Cellular theory of aging states that human aging is the result of cellular aging, in which an increasing proportion of cells reach senescence. Senescence, from the Latin word senex, means "growing old," is an irreversible growth arrest which occurs in response to damaging stimuli, such as DNA damage, telomere shortening, telomere dysfunction and oncogenic stress leading to suppression of potentially dysfunctional, transformed, or aged cells. Cellular senescence is characterized by irreversible cell cycle arrest, flattened and enlarged morphology, resistance to apoptosis, alteration in gene expression and chromatin structure, expression of senescence associated- β-galactosidase (SA-β-gal) and acquisition of senescence associated secretory phenotype (SASP). In this review paper, different types of cellular senescence including replicative senescence (RS) which occurs due to telomere shortening and stress induced premature senescence (SIPS) which occurs in response to different types of stress in cells, are discussed. Biomarkers of cellular senescence and senescent assays including BrdU incorporation assay, senescence associated- β-galactosidase (SA-β-gal) and senescence-associated heterochromatin foci assays to detect senescent cells are also addressed.
The steady decline of physiological function and increased vulnerability to age-related disorders are two features of the complicated biological process of ageing. As a key organ for nutrient absorption, metabolism, and immunological regulation, the gut plays a major part in the ageing process. Drosophila melanogaster, a well-established model organism, has emerged as a significant tool for exploring the intricate rapport between the gut and ageing. Through the use of Drosophila models, the physiological and molecular elements of the gut-brain axis have been thoroughly explored. These models have also provided insights into the mechanisms by which gut health impacts ageing and age-related illnesses. Drosophila's gut microbiota experience dysbiosis with age which has been linked to age-related diseases. To prevent this and promote healthy ageing in Drosophila, gut microbiota modification methods, such as dietary restriction in tandem with time-restricted feeding, administration of pro-, pre- and synbiotics, as well as pharmaceutical interventions have been generated with positive impacts. The article also covers the drawbacks and difficulties of investigating the gut via the Drosophila. Thus, with an emphasis on the lessons discovered from Drosophila research, this review provides an extensive description of the current studies on the role of the gut-brain axis in ageing and health.
To facilitate the process of aging healthily and prevent age-related health problems, efforts to properly understand aging mechanisms and develop effective and affordable anti-aging interventions are deemed necessary. Systemic administration of D-galactose has been established to artificially induce senescence in vitro and in vivo as well as for anti-aging therapeutic interventions studies. The aim of this article is to comprehensively discuss the use of D-galactose to generate a model of accelerated aging and its possible underlying mechanisms involved in different tissues/organs.
Senescence and autophagy play important roles in homeostasis. Cellular senescence and autophagy commonly cause several degenerative processes, including oxidative stress, DNA damage, telomere shortening, and oncogenic stress; hence, both events are known to be interrelated. Autophagy is well known for its disruptive effect on human diseases, and it is currently proposed to have a direct effect on triggering senescence and quiescence. However, it is yet to be proven whether autophagy has a positive or negative impact on senescence. It is known that elevated levels of autophagy induce cell death, whereas inadequate autophagy can trigger cellular senescence. Both have important roles in human diseases such as aging, renal degeneration, neurodegenerative disorders, and cancer. Therefore, this review aims to highlight the relevance of senescence and autophagy in selected human ailments through a summary of recent findings on the connection and effects of autophagy and senescence in these diseases.
PURPOSE: The proposed Men's Health Index (MHI) aims to provide a practical and systematic framework for comprehensively assessing and stratifying older men with the intention of optimising their health and functional status.
MATERIALS AND METHODS: A literature search was conducted using PubMed from 1980 to 2012. We specifically looked for instruments which: assess men's health, frailty and fitness; predict life expectancy, mortality and morbidities. The instruments were assessed by the researchers who then agreed on the tools to be included in the MHI. When there was disagreements, the researchers discussed and reached a consensus guided by the principle that the MHI could be used in the primary care setting targetting men aged 55-65 years.
RESULTS: The instruments chosen include the Charlson's Combined Comorbidity-Age Index; the International Index of Erectile Function-5; the International Prostate Symptom Score; the Androgen Deficiency in Aging Male; the Survey of Health, Ageing and Retirement in Europe Frailty Instrument; the Sitting-Rising Test; the Senior Fitness Test; the Fitness Assessment Score; and the Depression Anxiety Stress Scale-21. A pilot test on eight men was carried out and showed that the men's health index is viable.
CONCLUSIONS: The concept of assessing, stratifying, and optimizing men's health should be incorporated into routine health care, and this can be implemented by using the MHI. This index is particularly useful to primary care physicians who are in a strategic position to engage men at the peri-retirement age in a conversation about their life goals based on their current and predicted health status.
KEYWORDS: Health status indicators; Men; Physical fitness; Retirement
Visual impairment among the elderly is a major health problem. With advancing age, the normal function of eye tissues decreases and there is an increased incidence of ocular pathology. Demographic studies have shown that age is the best predictor of blindness and visual impairment. The most common causes of age related visual impairment in the elderly are presbyopia, cataracts, age related macular degeneration, primary open angle glaucoma and diabetic retinopathy. Untreated visual impairment leads to physical handicap, increased incidence of fall, depression, social isolation and dependency. Active screening for visual loss in the elderly should be part of the health examination. The elderly should be encouraged to come for formal 1-2 yearly eye assessment for early detection of visual impairment and to treat all associated problems in order to prevent permanent visual loss.
Spirometry was performed on 614 female subjects ranging in age from 13 to 69 years and comprising all the main races in Malaysia. They were divided into six age categories. Mean forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were 2.51 +/- 0.02 and 2.31 +/- 0.02l, respectively. Both FVC and FEV1 correlated negatively with age. Regression analysis revealed an age-related decline in FVC of 220 ml per decade of life. Multiple stepwise regression of the data for the prediction of an individual's FVC above the age of 20 years gave an equation: FVC(l) = 0.0312 (height)-0.022 (age)-1.64. Predicted FVC values derived from equations based on other populations were considerably higher than the observed mean in this study. Our study, therefore, reemphasizes the need to be cautious when applying formulae derived from one population to another. Grossly erroneous conclusions may be reached unless predicted equations for lung-function tests for a given population group are derived from studies based on the same population group.
A trial was conducted to determine the influence of short-term exposure to high ambient temperature at 28 and 35 days of age on deep body temperatures (Tb) and subsequent growth of birds until 42 days of age. A total of 90 day old chicks were reared in stainless steel battery cages and were assigned at random into 18 pens of 5 birds each, with 9 pens containing males and another 9 pens containing females. Three treatment groups, each represented by 3 male and 3 female pens, were represented by T1 without any heat exposure, T2 with heat exposure starting at day 28 and T3 with heat exposure starting at day 35. Heat stress was defined as 180 min exposure to 35 +/- 1 degrees C. Tb and body weights were measured at 35, 37 and 39 days of age immediately following heat exposure. Heat stress resulted in higher Tb and Onset of heat stress at 28 days resulted in significantly lower Tb than onset of heat stress at 35 days. Lower Tb in T2 than T3 permitted recovery in body weight at 42 days. Sexes responded similarly to heat stress.
Riparian ecosystems are amongst the most biodiverse tropical habitats. They are important, and essential, ecological corridors, linking remnant forest fragments. In this study, we hypothesised that crocodile's actively select nocturnal resting locations based on increased macaque predation potential. We examined the importance of riparian vegetation structure in the maintenance of crocodile hunting behaviours. Using airborne Light Detection and Ranging (LiDAR) and GPS telemetry on animal movement, we identified the repeated use of nocturnal resting sites by adult estuarine crocodiles (Crocodylus porosus) throughout the fragmented Lower Kinabatangan Wildlife Sanctuary in Sabah, Malaysia. Crocodile resting locations were found to resemble, in terms of habitat characteristics, the sleeping sites of long-tailed macaque; positioned in an attempt to avoid predation by terrestrial predators. We found individual crocodiles were actively selecting overhanging vegetation and that the protrusion of trees from the tree line was key to site selection by crocodiles, as well as influencing both the presence and group size of sleeping macaques. Although these findings are correlational, they have broad management implications, with the suggestion that riparian corridor maintenance and quality can have implications beyond that of terrestrial fauna. We further place our findings in the context of the wider ecosystem and the maintenance of trophic interactions, and discuss how future habitat management has the potential to mitigate human-wildlife conflict.
PURPOSE: To investigate the relationship between tear ferning patterns (TFP) and non-invasive tear break-up time (NIBUT) in normal Asian subjects.
METHODS: One hundred and forty-five adults with no ocular surface disorders were recruited. TFP and NIBUT were determined. Tears were collected using a capillary tube and allowed to air dry at room temperature for 10min. TFP was later observed using a light microscope and classified according to Rolando's classification. Measurement for NIBUT was obtained using a Tearscope with the slit lamp magnification.
RESULTS: It was found that there is no significant difference between gender in TFP (Z=-1.77, P>.05) and NIBUT (Z=-1.475, P>.05). There is also no significant difference between Malay, Chinese, Indian, and other races in TFP, (H(3)=4.85, P>.05) and NIBUT (H(3)=2.18, P>.05). However, there is a significant difference between age groups of 20-29, 30-39, 40-49,and 50-60 years old in both TFP (H(3)=28.25, P
In the present study, brain activation associated with speech perception processing was examined across four groups of adult participants with age ranges between 20 and 65 years, using functional MRI (fMRI). Cognitive performance demonstrates that performance accuracy declines with age. fMRI results reveal that all four groups of participants activated the same brain areas. The same brain activation pattern was found in all activated areas (except for the right superior temporal gyrus and right middle temporal gyrus); brain activity was increased from group 1 (20-29 years) to group 2 (30-39 years). However, it decreased in group 3 (40-49 years) with further decreases in group 4 participants (50-65 years). Result also reveals that three brain areas (superior temporal gyrus, Heschl's gyrus and cerebellum) showed changes in brain laterality in the older participants, akin to a shift from left-lateralized to right-lateralized activity. The onset of this change was different across brain areas. Based on these findings we suggest that, whereas all four groups of participants used the same areas in processing, the engagement and recruitment of those areas differ with age as the brain grows older. Findings are discussed in the context of corroborating evidence of neural changes with age.
OBJECTIVE: Variations in testosterone levels are associated with several outcomes of aging. The present study aimed to examine the relationship between age-related decline of testosterone levels and changes in bone health status, handgrip strength, body fat percentage and fat-free mass.
MATERIALS AND METHODS: A total of 335 Malaysian Chinese and Malay men aged 40 years and above were recruited for this study. Their body compositions, calcaneal speed of sound and handgrip strength were measured and their blood was collected. Linear regression analysis was done to examine the relationship among age, testosterone levels and outcomes of aging.
RESULTS: The results indicated significant changes in all testosterone measurements, sex hormone binding globulin level, calcaneal speed of sound, handgrip strength, body fat percentage and fat-free mass with age (p < 0.05). Age-dependent decline in bioavailable and free testosterone levels were significantly associated with reduction in calcaneal speed of sound, fat-free mass and handgrip strength (p < 0.05). Age-dependent decline in the total testosterone level was significantly associated with an increase in body fat percentage among the elderly men (p < 0.05).
CONCLUSION: Testosterone levels are associated with changes in outcome of aging such as bone health status, muscle strength and body composition, and the relationships are age-dependent.
We evaluated the possible influence of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) genes on genetic damage due to occupational exposure, which contributes to accelerate ageing. This study was conducted on 120 car auto repair workshop workers exposed to occupational hazards and 120 controls without this kind of exposure. The null and non-null genotypes of GSTM1 and GSTT1 genes were determined by multiplex PCR. Micronucleus frequency, Comet tail length and relative telomere length differences between the null and non-null genotypes of the GSTM1 gene were significantly greater in the exposed group. Lack of GSTT1 did not affect the damage biomarkers significantly (P > 0.05), while lack of GSTM1 was associated with greater susceptibility to genomic damage due to occupational exposure. It was concluded that early ageing is under the influence of these genes and the environmental and socio-demographic factors. Duration of working time was significantly associated with micronucleus frequency, Comet tail length and relative telomere length.
Successful aging is an important and worldwide concept in gerontology. However, until recently, there has been very little known about successful aging in Malaysia. This study was designed to describe the prevalence and correlates of successful aging among older Malaysians.
This study assessed the effects of age and working memory capacity on dichotic listening and temporal sequencing. Double Dichotic Digit Test (DDT), Pitch Pattern Sequence Test (PPST) and Digit Span Test were administered on 40 healthy adults with hearing thresholds of not greater than 30 dB HL across octave frequencies from 250 to 4000 Hz. Twenty young (20-30 years old) and 20 older (50-65 years old) adults were included in the study. Results showed that the older group had significantly lower scores in DDT, PPST and working memory capacity measures than the young subjects. Working memory capacity was positively correlated with PPST but not with DDT, suggesting that DDT might be more auditory-modality-specific than PPST.
Previous studies suggested telomerase activity as a determinant of cell replicative capacity by delaying cell senescence. This study aimed to evaluate the feasibility of adopting telomerase activity as a selection criterion for in vitro expanded skin cells before autologous transplantation. Fibroblasts and keratinoctyes were derived from the same consenting patients aged 9-69 years, and cultured separately in serum-supplemented and serum-free media, respectively. Telomerase activity of fresh and cultured cells were measured and correlated with cell growth rate, donor age and passage number. The results showed that telomerase activity and cell growth were independent of donor age for both cell types. Telomerase was expressed in freshly digested epidermis and dermis and continued expressing in vitro. Keratinocytes consistently showed 3-12 folds greater telomerase activity than fibroblast both in vivo and in vitro. Conversely, growth rate for fibroblast exceeded that of keratinocyte. Telomerase activity decreased markedly at Passage 6 for keratinocytes and ceased by Passage 3 for fibroblasts. The decrease or cessation of telomerase activity coincided with senescence for keratinocyte but not for fibroblast, implying a telomerase-regulated cell senescence for the former and hence a predictor of replicative capacity for this cell type. Relative telomerase activity for fibroblasts from the younger age group was significantly higher than that from the older age group; 69.7% higher for fresh isolates and 31.1% higher at P0 (p<0.05). No detectable telomerase activity was to be found at later subcultures for both age groups. Similarly for keratinocytes, telomerase activity in the younger age group was significantly higher (p<0.05) compared to that in the older age group; 507.7% at P0, 36.8% at P3 and the difference was no longer significant at P6. In conclusion, the study provided evidence that telomerase sustained the proliferation of keratinocytes but not fibroblasts. Telomerase activity is an important criterion for continued survival and replication of keratinocytes, hence its positive detection before transplantation is desirable. Inferring from our results, the use of keratinocytes from Passage 3 or lesser for construction of skin substitute or cell-based therapy is recommended owing to their sustained telomerase expression.