CPD
Carboxypeptidase D precursor (EC 3.4.17.22) (Metallocarboxypeptidase D) (gp180)
PublicationsПравить
Most thyroid cancer are incidentally diagnosed. However, little is known on the different modalities of incidental diagnosis in adult versus older patients. We retrospectively analyzed data from 440 patients consecutively diagnosed with differentiated thyroid cancer (DTC) in a single institution. Modalities of diagnosis were categorized as follows: (A) clinically diagnosed, nonincidental cases; (B) incidental during carotid power-duplex (CPD); (C) incidental during neck imaging other than carotid power-duplex; (D) incidental during imaging workup of thyroid dysfunction or at histological examination after thyroidectomy for benign lesions. Demographics, histology and follow-up were compared between adult (<65 years) and older (≥65 years) patients according to the different modalities of diagnosis. A total of 363 and 67 cases were recorded in adult and older patients, respectively with incidental proportions of 79% and 85%, respectively. A P < 0.001 significant difference in the modality of diagnosis was found between adult and older subjects, the latter presenting with a higher prevalence of Group B. In the nonincidental group, papillary histotype, larger size, and extrathyroidal invasion were more frequently observed in older subjects. Disease-free survival was comparable between adult and older subjects in the incidental cases, whereas it was reduced, though not significantly, in older subjects. Incidental cases of DTC are more frequently diagnosed in the old subjects and are mainly due to CPD. Disease-free survival is comparable between adult and older subjects in both incidental and nonincidental cases, although it may be slightly reduced in nonincidentally diagnosed older patients.
Keywords
- Aging
- Incidental
- Thyroid cancer
The prevalence of chronic obstructive pulmonary disease (COPD) and lung emphysema increases with age and both lung diseases are again risk factors for lung cancer. Since a reduced capacity of fibroblasts for proliferation is a good indicator of tissue aging, we studied the cell proliferation of lung fibroblasts from normal and tumor tissue of lung cancer patients depending on lung comorbidities. Fibroblasts were isolated from tumor and normal lung tissue of 40 lung cancer patients. Cumulative population doubling (CPD) was determined to assess the proliferation capacity, and the PCR technique was used to measure telomere lengths. Since many patients had previously been exposed to severe air pollution, we also studied the effect of air pollution particles on the fibroblast CPD in vitro. Fibroblasts from tumor and normal lung tissue had comparable CPDs; however, the CPD of fibroblasts from both tumor and normal lung tissue was significantly reduced in patients also suffering from COPD. This CPD reduction was highest in COPD patients who had already developed emphysema or were smokers. A significant correlation between CPD and telomere length was identified only for fibroblasts of non-COPD patients. Further studies also showed an adverse effect of air pollution particles on the CPD of lung fibroblasts. Lung cells of COPD patients are characterized by accelerated senescence which must have been initiated prior to lung tumorigenesis and cannot depend on telomere shortening only. In addition to smoking as a known risk factor for COPD and lung cancer, air pollution particles could be another reason for the accelerated senescence of lung cells.
MeSH Terms
- Cell Proliferation
- Cells, Cultured
- Female
- Fibroblasts
- Humans
- Lung
- Male
- Pulmonary Disease, Chronic Obstructive
- Tumor Cells, Cultured
Keywords
- Air pollution
- Cancer
- Cellular senescence
- Fibroblasts
- Smoking
We assessed clinicians' continuing professional development (CPD) needs at family practice teaching clinics in the province of Quebec. Our mixed methodology design comprised an environmental scan of training programs at four family medicine departments, an expert panel to determine priority clinical situations for senior care, a supervisors survey to assess their perceived CPD needs, and interviews to help understand the rationale behind their needs. From the environmental scan, the expert panel selected 13 priority situations. Key needs expressed by the 352 survey respondents (36% response rate) included behavioral and psychological symptoms of dementia, polypharmacy, depression, and cognitive disorders. Supervisors explained that these situations were sometimes complex to diagnose and manage because of psychosocial aspects, challenges of communicating with patients and families, and coordination of interprofessional teams. Supervisors also reported more CPD needs in long-term and home care, given the presence of caregivers and complexity of senior care in these settings.
MeSH Terms
- Adult
- Aged
- Aging
- Clinical Competence
- Cross-Sectional Studies
- Family Practice
- Female
- Focus Groups
- Health Services Needs and Demand
- Health Services for the Aged
- Humans
- Internship and Residency
- Male
- Middle Aged
- Qualitative Research
- Surveys and Questionnaires
Keywords
- aging
- besoins de formation
- faculty development
- family practice
- formation professorale
- graduate programs
- médicine familiale
- programmes d’études supérieures
- supervision
- training needs
- vielliessement
Continuing professional development (CPD) is an obligation for all Australasian geriatricians; however, there are no systematic data regarding Australian and New Zealand geriatricians' satisfaction with, and preferences for, CPD. To inform understanding of Australasian geriatricians' satisfaction with, and preferences for, CPD. An electronic survey to collect data relating to demographics, current CPD activities, preferred CPD activities and perceived major barriers to CPD was distributed to 706 geriatricians in Australia and New Zealand. Two hundred and thirteen (30%) responses were received. Respondents commonly reported CPD through participation in conferences (n = 205 (96%)) and research/educational activity (n = 146 (70%)). Most respondents agreed that the annual scientific meeting (n = 168 (79%)) and state-based meetings (n = 135 (63%)) are valuable for their CPD. Respondents perceived their professional (n = 155 (73%)) and non-professional (n = 21 (57%)) commitments as the major barriers to quality CPD. Respondents supported additional electronic CPD resources being made available, improved integration of assessment in CPD activities and flexible methods of CPD participation to meet the diverse needs of geriatricians. Respondents perceived the face-to-face CPD opportunities currently available to them as valuable for their CPD but seek additional, flexible products to enable CPD participation based on individual needs and preferences.
MeSH Terms
- Australia
- Education, Medical, Continuing
- Female
- Geriatricians
- Humans
- Male
- New Zealand
- Personal Satisfaction
- Staff Development
- Surveys and Questionnaires
Keywords
- continuing
- education
- geriatrics
- medical
- staff development
The Royal Australasian College of Surgeons (RACS) has been innovative in developing core competencies, which provide a framework for assessing performance and a 'Code of Conduct', for the lifelong journey of all surgeons. The older surgeon may face significant challenges, having passed their peak, with a lower volume of cases, and potentially increased complications. They also face the challenges of retiring from active clinical practice with its logistical and psychological dilemmas. The RACS has, therefore, put in place several initiatives to deal with these dilemmas. The Senior Surgeons' Group, which conducts annual 'Building Towards Retirement' workshops, has been the driving force behind these initiatives. The group has a regular program in the RACS Annual Scientific Congress, including the multidisciplinary session 'The ageing specialist - challenges for regulators: hypothetical' which took place in 2014, and some of its members are part of a multidisciplinary team with an approach to adapting to ageing that encourages self-reflection and self-monitoring. It has also influenced the RACS Council to change the continuing professional development (CPD) regulations to include requirements for ageing surgeons regards health maintenance, peer reviews, and modified requirements to satisfy CPD completion. The RACS offers a variety of other opportunities for the ageing surgeon to remain active in college activities.
MeSH Terms
- Aging
- Anesthesiology
- Clinical Competence
- Humans
- Psychiatry
- Retirement
- Surgeons
Keywords
- ageing
- cognitive function
- surgeons
Age-related effects of the vascular wall have been associated with several hemodynamic dysfunctions, including medial vascular calcification. Vascular aging has been traditionally addressed using proliferative senescence of vascular smooth muscle cells (VSMC) in vitro, which induces osteoblastic transition and favors calcification in vitro. In this work, we have analyzed the relationship between organismal aging and proliferative senescence by comparing the proliferative aging of VSMC obtained from young, mature, and old rats (2-, 12-, and 24-month cell lines [CL], respectively). VSMC proliferated to more than 100 cumulative population doublings (CPD) without evidence of proliferative senescence, most likely as a consequence of telomerase induction. The apoptosis rate increased with CPD in all three CL, but the oxidation status of the cells was not modified. The magnitude of all gene expression changes caused by CPD was higher than the magnitude of the changes caused by donor age: the expressions of VSMC markers α-actin and SM22α decreased, while the expressions of transcription factors Msx2 and Runx2 and of bone morphogenetic protein-2 increased. Treatment of the cells with 2 mmol/L Pi revealed that the intensity of the effect of CPD on calcium deposition was greater than the effect of donor age. In conclusion, the proliferative lifespan of VSMC magnifies the effect of donor age on the osteoblastic transition of VSMC, therefore suggesting that in vivo vascular aging changes can be less dramatic than what is shown by in vitro aging.
Keywords
- Aging
- proliferation
- senescence
- vascular calcification
- vascular smooth muscle cells
Senescence-associated β-galactosidase (SA-β-Gal) is a widely used marker of senescent cells in vitro and in vivo. In this report, young and senescent human peritoneal mesothelial cells (HPMCs) and fragments of the omentum, from which these cells were isolated, were subjected to simultaneous examination of SA-β-Gal using two methods, i.e. cytochemical and fluorescent methods. The results obtained were confronted with the cumulative number of population doublings (CPD) and the calendar age of the tissue donor. The study showed that senescence of HPMCs proceeds with either an increased percentage of SA-β-Gal-positive cells or increased enzyme activity. Cytochemical SA-β-Gal staining in early-passage cultures negatively correlated with CPD values but not with donor age in both cell cultures and omentum specimens. Conversely, SA-β-Gal activity measured with the fluorescence method rose in proportion to the calendar age of the donor either in early-passage cultures or in primary cell isolates from omental tissue. At the same time it was not related to the CPD values. These findings may suggest that with respect to at least peritoneal mesothelial cells, the cytochemical and fluorescent methods of SA-β-Gal detection, though complementary, are informative for different levels of aging, i.e. the cytochemical approach for senescence in vitro and the fluorescence-based technique for organismal aging in vivo.
MeSH Terms
- Adult
- Aged
- Aging
- Female
- Fluorescence
- Humans
- Male
- Middle Aged
- Young Adult
- beta-Galactosidase
Management of chronic uremia in elderly patients presents several clinic and organizational difficulties. Hemodialysis (HD) and chronic peritoneal dialysis (CPD) are both available for the elderly, and the choice depends on the individual, clinical and familial conditions. Several reports have compared the outcomes for older patients treated by HD or peritoneal dialysis, with those for younger or older patients undergoing peritoneal dialysis. CPD is a successful dialysis option for elderly patients, in both patient and technique survival terms. All nutritional parameters are of pivotal importance. Several barriers, such as medical and social factors, physician bias, late referral and education irrespective of the needs of older patients, influence the choice of CPD. The development of assisted peritoneal dialysis, using community-based nurses or health care assistants, can overcome some of the barriers and enable frail older patients to have home-based dialysis treatment. Increasing age is associated with higher peritonitis rates among patients who started CPD in the 1990s, while age is not associated with peritonitis in more recent CPD cohorts, and no greater frequency of adverse outcomes of peritonitis has been seen among those who began CPD after the year 2000. In elderly dialysis patients, the management of quality of life (QOL) is important as well as adequacy of dialysis, nutritional status and survival rate. To obtain a good standard of QOL, it is essential to select carers who are properly educated and who can access an adequate support system, both physical and psychological, to help them cope with their burden.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Chronic Disease
- Comorbidity
- Health Services for the Aged
- Humans
- Kidney Diseases
- Nutritional Status
- Patient Selection
- Peritoneal Dialysis
- Peritonitis
- Quality of Life
- Risk Assessment
- Risk Factors
- Treatment Outcome
Several studies have analyzed modulation of gene expression during physiological ageing with interesting, but often contradictory results, depending on the model used. In the present report we compare age-related metabolic and synthetic parameters in human dermal fibroblasts (HDF) isolated from young and old subjects (ex vivo ageing model) and cultured from early up to late cumulative population doublings (CPD) (in vitro ageing model) in order to distinguish changes induced in vivo by the aged environment and maintained in vitro, from those associated with cell senescence and progressive CPD. Results demonstrate that fibroblasts from aged donors, already at early CPD, exhibit an impaired redox balance, highlighting the importance of this parameter during ageing, even in the presence of standard environmental conditions, which are considered optimal for cell growth. By contrast, several proteins, as those related to heat shock response, or involved in endoplasmic reticulum and membrane trafficking, appeared differentially expressed only during in vitro ageing, suggesting that, at high CPD, the whole cell machinery becomes permanently altered. Finally, given the importance of the elastic component for a long-lasting connective tissue structural and functional compliance, this study focuses also on elastin and fibulin-5 synthesis and deposition, demonstrating a close relationship between fibulin-5 and ageing.
MeSH Terms
- Adolescent
- Aged, 80 and over
- Aging
- Cells, Cultured
- Cellular Senescence
- Dermis
- Elastin
- Extracellular Matrix Proteins
- Female
- Fibroblasts
- Gene Expression Regulation
- Humans
- Models, Biological
To calculate the average lens density (ALD) and nuclear lens density (NLD) using Scheimpflug images and to determine their correlation with logarithmic minimal angle resolution (logMAR) best-corrected visual acuity (BCVA), contrast sensitivity (CS), and lens grading based on the Lens Opacities Classification System (LOCS) III. Cross-sectional observational study. One hundred ten patients with age-related nuclear cataract. The logMAR BCVA was recorded using Early Treatment Diabetic Retinopathy Study charts and photopic contrast-sensitivity using CSV-1000LV (Vector Vision, Greeneville, OH). Fifty Scheimpflug images (Pentacam, Oculus, Germany) covering 360 degrees of the lens were obtained for 1 eye of each patient after dilation. All Scheimpflug images were exported to ImageJ software (NIH, Bethesda, MD) for analysis wherein the ALD and NLD (using a mask applied to the lens nuclear area) were calculated in pixel-intensity units. Repeatability was determined using coefficient of variation (CoV) and intraclass correlation coefficient (ICC). Lens opacity on slit-lamp images was graded using LOCS III for nuclear opalescence (NO) and nuclear color (NC). We evaluated ALD and NLD on Scheimpflug images and their correlation with NO and NC LOCS III grading, BCVA, and photopic CS. The ICC for ALD and NLD were 0.983 and 0.99, respectively; the CoV were 3.92 /-1.76% and 2.57 /-0.74%, respectively. The ALD correlated with NO (r = .774; P<0.001), NC (r = .732; P<0.001), BCVA (r = 0.696; P<0.001), and CS at 3 cycles per degree CPD (P = 0.011), 6, 12, and 18 CPD (P<0.001). The NLD correlated with NO (r = .859; P<0.001), NC (r = .81; P<0.001), BCVA (r = .760; P<0.001), CS at 3 CPD (P = 0.002), 6, 12, and 18 CPD (P<0.001). The NLD had a significantly stronger correlation with BCVA (P<0.05), NO (P<0.01), NC (P<0.01), and CS at 6 CPD (P<0.01) and 12 CPD (P<0.005) compared with ALD. Repeatable 360 degrees lens density measurements were obtained using Scheimpflug imaging. A stronger correlation was observed between NLD and LOCS III grading, BCVA, and photopic CS than with ALD. The NLD is an objective and repeatable method for assessment of lens density, which could be helpful in longitudinal studies monitoring nuclear cataracts.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cataract
- Contrast Sensitivity
- Cross-Sectional Studies
- Diagnostic Techniques, Ophthalmological
- Female
- Humans
- Lens Nucleus, Crystalline
- Male
- Middle Aged
- Photography
- Vision Tests
- Visual Acuity
Cotinine is the most common biomarker used to assess nicotine exposure and abstinence. It can be measured in various matrices including saliva, plasma, and urine. Previous research with adults has shown high correlations between saliva and plasma cotinine concentrations. However, the research has not examined this relationship in adolescents. Additionally, variability in saliva flow and metabolism across gender, ethnicity, and age may impact the relationship between saliva and plasma cotinine concentration. Our aim was to examine the relationship between saliva and plasma cotinine concentration in a group of nicotine-dependent adolescent smokers. Additionally, we examined these correlations across gender, ethnicity and age. The sample consisted of 66 adolescent smokers (age 15.1 /-1.3, 63.6% girls, 66.7% European American, CPD 18.3 /-8.5, FTND 7.1 /-1.3). Saliva and plasma specimens were collected before the treatment phase of a nicotine replacement therapy trial and analyzed. The relationship between saliva and plasma cotinine concentration was analyzed using Pearson's correlation coefficients. We performed a secondary analysis using multiple regressions to compare correlations across race, gender and age. Results indicated a positive correlation between saliva cotinine and plasma cotinine concentration (r=0.84, p<0.001). Differences in correlations across age were significant (t=3.03, p<0.01). Differences across ethnicity approached significance (t=-1.93, p=0.058). Future research should seek to further validate saliva-to-plasma cotinine concentration ratios in adolescents as well as characterize saliva-to-plasma concentration differences and their underlying mechanisms.
MeSH Terms
- Adolescent
- Aging
- Cotinine
- Data Interpretation, Statistical
- Ethnic Groups
- Female
- Humans
- Male
- Saliva
- Salivation
- Sex Characteristics
- Smoking
- Tobacco Use Disorder
Test the hypothesis that depressed hospitalized patients with congestive heart failure (CHF) and/or chronic pulmonary disease (CPD) are no different from depressed patients with other medical disorders, and so can be treated similarly. Consenting patients aged 50 or over consecutively admitted to the medical services at Duke University Medical Center and three community hospitals were screened for depressive disorder using the Structured Clinical Interview for Depression (SCID-IV). Characteristics of patients reflecting vulnerability, stressors, and coping resources were assessed. CHF/CPD patients with major (n = 413) and minor (n = 587) depression were compared to depressed patients with other medical disorders (n = 63). Among those with major depression, patients with CHF/CPD differed from those with other medical disorders in having less severe depression and less severe cognitive impairment, but greater physical illness severity. Among those with minor depression, CHF/CPD patients tended to be older and, as with major depression, had less severe depression and more severe medical illness. These findings were largely confirmed when CHF and CPD patients were examined separately. Depressive disorders in CHF/CPD patients are similar to those in patients with other medical disorders. However, they may be associated with less severe depressive symptoms and more severe physical illness than depressed patients with other medical disorders. These findings help to identify the unique ways in which depressive disorder manifests itself in hospitalized patients with chronic heart and lung disease that may impact their management.
MeSH Terms
- Adaptation, Psychological
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Depressive Disorder
- Depressive Disorder, Major
- Female
- Geriatric Assessment
- Health Status
- Heart Failure
- Hospitalization
- Humans
- Lung Diseases
- Male
- Middle Aged
- Odds Ratio
- Psychiatric Status Rating Scales
- Severity of Illness Index
- Stress, Psychological
Ultraviolet radiation (UVR)-induced photoproducts can be measured by a number of methods. The newly developed 32P-postlabelling method is feasible in molecular epidemiological studies due to its sensitivity, specificity and little amount DNA needed. We applied the 32P-postlabelling method to investigate the induction and repair of photoproducts (cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts) after UVR in human skin in situ and studied the effects of age, skin type and gender. The study included 30 subjects aged 32-78 years. The photoproduct induction levels varied 7- to 15-fold between the individuals tested. All four types of photoproducts were induced at a higher frequency in the older population (>/=50 years) than in the younger population (<50 years). Individuals with skin type I and II had a higher CPD induction frequency than individuals with skin type III and IV. In both cases, the differences in thymidylyl (3'-5') thymidylyl (3'-5')-2'-deoxycytidine induction reached statistical significant levels (p<0.05). Photoproduct repair rates 24 h and 48 h after UV irradiation showed a large inter-individual variation. No clear effects of age, skin type or gender on DNA repair could be detected. Our data suggest that UV-induced DNA photoproduct levels increase with age.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aging
- Biopsy
- Chromatography, High Pressure Liquid
- DNA
- DNA Repair
- Female
- Humans
- Kinetics
- Male
- Middle Aged
- Phosphorus Radioisotopes
- Pyrimidine Dimers
- Regression Analysis
- Sex Factors
- Skin
- Ultraviolet Rays
Diploid human skin fibroblasts derived from an 82-year-old donor with a 21-28 cell population doubling (CPD) range (where 28 CPD marked the end of the in vitro life span of the cells) were fused with whole L cells, L karyoplasts and L cytoplasts. The proportion of human nuclei incorporating tritiated thymidine after fusion was measured autoradiographically. Statistically significant increases in the labeling indices were found in the human nuclei in hybrid, heterodikaryon and cybrid cells when compared to control unfused human cells. Fusion of human diploid fibroblasts with human cytoplast derived from cells of the same CPD showed no significant changes in the labeling indices of the human nuclei.
MeSH Terms
- Aged
- Aging
- Animals
- Cell Fusion
- Cell Line
- Cell Nucleus
- DNA
- Diploidy
- Fibroblasts
- Humans
- In Vitro Techniques
- L Cells
- Mice
- Mitotic Index
- Skin
- Thymidine
Within a series of studies on microcirculation in the aged, the conjunctival vessels were investigated by means of the intravital microscope in the course of intravenous infusion or prolonged administration of various drugs (xanthinol nicotinate, buflomedil, CPD-choline). During and after the treatment a better perfusion of the small conjunctival vessels (terminal capillary network) was observed, as well as the appearance of collaterals and a reduction of intravascular red cell aggregation. On the basis of these results a further direct demonstration of the vasoactive effect of the drugs under study could be given.
MeSH Terms
- Aged
- Aging
- Collateral Circulation
- Conjunctiva
- Erythrocyte Aggregation
- Humans
- Microcirculation
- Vasodilator Agents
Studies on microcirculation in the elderly include observations in the small vessels of the bulbar conjunctiva and of the nailbed with respect to a classification of the findings according to a number of semeiologic criteria (diameter and shape alterations, terminal capillary network, intravascular red cell aggregation). In vascular diseases of the elderly there are typical alterations of the capillaroscopic findings in the bulbar conjunctiva and in the nailbed, particularly in cases of arteriosclerosis, arterial hypertension, diabetic microangiopathy, heart failure, ischemic myocardiopathies. During the treatment with some vasoactive drugs (nicotinic acid and its derivatives, buflomedil, CPD-choline) there are marked modifications of the small conjunctival vessels, with evident dilatations, appearance of collaterals, increased homogeneity of the blood flow, better evidence of the capillary network and reduction of intravascular red cell aggregation.
MeSH Terms
- Aged
- Aging
- Arteriosclerosis
- Cytidine Diphosphate Choline
- Diabetes Mellitus
- Erythrocyte Aggregation
- Heart Failure
- Humans
- Hypertension
- Microcirculation
- Nails
- Niacin
- Pyrrolidines
Primary human skin fibroblasts derived from the abdomen of 45 female donors of the four age groups 1-20, 20-40, 40-60, and 60-80 years were studied in primary explant, in primary low-density mass cultures, and in primary clonal populations in vitro. As a function of the age of the donor, primary mitotic and postmitotic fibroblasts in the three primary cell systems analysed represent heterogeneous populations with reproducible changes in the proportions of the mitotic fibroblasts MF I, MF II, MF III, and postmitotic fibroblasts PMF IV, PMF V, PMF VI, and PMF VII. These findings make it very likely that equivalent cell types exist in the connective tissue of skin in vivo, and that these cells undergo reproducible changes in the proportions of the mitotic and postmitotic counterparts in vivo as a function of the age of the donor. Secondary mitotic human skin fibroblast populations of the cell line HH-8 in vitro underwent 53.6 /- 6.0 cumulative population doublings (CPD) in 302 /- 27 days. If appropriate methods are applied, mitotic fibroblasts differentiate spontaneously into postmitotic fibroblasts which are kept in stationary cultures for up to 305 /- 41 additional days. As a function of the CPD level and of the duration of stationary culture, secondary mitotic and postmitotic fibroblast populations are heterogeneous populations with reproducible changes in the proportions of mitotic fibroblasts MF I, MF II, and MF III, and postmitotic fibroblasts PMF IV, PMF V, PMF VI, and PMF VII. The seven secondary fibroblast cell types show differentiation-dependent and cell-type specific patterns of [35S]methionine polypeptides in total soluble cytoplasmic and nuclear proteins, in secreted proteins, and in membrane bound proteins. These findings make it very likely that the morphologically recognizable primary and secondary fibroblasts differentiate spontaneously along a seven stage terminal cell lineage MF I - MF II - MF III - PMF IV - PMF V - PMF VI - PMF VII in three compartments of the fibroblasts stem cell system.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cell Cycle
- Cell Differentiation
- Cells, Cultured
- Child
- Child, Preschool
- Female
- Fibroblasts
- Humans
- Infant
- Middle Aged
- Skin
- Stem Cells
The introduction and repair of DNA lesions are generally heterogeneous with respect to different genomic domains. In particular, the repair of helix-distorting damage, such as the cyclobutane pyrimidine dimers (CPD) induced by ultraviolet light occurs selectively in expressed genes. This is due in large part to the preferential repair of transcribed DNA strands, which is then reflected in a bias toward mutagenesis from persisting lesions in nontranscribed strands. Consequently, determination of overall genomic repair efficiencies may not be a good indicator of cellular sensitivity to agents that damage DNA. Although some studies suggest an age-related accumulation of altered nucleotides in DNA, we do not know the intragenomic distribution of those changes and whether they are relevant to the physiological aspects of aging. Subtle changes in the pattern of preferential repair during maturation could have profound effects on cell and tissue function. DNA repair has been analyzed in differentiating cell systems as possible models for aging. We have observed attenuated overall repair of CPD in differentiated rat myoblasts or PC12 neuron-like cells. In both model systems, several expressed genes have been shown to be repaired relatively efficiently but without strand specificity. In another model system of human HT1080 fibroblasts differentiating in the presence of dexamethasone, we demonstrated enhanced repair in the gene for plasminogen activator inhibitor I whose transcription is induced and, correspondingly, a reduced repair rate in the urokinase plasminogen activator gene whose transcription is suppressed. We conclude that any attempted correlation of the phenomena of aging with DNA repair should focus on the relevant genes in the tissue of interest.
MeSH Terms
- Aging
- Animals
- Cell Differentiation
- Cells, Cultured
- DNA Damage
- DNA Repair
- Gene Expression
- Genes
- Humans
- In Vitro Techniques
- Muscles
- Neurons
- PC12 Cells
- Pyrimidine Dimers
- Rats
- Transcription, Genetic
- Wound Healing
Several experiments conducted by our group over a period of 6 years have shown that nutritional stress, especially protein and/or calorie deprivation, leads to many, often dramatic, changes in the immune responses of mice, rats, and guinea pigs. Chronic protein deprivation (CPD) has been shown to create an enhancing effect on the cell-mediated immune responses of these animals. Humoral responses under CPD conditions were most often found to be depressed, but sometimes were unaffected, depending on the nature of the antigen employed. Chronic protein deprivation, consistent with the pattern just mentioned, improved tumor immunity by depressing production of B-cell blocking factors, and, in at least one instance, resistance to development of mammary adenocarcinoma in C3H mice was associated with evidence of increased numbers of T suppressor cells. Profound nutritional deficits (less than 5% protein per total daily food intake) depressed both cellular and humoral immunity. Early, though temporary, protein deprivation caused a long-term depression of both cellular and humoral immunity also, with the humoral component being the first to recover. Manipulation of protein and calories was found to have a profound effect on certain autoimmune conditions. Diets high in fat and low in protein favored reproduction but shortened the life of NZB mice, whereas diets high in protein and low in fat inhibited development of autoimmunity and prolonged life. Chronic moderate protein restriction permitted NZB mice to maintain their normally waning immunologic functions much longer than mice fed a normal protein intake. Further, the low-protein diet was associated with a delay in development of manifestations of autoimmunity. Decreasing dietary calories by a reduction of fats, carbohydrates, and proteins more than doubled the average life span of (NZB X NZW)F1 mice, a strain prone to early death from autoimmune disease. Histopathologic studies using immunofluorescent microscopy revealed that the development of the renal lesions caused by the deposition of antigen-antibody complexes, which is so characteristic of these mice, was markedly delayed.
MeSH Terms
- Anemia, Hemolytic
- Animals
- Antibody-Producing Cells
- Autoimmune Diseases
- Chronic Disease
- Cytotoxicity Tests, Immunologic
- Disease
- Graft Rejection
- Graft vs Host Reaction
- Hemolytic Plaque Technique
- Immunity
- Immunity, Cellular
- Longevity
- Male
- Mammary Glands, Animal
- Neoplasms
- Nutrition Disorders
- Protein Deficiency
- Spleen
- T-Lymphocytes