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Age Apr 1999Multiple pathways are involved in accurate synthesis and distribution of DNA during replication, repair and maintenance of genomic integrity. An increased error rate,...
Multiple pathways are involved in accurate synthesis and distribution of DNA during replication, repair and maintenance of genomic integrity. An increased error rate, abovethe spontaneous mutation baseline, has been implicated in carcinogenesis and aging. Moreover, cytogenetic abnormalities are increased in Down's, Edwards', Patau's, and Klinefelter's syndromes with increasing maternal age, and in Marfan's and Apert's syndromes with paternal age. In response to DNA damage, multiple overlapping systems of DNA repair have evolved, preferentially repairing the transcribed strand within transcriptionally-active regions of the genome. These include direct reversal of dimers and specific adducts and pathways for base excision, nucleotide excision, and mismatch repair. A consensus has emerged that some DNA repair capacities decline with organism age, contradictory reports notwithstanding. As is the case for inborn defects in humans, knockout mice lacking components of nucleotide excision repair or DNA-damage checkpoint arrest have increased frequencies of skin and internal cancers, whereas mice overexpressing DNA repair genes have fewer spontaneous cancers. Oxidative stress and resultant free radicals can damage genomic and mitochondrial DNA; damage increases with age but decreases with caloric restriction. We review recent studies of long-lived C. elegans mutants which appear to involve metabolic attenuation, the role of telomere shortening and telomerase in cellular senescence, and the genetic bases of progeroid syndromes in humans. Finally, we discuss roles of extrinsic and intrinsic factors in skin aging, and their association with DNA damage, emphasizing preventive and protective measures and prospects for intervention by modulating DNA repair pathways in the skin.
PubMed: 23604396
DOI: 10.1007/s11357-999-0006-3 -
Age (Dordrecht, Netherlands) Dec 2013Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages...
Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages commonly being grouped into a small number of crude ranges reflecting the major stages of development and aging, such as childhood or adolescence. Here, we investigate the possibility of redefining age groups using the recently developed Age-Phenome Knowledge-base (APK) that holds over 35,000 literature-derived entries describing relationships between age and phenotype. Clustering of APK data suggests 13 new, partially overlapping, age groups. The diseases that define these groups suggest that the proposed divisions are biologically meaningful. We further show that the number of different age ranges that should be considered depends on the type of disease being evaluated. This finding was further strengthened by similar results obtained from clinical blood measurement data. The grouping of diseases that share a similar pattern of disease-related reports directly mirrors, in some cases, medical knowledge of disease-age relationships. In other cases, our results may be used to generate new and reasonable hypotheses regarding links between diseases.
Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Aging; Biomedical Research; Child; Child, Preschool; Cluster Analysis; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Models, Statistical; Young Adult
PubMed: 23354682
DOI: 10.1007/s11357-013-9510-6 -
Age Jan 1997During the past 15 years, our aging colony of rhesus monkeys, consisting of animals from 20 to 37 years of age, had an annual average population of 88.2 live monkeys...
During the past 15 years, our aging colony of rhesus monkeys, consisting of animals from 20 to 37 years of age, had an annual average population of 88.2 live monkeys and, of this population, an annual average of 13.9 monkeys died spontaneously or were terminated due to severe illness. From 1980 to 1994, a total of 175 autopsies of rhesus macaques, from 20 to 37 years of age, were performed. By cumulative autopsy data, the incidence of age-related pathology in various organs was surveyed. Major geriatric diseases such as coronary sclerosis, emphysema, degenerative joint disorders, cancer, and cerebral amyloid plaque began to develop in 10 to 40% of macaques after 20 years and the incidence significantly increased after 26 years of age. Approximately 12% of aged macaques from 20 to 30 years of age died annually due to such geriatric diseases with severe complications. The average survival rate indicated that half the population at 20 years of age died by 25 years and 73% died by 30 years of age. Less than 10% of macaques survived over 30 years. Using these aged macaques as well as other juvenile to adult monkeys in our Center, clinical opththalmological and reproductive endocrinological studies, and magnetic resonance imaging (MRI) of the brain were conducted to define bioaging markers of captive rhesus monkeys. Cataracts began to develop in 20% of rhesus monkeys at 20 to 22 years of age and the rate significantly increased after 26 years of age. Menopause occurred at 26 to 27 years of age. Multiple cerebral infarctions and iron deposits in the globus pallidus and substantia nigra were detected by MRI in the aged brains. These geriatric disorders in captive aged macaques appear to be natural aging outcomes, since the simple lifestyle of these captive animals offers minimal exposure to environmental factors. Our data will offer useful paradigms for preventive or experimental studies on age-related diseases.
PubMed: 23604287
DOI: 10.1007/s11357-997-0001-5 -
Age (Dordrecht, Netherlands) Feb 2016Age-related changes in muscle quality and muscle mass in the forearm, which relate to decline in handgrip strength (HGS), have not been reported. The purpose of this...
Age-related changes in muscle quality and muscle mass in the forearm, which relate to decline in handgrip strength (HGS), have not been reported. The purpose of this study was to investigate the relationships between age-related declines in HGS and loss of muscle thickness and/or muscle quality in the forearm of 613 adults (306 men and 307 women) aged 20-89. Anterior forearm muscle thickness (MT-ulna) and HGS were measured using an ultrasound and a hand dynamometer, respectively, in the dominant hand. Muscle quality (fMQ) was defined as a ratio of HGS to MT-ulna. HGS was similar among younger (ages 20-29, 30-39, and 40-49) groups and was progressively lower with increasing age in both sexes. MT-ulna was similar between ages 20-29 and 60-69 in men and between ages 20-29 and 70-79 in women. In men, MT-ulna was lower in ages 70-79 and 80-89 compared with other age groups. In women, MT-ulna was lower in ages 80-89 compared with ages 20-29 and 40-49. In both men and women, fMQ was identical among younger (ages 20-29, 30-39, and 40-49) groups. After that fMQ was progressively lower with age in both men and women. The results indicated that age-related decline in HGS is associated with fMQ, but it appears to be accelerated after the seventh decade due to muscle loss.
Topics: Adult; Aged; Aged, 80 and over; Aging; Anthropometry; Female; Hand Strength; Healthy Volunteers; Humans; Male; Middle Aged; Muscle, Skeletal; Young Adult
PubMed: 26874950
DOI: 10.1007/s11357-016-9891-4 -
Age (Dordrecht, Netherlands) Feb 2016Our study aimed to examine and quantify age-related structural alterations in the healthy mouse bladder using ex vivo two-photon laser scanning microscopy (TPLSM)....
Our study aimed to examine and quantify age-related structural alterations in the healthy mouse bladder using ex vivo two-photon laser scanning microscopy (TPLSM). Freshly dissected bladders from 25-, 52-, and 85-week-old C57bl/6J mice were examined, and morphological analyses and quantification of cell layers and nerves were performed. The numbers of stretched, curled, branched, and total number of nerves in volume units of the stained muscle layer were quantified. We observed differences in the bladder wall architecture and innervation with age. Especially in 85-week-old mice, age-related changes were found, including detachment of urothelial cells and an increase in connective tissue, intermingled with the smooth muscle fibers in the muscle layer (collagen-smooth muscle ratio of 1.15 ± 0.29). In 25- and 52-week-old mice, the collagen-smooth muscle ratios were 0.20 ± 0.04 and 0.31 ± 0.11, respectively, and a clear separation of collagen and muscle was observed. The overall number of nerves and the number of curled nerves were significantly higher in the 85-week-old mice (74.0 ± 13.0 and 25.9 ± 4.8, respectively), when comparing to 25-week-old mice (26.0 ± 2.7 and 6.7 ± 1.2, respectively) and 52-week-old mice (43.8 ± 4.3 and 22.1 ± 3.3, respectively). Significant age-related alterations in bladder morphology and innervation were found, when comparing freshly dissected bladder tissue from 25-, 52-, and 85-week-old mice. The higher number of curled nerves might be an indication of an increased neurotransmitter release, resulting in a higher nerve activity, with a part of the nerves being possibly mechanically impaired. This study shows that two-photon laser scanning microscopy of healthy aging male mice is a useful method to investigate and quantify the age-related changes in the bladder wall.
Topics: Aging; Animals; Male; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence, Multiphoton; Muscle, Smooth; Sensory Receptor Cells; Urinary Bladder
PubMed: 26825637
DOI: 10.1007/s11357-016-9878-1 -
Age (Dordrecht, Netherlands) Aug 2013Cutaneous sensation deteriorates with age. It is not known if this change is consistent over the entire hand or if sensation is affected by changes in skin mechanics.... (Comparative Study)
Comparative Study
Cutaneous sensation deteriorates with age. It is not known if this change is consistent over the entire hand or if sensation is affected by changes in skin mechanics. Cutaneous perceptual thresholds were tested at eight sites in the glabrous skin and two in the hairy skin of both hands in 70 subjects (20-88 years), five male and five female per decade, using calibrated von Frey filaments, two-point discrimination, and texture discrimination. Venous occlusion at the wrist (40 ± 10 mmHg) and moisturizer were used to alter skin mechanics. Cutaneous thresholds increased significantly with age (p < 0.001); von Frey thresholds were 0.04 g [0.02-0.07] (median and interquartile range) in the 20s and 0.16 g [0.04-0.4] in the 80s, with differences between hands for older females (p = 0.044) but not males. The pattern of changes in cutaneous sensation varied according to the site tested with smaller changes on the fingers compared to the palm. Two-point discrimination deteriorated with age (p = 0.046), but with no interaction between sex, handedness, or changes in skin mechanics. There were no significant differences for texture discrimination. Changes in skin mechanics improved cutaneous thresholds in the oldest males after moisturizing (p = 0.001) but not otherwise. These results emphasize the complex pattern of age-related deterioration in cutaneous sensation with differences between sexes, the hands, sites on the hand, and the mode of testing. As the index fingertip is not a sensitive indicator of sensory decline, the minimum assessment of age-related changes in cutaneous sensation should include both hands, and sites on the palm.
Topics: Adult; Aged; Aged, 80 and over; Aging; Female; Follow-Up Studies; Hand; Humans; Male; Middle Aged; Physical Stimulation; Reference Values; Sensation; Sensory Thresholds; Skin; Young Adult
PubMed: 22661298
DOI: 10.1007/s11357-012-9429-3 -
Age (Dordrecht, Netherlands) Jun 2016The aim of this study was to concurrently assess the effect of age on neuromuscular and mechanical properties in 24 young (23.6 ± 3.7 years) and 20 older...
The aim of this study was to concurrently assess the effect of age on neuromuscular and mechanical properties in 24 young (23.6 ± 3.7 years) and 20 older (66.5 ± 3.8 years) healthy males and females. Maximal strength of knee extensors (KE) and flexors (KF), contractile rate of torque development (RTD) and neural activation of agonist-antagonist muscles (surface EMG) were examined during maximal voluntary isometric contraction (MVIC). Tissue stiffness (i.e. musculo-articular stiffness (MAS) and muscle stiffness (MS)) was examined via the free-oscillation technique, whereas muscle architecture (MA) of the vastus lateralis and subcutaneous fat were measured by ultrasonography. Males exhibited a greater age-related decline for KE (47.4 %) and KF (53.1 %) MVIC, and RTD (60.4 %) when compared to females (32.9, 42.6 and 34.0 %, respectively). Neural activation of agonist muscles during KE MVIC falls markedly with ageing; however, no age and sex effects were observed in the antagonist co-activation. MAS and MS were lower in elderly compared with young participants and in females compared with males. Regarding MA, main effects for age (young 23.0 ± 3.3 vs older 19.5 ± 2.0 mm) and sex (males 22.4 ± 3.5 vs females 20.4 ± 2.7 mm) were detected in muscle thickness. For fascicle length, there was an effect of age (young 104.6 ± 8.8 vs older 89.8 ± 10.5 mm), while for pennation angle, there was an effect of sex (males 13.3 ± 2.4 vs females 11.5 ± 1.7°). These findings suggest that both neuromuscular and mechanical declines are important contributors to the age-related loss of muscle strength/function but with some peculiar sex-related differences.
Topics: Adult; Age Factors; Aged; Aging; Biomechanical Phenomena; Electromyography; Female; Humans; Isometric Contraction; Knee Joint; Male; Middle Aged; Muscle Strength; Quadriceps Muscle; Sex Factors; Young Adult
PubMed: 27189591
DOI: 10.1007/s11357-016-9921-2 -
Age (Dordrecht, Netherlands) 2014It is not known whether there are age- and/or gender-related differences in magnitude of motor-evoked potentials (MEPs) of the submental muscles. Knowledge of this is... (Comparative Study)
Comparative Study
It is not known whether there are age- and/or gender-related differences in magnitude of motor-evoked potentials (MEPs) of the submental muscles. Knowledge of this is important in investigations of neurophysiological aspects of swallowing. Forty healthy participants (20 males, 20 females; 20 young [21-35 years], 20 old [53-88 years]) were recruited. Surface electromyography (EMG) electrodes were placed at midline underlying the submental muscle group. Age- and gender-related differences were evaluated in two neurophysiologic measures of swallowing: MEPs stimulated by single-pulse transcranial magnetic stimulation (TMS) over the motor cortex and surface electromyography (sEMG) recorded from the same submental muscle group during non-stimulated swallows. The older participants had larger MEPs during saliva swallowing than the young participants (p = 0.04, d = 0.86). Conversely, the older participants had lower amplitude submental EMG activity during non-stimulated swallows (p = 0.045, d = 0.67). Gender had no significant effect on MEP magnitude and on submental activity during saliva swallowing. There were no effects of age or gender on MEP latencies. These findings suggest deterioration in muscle function with age in a sample of healthy adults presenting with functional swallowing. We speculate that muscular decline is partially ameliorated by increased cortical activity-i.e., increased submental MEPs-so as to preserve swallowing function in healthy older subjects. These findings emphasize the need for different reference points for evaluation of submental MEPs of different age groups.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Cohort Studies; Confidence Intervals; Deglutition; Electrodes, Implanted; Electromyography; Evoked Potentials, Motor; Female; Geriatric Assessment; Humans; Male; Middle Aged; Muscle Contraction; Neck Muscles; Neurophysiology; New Zealand; Palatal Muscles; Prospective Studies; Reference Values; Sex Factors; Transcranial Magnetic Stimulation; Young Adult
PubMed: 25502005
DOI: 10.1007/s11357-014-9735-z -
Age (Dordrecht, Netherlands) Dec 2013Pulse wave velocity (PWV) is an independent predictor of cardiovascular (CV) risk. Higher PWV values have been observed in Africans; however, there are no established...
Pulse wave velocity (PWV) is an independent predictor of cardiovascular (CV) risk. Higher PWV values have been observed in Africans; however, there are no established age- and gender-adjusted reference values for this population. Therefore, PWV was measured using a validated device (Complior SP) in 544 subjects recruited from an occupational cohort of employees of a public university in Angola. Since high blood pressure (BP) is an important factor influencing PWV, a subsample of 301 normotensive subjects (aged 22-72 years) was selected for this study. A subset of 131 individuals without CV risk factors was considered the healthy group (HG), while the entire group (n = 301) comprised the less healthy group (LHG). Predictors of PWV were evaluated using multiple regression analyses and age- and gender-specific percentile tables and curves were constructed. Age and PWV means were 36 ± 9.7 years and 6.6 ± 1.0 m/s in the HG, respectively, and 39.9 ± 10.2 years and 7.3 ± 1.3 m/s in the LHG. Age and plasma uric acid (UA) were the only significant PWV predictors in the HG, while age, mean BP (MBP), and gender showed significant prediction of PWV in the multiple regression analysis in the LHG. Age- and gender-adjusted reference values of PWV were provided for healthy and less healthy normotensive Africans. Considering the small sample size of our cohort, these preliminary results should be used cautiously until data on robust sample of the general population can be obtained.
Topics: Adult; Age Factors; Aged; Aging; Angola; Blood Flow Velocity; Cardiovascular Diseases; Cross-Sectional Studies; Female; Humans; Incidence; Male; Middle Aged; Prognosis; Pulse Wave Analysis; Reference Values; Risk Factors; Sex Factors; Young Adult
PubMed: 23319362
DOI: 10.1007/s11357-012-9504-9 -
Age (Dordrecht, Netherlands) Feb 2015Similarity in oldest parturitions in humans and great apes suggests that we maintain ancestral rates of ovarian aging. Consistent with that hypothesis, previous counts... (Comparative Study)
Comparative Study
Similarity in oldest parturitions in humans and great apes suggests that we maintain ancestral rates of ovarian aging. Consistent with that hypothesis, previous counts of primordial follicles in postmortem ovarian sections from chimpanzees (Pan troglodytes) showed follicle stock decline at the same rate that human stocks decline across the same ages. Here, we correct that finding with a chimpanzee sample more than three times larger than the previous one, which also allows comparison into older ages. Analyses show depletion rates similar until about age 35, but after 35, the human counts continue to fall with age, while the change is much less steep in chimpanzees. This difference implicates likely effects on ovarian dynamics from other physiological systems that are senescing at different rates, and, potentially, different perimenopausal experience for chimpanzees and humans.
Topics: Adolescent; Adult; Aging; Animals; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Middle Aged; Ovarian Follicle; Ovarian Reserve; Pan troglodytes; Young Adult
PubMed: 25651885
DOI: 10.1007/s11357-015-9746-4