NIR exposure and placebo, and 38 and 41 (37, 46) before intermittent NIR exposure and placebo, respectively. In middle-aged subjects, the median (95 % CI) baseline BPU values were 34 (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) and 44 (37, 48) for intermittent NIR exposure and placebo, respectively. We observed a considerable inter-individual variation in local skin blood flow response to all NIR PBM interventions. ...
... Higher median percentage changes in blood flow in middle-aged subjects than young subjects under the same intermittent NIR exposure duration might suggest that middle-aged individuals may have a more pronounced vascular response to PBM, possibly due to age-related changes in skin physiology. A marked site and age effect have been demonstrated on the skin blood flow in literature 26,[37][38][39] . Above mentioned differences in BPU % change might be attributed to the fact that R/NIR might affect the cellular processes in young and middle-aged people differently, considering R/NIR exposure boosts mitochondrial membrane potential and produces ROS when normal cells are exposed, but in cases of low mitochondrial potential due to oxidative stress, excitotoxicity, or electron transport inhibition, light absorption restores potential and reduces ROS production 1,10,11,13,40 when it is applied to improve tissue or muscle injury (diseased or aged cells). ...
Photobiomodulation causes an immediate increase in local blood flow. This study aimed to investigate the effect of 890 nm NIR exposure on local skin blood flow in young and middle-aged healthy subjects. In this placebo-controlled clinical trial, 12 young and 12 middle-aged healthy subjects received either continuous or intermittent NIR exposure (890 nm, 5.1 mW /cm 2 , 4.6 J/cm 2 , and 35.9 J total energy) on the skin of the upper lateral arm. The continuous exposure experiment, used in young subjects only, applied 30 minutes of continuous NIR light (experiment 1). The intermittent exposure experiment, used in both age groups, applied NIR light through 10 cycles of 3 minutes NIR exposure and 2 minutes OFF (for recording blood flow), resulting in 50 minutes of total time. Laser Doppler flowmetry and thermal images were used to monitor local blood flow and skin temperature. In young subjects, continuous NIR exposure compared to placebo significantly increased blood flow for the first 20 minutes post-exposure. Further, in young and middle-aged subjects, intermittent exposure increased blood flow during the whole exposure period and 15 minutes post-exposure. In young subjects, blood flow after continuous NIR exposure was significantly higher than intermittent NIR exposure only for the first 10 minutes. For intermittent exposure comparison between the two age groups, the blood flow was significantly higher in middle-aged subjects. We conclude that NIR PBM increases local skin blood flow in young and middle-aged subjects. The mode of NIR irradiation and the subjects’ age influenced the local skin blood flow response.
... With age, functional changes in all body systems occur in the human body [5], including the cardiovascular system [6,7]. At the microcirculatory level, age-related changes include a decrease in the density of the capillary network [8,9] accompanied by an increase in vascular length [10], impaired microvascular reactivity and increased arterial stiffness [11,12], which leads to an increase in skin perfusion in zones with glabrous skin [13]. It is worth noting that age-related changes in the microcirculatory bed of skeletal muscles become more pronounced with physical exertion, which may be associated with a decrease in vasodilator capacity and a decrease in capillarization [14]. ...
The work is devoted to the study of the physiological variability of the microcirculatory-tissue system (MTS) parameters under normal conditions and during functional tests. The results were obtained in vivo using multimodal wearable analyzers implementing methods of laser Doppler flowmetry and fluorescence spectroscopy. Comprehensive data analysis and calculation of the coefficients of variation of the MTS parameters of the human body for various topographic and anatomical areas of the skin were carried out. The obtained results showed higher values of the coefficient of variation of MTS parameters in the area of the toes and wrists, while the fingers and forehead skin showed lower levers of variation. In all areas of the study, reproducibility of the parameters obtained for the right and left areas of the study is observed.
A comprehensive spectral analysis was used to assess heart rate variability and skin perfusion pattern of limbs in patients with type 2 diabetes mellitus in response to local heating and to identify significant predictors of physiological and pathological changes in the cardiovascular system. An electrocardiogram and skin perfusion on the forearm and foot were measured using Laser Doppler flowmetry at rest and during local heating in both healthy volunteers and patients with type 2 diabetes. The wavelet analysis was applied to Laser Doppler signals and heart rate variability (based on electrocardiogram signals). ROC analysis was used to evaluate significant predictors. The analysis results of patients with type 2 diabetes were compared with healthy controls. The following changes were observed in patients 1) impairment of skin blood flow reserve on the foot during heating, 2) lower amplitude oscillations in heart rate at rest and during heating, 3) an increase in amplitude of oscillations in the skin blood flow from the forearm in intervals related to respiration and heart activity at rest and during heating, 4) a decrease in amplitude of oscillations in the skin blood flow on the foot in the interval related to myogenic activity at rest and in cardiointerval during heating. The parameters of cardiovascular system (energies of heart rate variability at low-frequencies recorded by laser Doppler flowmetry on forearm in intervals related to respiration activity) with high discriminative power were revealed to distinguish patients from healthy subjects in response to local heating; these parameters can be used as markers for early diagnosis of microvascular disorders.
A comprehensive spectral analysis of heart rate variability and skin perfusion of the extremities in patients with type 2 diabetes mellitus in response to local heating and identification of significant predictors of pathophysiological changes in the cardiovascular system has been carried out. Electrocardiogram and skin perfusion on the forearm and foot were measured by laser Doppler flowmetry at rest and under local heating in healthy individuals and diabetic patients. The signals of laser Doppler flowmetry and heart rate variability (according to electrocardiographic data) were subjected to wavelet analysis. Receiver operating characteristic analysis was used to evaluate significant predictors. It was found that in patients, compared with healthy individuals, there was (1) a decrease in the reserve of cutaneous blood flow on the foot under heating, (2) a decrease in the amplitudes of heart rate oscillations at rest and under heating, (3) an increase in the amplitudes of oscillations of laser Doppler flowmetry signals on the forearm in respiratory intervals and cardiac intervals at rest and under heating, and (4) a decrease in the amplitudes of oscillations of laser Doppler flowmetry signals on the foot in the myogenic interval at rest and in the cardiac interval under heating. The parameters of the cardiovascular system (the energy of heart rate variability in the low frequency interval and oscillations of laser Doppler flowmetry signals on the forearm in respiratory interval, which can serve as markers for early diagnosis of microvascular disorders) with high discriminatory power to distinguish patients and healthy individuals in response to local heating were revealed.
Objective
This study was designed to comprehensively evaluate the changes in facial skin biophysical parameters with age, as well the influence of gender differences in populations of Shaanxi Province, China.
Methods
Fourteen skin parameters, including stratum corneum hydration (SCH), transdermal water loss (TEWL), erythema, melanin, R0, R2, R5, R7, F4, gloss, skin surface pH, skin erythema index (a*), wrinkle length, and sebum, were measured by noninvasive instruments in 481 volunteers from Shaanxi Province. Spearman correlation analysis was performed to analyze the relationship between skin parameters and age. Additionally, skin parameters were analyzed for different age groups and different genders.
Results
The results of the study showed a linear decrease in skin surface pH and sebum content with age, and the skin elasticity parameters R0, R2, R5, and R7 decreased significantly at the age of 54–65 years. Wrinkle length showed a linear and increase with age. R5 showed a weak negative correlation with age, R2, R7, and sebum content showed a moderate negative correlation, while wrinkle length showed a strong positive correlation. Considering the effect of gender on skin parameters, the results showed that SCH and gloss were lower in men than in women, while TEWL, erythema, melanin, wrinkle length, and sebum were higher than in women. However, there was no difference in skin elasticity between them.
Conclusion
The facial skin parameters, especially for the wrinkle length, exhibited the strong correlation relationship with ages in Shaanxi Province. Meanwhile, most skin parameters show significant differences with gender, which can provide a reference for future research and development in the field of cosmetics.
Objective:
This study measured normal ranges of microcirculatory parameters in healthy individuals and investigated differences in parameters by age and sex.
Methods:
Participants were enrolled into three groups with equal numbers of male and female: young (20-39 years), middle-aged (40-59 years), and elderly (60-79 years). Sublingual microcirculation images were obtained using the incident dark field (IDF).
Results:
A total of 75 female and 75 male healthy individuals were enrolled. The elderly group had a higher TVD (26.5 [2] vs. 25.2 [1.8]; p = 0.019) and a lower PPV (97 [2] vs. 98 [3]; p = 0.03) than did the young group. In the elderly group, systolic blood pressure (SBP) and mean arterial pressure (MAP) were moderately and positively correlated with MFI score (r = 0.407, p < 0.05, and r = 0.403, p < 0.05, respectively). The female participants had a lower MFI score than did the male participants (2.9 [2.8-3] vs. 3.0 [2.9-3]; p = 0.015).
Conclusions:
This study revealed the range of microcirculatory parameters between different ages and sexes in healthy individuals. We found that blood pressure levels were correlated with microcirculatory parameters, especially in elders and female.
: To assess nailfold capillary density and dimensions in patients with primary Raynaud's phenomenon (PRP), limited cutaneous systemic sclerosis (LSSc) and diffuse cutaneous SSc (DSSc), and healthy control subjects.
: Using the technique of nailfold video capillaroscopy, capillary density and dimensions were averaged from all visible capillaries in a 3 mm length of the nailfold from right and left ring fingers of each subject. Twenty healthy control subjects, 15 patients with PRP, 13 patients with DSSc and 21 patients with LSSc were examined. Intra-observer and inter-observer variability were calculated in 18 and 23 patients, respectively.
: There were significant trends for capillary density to fall and for all dimensions to rise across the four groups (P < 0. 0001 for density and all dimensions, order healthy controls, PRP, DSSc and LSSc). Intra- and inter-observer reproducibility studies showed that although there was good correlation between and within observers, the limits of agreement were between +/-25-50% indicating lack of reproducibility.
: Microcirculatory abnormalities can be quantified using the technique of video capillaroscopy and were most marked in patients with LSSc.
The cutaneous microcirculation is organized as two horizontal plexuses. One is situated 1-1.5 mm below the skin surface and the other is at the dermal-subcutaneous junction. Ascending arterioles and descending venules are paired as they connect the two plexuses. From the upper layer, arterial capillaries rise to form the dermal papillary loops that represent the nutritive component of the skin circulation. There are sphincter-like smooth muscle cells at the point where the ascending arterioles divide to form the arteriolar component of the upper horizontal plexus. At the dermal-subcutaneous junction, there are collecting veins with two cusped valves that are oriented to prevent the retrograde flow of blood. Laser Doppler flowmetry has demonstrated vasomotion of red cell flux localized to the sites of ascending arterioles. The simultaneous recording by laser Doppler flowmetry of red cell flux and the concentration of moving red blood cells from individual sites allows one to construct topographic maps of these two values. These two maps, based on initial studies using correlative skin biopsies, can define 1 mm3 volumes of skin that are predominantly arteriolar in composition, venular in composition, or essentially devoid of all microvascular elements. The electron and light microscopic features that define the microvascular segments, when coupled with that ability of laser Doppler flowmetry to define the predominant microvascular segments under the probe, allow one to study both the mechanisms of normal physiologic states and the pathogenetic mechanisms underlying pathologic skin disorders in which the microvasculature plays a predominant role.
Microvascular changes in 32 biopsies of normal human skin were observed using electronic computer image analysis. Statistical analysis showed a decrease in microvasculature with increase of age, with significant decreases appearing at ages greater than or equal to 20, suggesting that the changes are closely related to aging of human skin.
Few studies have attempted to quantitatively assess in vivo changes in the microvasculature with age.
The objective was to assess in vivo structural and functional changes in the cutaneous microvasculature with aging and to analyze the contribution of the microvasculature to skin color.
Video capillaroscopy, in conjunction with fluorescein angiography, and laser-Doppler flowmetry were used to compare elderly and young normal volunteers. Skin color differences were assessed with a handheld color reflectance meter. A photoexposed site, the forehead, and the relatively photoprotected ventral forearm were studied to differentiate photoaging from chronologic aging.
Dermal papillary loops were significantly reduced in old skin compared with young skin (forehead by 40%; forearm by 37%). Horizontal vessels showed increased volume fraction in elderly forehead and forearm skin. Laser-Doppler studies demonstrated no significant differences between young and old skin; indeed, hyperemic responsiveness appeared more rapid in the elderly. Color measurements showed elderly skin, particularly in men, to be significantly darker and redder.
A marked loss in dermal nutritional vessel density and surface area for exchange is a feature of both chronologic aging and photoaging.
Laser Doppler flowmetry is an excellent noninvasive technique for the measurement of cutaneous microcirculation. The list of applications of laser Doppler flowmetry in dermatology is long. It can be applied to monitor inflammation caused by various drugs, chemicals, and allergens related to blood flow. To measure certain inflammatory reactions a combination of other bioengineering measurements is desirable. Flaps can be monitored, and burn depth measured by laser Doppler flowmetry. Through blood flow measurement, the pathophysiology of various skin diseases can be verified and certain treatments can be partially monitored. Although it is not as directly applicable to daily clinical practice, except in a few cases, laser Doppler flowmetry is a very useful technique in various kinds of dermatologic research.
Many methods are available today for clinical evaluation of the blood supply to an extremity or part of an extremity, some of which are excellent for determining the presence and severity of arterial and venous disorders. These methods, however, do not give any information on the microvascular status of the diseased areas. This is particularly true for the skin circulation, which has a rather complex vascular network with nutritional and thermoregulatory vessels, arteriovenous shunts, etc. The most useful method for clinical evaluation of the skin capillary circulation is vital capillary microscopy. The skin capillaries in an area with a reduced microcirculation change in structure, and it is possible to evaluate the viability of the skin by microscopic studies of these capillary changes. Both morphology and blood flow can be investigated. By using different intravital fluorescent dyes, e.g. sodium fluorescein and indocyanine green, the microvascular dynamics, flow distribution and microvascular permeability can also be studied. The total skin microcirculation can be evaluated by Laser Doppler fluxmetry, which measures primarily the blood flow in the thermoregulatory vascular bed, i.e. the subpapillary arterial and venous plexa. It is easy to use in clinical practice, but interpretation of the results can sometimes be difficult. Measuring transcutaneous oxygen tension has for many years been used in clinical routine to evaluate the viability of skin in patients with vascular disorders. It has recently been shown that inhalation of oxygen may induce vasoconstriction in healthy subjects and in patients with moderate arterial insufficiency, but an increase of the skin microcirculation in areas of severe ischaemia. By using different combinations of the above mentioned microcirculatory techniques, valuable information can be gained regarding pathophysiological phenomena of the microcirculation in many diseases, e.g. vascular disorders, collagenosis. Raynaud's phenomenon, diabetes and hypertension. Using techniques for both macro- and microcirculation is also of great importance for evaluating the effect of therapeutic procedures in several of these disorders.
Using intravital fluorescence microscopy in the ears of hairless mice, we determined skin microvascular adaptations during the process of aging from juvenile to adult and senescent life (6-78 wk). Despite an increase of ear area within the first 36 wk, the number and branching pattern of both arteriolar and venular microvessels remained constant during the whole life period. Both arterioles and venules exhibited an increase in length, diameter, and intervascular distance up to the age of 36 wk. With the increase of the size of the ears, the observation that cutaneous capillary density remained unchanged implied new capillary formation. During aging to 78 wk, capillary density in the ears was reduced to approximately 40%. Functional analysis revealed an appropriate hyperemic response to a 2-min period of ischemia during late juvenile and adult life, which, however, was markedly reduced during senescence. Thus, except for capillaries, there is no indication for age-related new vessel formation. The process of aging from adult to senescent life does not cause any significant remodeling but is associated with a decrease of nutritive perfusion and a functional impairment to respond to stimuli such as ischemia.
The cutaneous microcirculation shows a significant heterogeneity. With high-resolution two-dimensional laser Doppler perfusion imaging (LDPI), spatial and temporal reproducible perfusion measurements can be reached. The objective of this study was the quantification of skin perfusion in 20 defined skin areas with LDPI, in 60 healthy young and old volunteers. The perfusion of the face was significantly higher than that of the trunk and extremities. The highest perfusion values were seen at the lips, 1.47 arbitrary units (AU), followed by the chin (0.99 AU), the nose (0.95 AU), the forehead (0.73 AU) and the cheek (0.72 AU). Mean perfusion, between 0.40 and 0.49 AU, was seen at the extremities and at the trunk. The lowest perfusion was found at the bottom (0.37 AU), on the back of the foot (0.36 AU) and on the soles (0.31 AU). There was a tendency to show higher perfusion values in men than in women (0.60 +/- 0.31 vs. 0.53 +/- 0.26 AU). Age-related differences in perfusion could not be demonstrated. In the evaluation of the perfusion of pathological skin, regional perfusion differences must be considered, whereas moderate age or gender differences between different investigation groups can be tolerated.
Anatomic location and depth of ectasia of port-wine stains (PWSs) are important prognostic indicators when evaluating treatment options for patients. Videomicroscopy permits subsurface evaluation of PWSs, thereby allowing determination of the depth of the ectatic vessels.
Our purpose was to determine whether location of PWSs corresponds to the depth of the ectatic vessels.
Seventeen patients presenting for evaluation or treatment of PWSs underwent videomicroscopy with a Video Loupe 7EX microscope. Data were recorded by location of the PWS as a type 1 lesion (blobs or globular structures) corresponding to ectasia of the superficial capillary loops, a type 2 lesion (rings) corresponding to ectasia of the deeper horizontal plexus, or a mixed pattern.
PWSs in areas that typically respond well to laser treatment (V3, neck, and trunk) were more likely to have a superficial type 1 pattern. PWSs in areas that have a poorer response to therapy (V2, distal extremities) were more likely to have a deeper type 2 pattern.
We found that patients with lesions in the V3 dermatome and on the trunk and neck have more superficially ectatic vessels, whereas those lesions in dermatome V2 and on the distal extremities have more deeply placed vessels. Further studies are needed to determine whether videomicroscopy can be used to preoperatively predict treatment results.