Biological Aging and Longevity: Underlying Mechanisms and Potential Intervention Strategies

1994 ◽  
Vol 2 (4) ◽  
pp. 304-328 ◽  
Author(s):  
George T. Baker ◽  
George R. Martin
Keyword(s):  
Life Span ◽  
Genetic Factors ◽  
Physiological Function ◽  
Intervention Strategies ◽  
Biological Aging ◽  
Human Aging ◽  
Experimental Paradigm ◽  
Positive Effects ◽  
Physiological Fitness ◽  
Underlying Mechanisms

Aging is characterized by numerous physical, physiological, biochemical, and molecular changes. The rates at which aging processes occur are highly variable among individuals and are thought to be governed by both environmental and genetic factors. Lifestyle factors such as exercise, dietary, and smoking habits have been demonstrated to alter many of the changes usually associated with human aging. However, at present caloric restriction is the only experimental paradigm that has consistently been demonstrated in animal models to extend not only physiological vigor but also life span. The positive effects of exercise on physiological fitness and the reduction in the risks of certain diseases have been well documented. However, its effects on life span are not as clear. This article explores some of the basic mechanisms thought to be involved causally in the processes of aging, and outlines current and potential interventive strategies to retard or ameliorate the rates of decline in physiological function with advancing age.

Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework

2019 ◽  
Author(s):  
Juyoen Hur ◽  
Melissa D. Stockbridge ◽  
Andrew S. Fox ◽  
Alexander J. Shackman
Keyword(s):  
Risk Factor ◽  
Anxiety Disorders ◽  
Executive Control ◽  
Intervention Strategies ◽  
Attentional Biases ◽  
Translational Neuroscience ◽  
Adult Personality ◽  
Fundamental Dimension ◽  
To Come ◽  
Underlying Mechanisms

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the underlying mechanisms have only recently begun to come into focus. Here, we review new insights into the nature and biological bases of dispositional negativity, a fundamental dimension of childhood temperament and adult personality and a prominent risk factor for the development of pediatric and adult anxiety disorders. Converging lines of epidemiological, neurobiological, and mechanistic evidence suggest that dispositional negativity increases the likelihood of psychopathology via specific neurocognitive mechanisms, including attentional biases to threat and deficits in executive control. Collectively, these observations provide an integrative translational framework for understanding the development and maintenance of anxiety disorders in adults and youth and set the stage for developing improved intervention strategies.

scholarly journals Traits that influence longevity in mice: a second look.

Genetics ◽  
1992 ◽  
Vol 132 (1) ◽  
pp. 229-239
Author(s):  
K B Dear ◽  
M Salazar ◽  
A L Watson ◽  
R S Gelman ◽  
R Bronson ◽  
...  
Keyword(s):  
Life Span ◽  
Genetic Factors ◽  
Viral Infections ◽  
Genetic Interactions ◽  
Chromosome 9 ◽  
Chromosome 4 ◽  
Histological Findings ◽  
Male And Female ◽  
Female Genotype ◽  
Dominant Black

Abstract Analysis of genetic interactions in the F2 of an intercross of (C57BL/6 x DBA/2) F1J revealed influences of genetic factors on life span. Females lived longer than males. Dilute brown females died sooner than females of other colors. H-2b/H-2b males died sooner than H-2b/H-2d or H-2d/H-2d males, except that among dilute brown males those of typeH-2b/H-2d died sooner. Cluster analysis suggested that male and female genotypes each fall into two groups, with female dilute brown mice having shorter lives than other females, and male H-2b/H-2b mice except dilute brown and dilute brown H-2b/H-2d mice having shorter lives than other males. The association of heterozygosity with life span was clearer in females than in males, yet the longest-lived female genotype was homozygous H-2d/H-2d, of dominant Black phenotype at the Brown locus of chromosome 4, and homozygous dd at the Dilute locus of chromosome 9. The shortest-lived females were dilute brown H-2b/H-2b. The longest-lived and shortest-lived male genotypes were dilute brown H-2d/H-2d and dilute brown H-2b/H-2d, respectively. Although histological findings at postmortem differed between the sexes, there was no association of particular disorders with other genetic markers. The importance of H-2 in males was confirmed, but the allelic effects were perturbed, possibly by the absence of Sendai infection in this experiment. Overall our studies suggest that genetic influences on life span involve interactions between loci, and allelic interactions may change with viral infections or other environmental factors.

scholarly journals Deficiency in Poly(ADP-ribose) Polymerase-1 (PARP-1) Accelerates Aging and Spontaneous Carcinogenesis in Mice

2008 ◽  
Vol 2008 ◽  
pp. 1-11 ◽  
Author(s):  
Tatiana S. Piskunova ◽  
Maria N. Yurova ◽  
Anton I. Ovsyannikov ◽  
Anna V. Semenchenko ◽  
Mark A. Zabezhinski ◽  
...  
Keyword(s):  
Dna Repair ◽  
Life Span ◽  
Soft Tissues ◽  
Telomere Maintenance ◽  
Biological Aging ◽  
Spontaneous Tumors ◽  
Uterine Tumors ◽  
Dna Repair Gene ◽  
Spontaneous Carcinogenesis ◽  
Parp 1

Genetic and biochemical studies have shown that PARP-1 and poly(ADP-ribosyl)ation play an important role in DNA repair, genomic stability, cell death, inflammation, telomere maintenance, and suppressing tumorigenesis, suggesting that the homeostasis of poly(ADP-ribosyl)ation and PARP-1 may also play an important role in aging. Here we show that PARP- mice exhibit a reduction of life span and a significant increase of population aging rate. Analysis of noninvasive parameters, including body weight gain, body temperature, estrous function, behavior, and a number of biochemical indices suggests the acceleration of biological aging in PARP- mice. The incidence of spontaneous tumors in both PARP- and PARP- groups is similar; however, malignant tumors including uterine tumors, lung adenocarcinomas and hepatocellular carcinomas, develop at a significantly higher frequency in PARP- mice than PARP- mice (72% and 49%, resp.; .05). In addition, spontaneous tumors appear earlier in PARP- mice compared to the wild type group. Histopathological studies revealed a wide spectrum of tumors in uterus, ovaries, liver, lungs, mammary gland, soft tissues, and lymphoid organs in both groups of the mice. These results demonstrate that inactivation of DNA repair gene PARP-1 in mice leads to acceleration of aging, shortened life span, and increased spontaneous carcinogenesis.

Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention

2007 ◽  
Vol 32 (5) ◽  
pp. 954-966 ◽  
Author(s):  
Christy S. Carter ◽  
Tim Hofer ◽  
Arnold Y. Seo ◽  
Christian Leeuwenburgh
Keyword(s):  
Life Span ◽  
Calorie Restriction ◽  
Aging Process ◽  
Molecular Mechanisms ◽  
Geriatric Medicine ◽  
Functional Decline ◽  
Intervention Strategies ◽  
Health Span ◽  
Structural Deterioration ◽  
Age Related

The aging process results in a gradual and progressive structural deterioration of biomolecular and cellular compartments and is associated with many pathological conditions, including cardiovascular disease, stroke, Alzheimer’s disease, osteoporosis, sarcopenia, and liver dysfunction. Concomitantly, each of these conditions is associated with progressive functional decline, loss of independence, and ultimately disability. Because disabled individuals require care in outpatient or home care settings, and in light of the social, emotional, and fiscal burden associated with caring for an ever-increasing elderly population, research in geriatric medicine has recently focused on the biological mechanisms that are involved in the progression towards functional decline and disability to better design treatment and intervention strategies. Although not completely understood, the mechanisms underlying the aging process may partly involve inflammatory processes, oxidative damage, mitochondrial dysfunction, and apoptotic tissue degeneration. These hypotheses are based on epidemiological evidence and data from animal models of aging, as well as interventional studies. Findings from these studies have identified possible strategies to decrease the incidence of age-related diseases and delay the aging process. For example, lifelong exercise is known to extend mean life-span, whereas calorie restriction (CR) increases both mean and maximum life-span in a variety of species. Optimal application of these intervention strategies in the elderly may positively affect health-related outcomes and possibly longevity. Therefore, the scope of this article is to (i) provide an interpretation of various theories of aging from a “health-span” perspective; (ii) describe interventional testing in animals (CR and exercise); and (iii) provide a translational interpretation of these data.

Bridging employee curiosity and service creativity: a new lens

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Kuen-Hung Tsai ◽  
Li-li Zheng
Keyword(s):  
Knowledge Sharing ◽  
Service Firms ◽  
Frontline Employees ◽  
Content Type ◽  
Main Research ◽  
Positive Effects ◽  
Task Autonomy ◽  
Different Types ◽  
Underlying Mechanisms ◽  
And Task

PurposeThis study develops a framework to examine how, why and when different traits of employee curiosity affect service creativity by considering the roles of knowledge sharing and task autonomy.Design/methodology/approachTo reduce common method bias, this work separated the variables investigated into three parts, each of which was randomly used to collect data at three different periods. A total of 822 matched questionnaires obtained from frontline employees of service firms provided useable data for hypothesis tests. A moderated mediation approach was employed to analyse the data.FindingsResults are as follows: (1) Deprivation sensitivity, joyous exploration and social curiosity have positive effects on knowledge collecting (KC) and knowledge donating (KD). (2) KD mediates the relationships between the three curiosity traits and service creativity. (3) Task autonomy enhances and suppresses the mediating effects of KC and KD, respectively, on the curiosity–service creativity relationship.Research limitations/implicationsThis study has two main research implications: First, as different types (traits) of employee curiosity have different effects on service creativity, a single-dimensional view of employee curiosity may mask the differences of individual dimension and lead to a oversimplified conclusion. Second, lifting the vein from employee curiosity to service creativity has to consider the roles of knowledge sharing and task autonomy.Originality/valueThis research is the first to contribute to the service innovation literature by revealing the underlying mechanisms through which different types of employee curiosity affect service creativity and uncovering the moderating roles of task autonomy in the process mechanisms.

How vendor capabilities impact IT outsourcing performance

2019 ◽  
Vol 32 (2) ◽  
pp. 325-344 ◽  
Author(s):  
Meng-Meng Wang ◽  
Jian-Jun Wang
Keyword(s):  
Indirect Effect ◽  
Least Squares Method ◽  
It Outsourcing ◽  
Learning Capability ◽  
Content Type ◽  
Positive Effects ◽  
Moderated Mediation Model ◽  
Underlying Mechanisms ◽  
Internal Integration ◽  
Partial Least Squares Method

Purpose The purpose of this paper is to explore the underlying mechanisms through which integration capability and learning capability influence IT outsourcing performance from vendor’s perspective. Design/methodology/approach This paper develops a moderated mediation model to explain the underlying influence processes of integration capability and learning capability on vendor’s performance. A sample of 237 vendor firms was obtained from China through two separated surveys. The hypotheses were tested with the partial least squares method and bias-corrected bootstrapping method. Findings The empirical results indicate that external integration capability (EIC) mediates the effect of internal integration capability (IIC) on vendor outsourcing performance, and the relationship between EIC and vendor performance is positively moderated by learning capability, while learning capability has a negative moderating effect on the link between IIC and vendor performance. Further, the conditional indirect effect is suggested. The indirect effect of IIC on vendor performance through EIC becomes non-significant when learning capability is low. Originality/value This study highlights the counterintuitive notion that learning capability may not always have uniformly positive effects and figure out the mechanism through which integration capability and learning capability can effectively improve IT outsourcing performance.

scholarly journals Identifying Characteristics of Frailty in Female Mice Using a Phenotype Assessment Tool

2019 ◽  
Vol 75 (4) ◽  
pp. 640-646 ◽  
Author(s):  
Dongmin Kwak ◽  
Cory W Baumann ◽  
LaDora V Thompson
Keyword(s):  
Physical Activity ◽  
Body Weight ◽  
Life Span ◽  
Walking Speed ◽  
Assessment Tool ◽  
Preclinical Studies ◽  
Frailty Phenotype ◽  
Female Mice ◽  
Yield Information ◽  
Underlying Mechanisms

Abstract Preclinical studies are important in identifying the underlying mechanisms contributing to frailty. Frailty studies have mainly focused on male rodents with little directed at female rodents. Therefore, the purposes of this study were to identify the onset and prevalence of frailty across the life span in female mice, and to determine if frailty predicts mortality. Female C57BL/6 (n = 27) mice starting at 17 months of age were assessed across the life span using a frailty phenotype, which included body weight, walking speed, strength, endurance, and physical activity. The onset of frailty occurred at approximately 17 months (1/27 mice), with the prevalence of frailty increasing thereafter. At 17 months, 11.1% of the mice were pre-frail and by 26 months peaked at 36.9%. The percentage of frail mice progressively increased up to 66.7% at 32 months. Non-frail mice lived to 29 months whereas frail/pre-frail mice lived only to 26 months (p = .04). In closing, using a mouse frailty phenotype, we are able to identify that the prevalence of frailty in female mice increases across the life span and accurately predicts mortality. Together, this frailty phenotype has the potential to yield information about the underlying mechanisms contributing to frailty.

scholarly journals Education and Cognitive Functioning Across the Life Span

2020 ◽  
Vol 21 (1) ◽  
pp. 6-41 ◽  
Author(s):  
Martin Lövdén ◽  
Laura Fratiglioni ◽  
M. Maria Glymour ◽  
Ulman Lindenberger ◽  
Elliot M. Tucker-Drob
Keyword(s):  
Cognitive Function ◽  
Educational Attainment ◽  
Cognitive Decline ◽  
Life Span ◽  
Cognitive Ability ◽  
Cognitive Abilities ◽  
Cognitive Aging ◽  
Early Adulthood ◽  
Late Life ◽  
Positive Effects

Cognitive abilities are important predictors of educational and occupational performance, socioeconomic attainment, health, and longevity. Declines in cognitive abilities are linked to impairments in older adults’ everyday functions, but people differ from one another in their rates of cognitive decline over the course of adulthood and old age. Hence, identifying factors that protect against compromised late-life cognition is of great societal interest. The number of years of formal education completed by individuals is positively correlated with their cognitive function throughout adulthood and predicts lower risk of dementia late in life. These observations have led to the propositions that prolonging education might (a) affect cognitive ability and (b) attenuate aging-associated declines in cognition. We evaluate these propositions by reviewing the literature on educational attainment and cognitive aging, including recent analyses of data harmonized across multiple longitudinal cohort studies and related meta-analyses. In line with the first proposition, the evidence indicates that educational attainment has positive effects on cognitive function. We also find evidence that cognitive abilities are associated with selection into longer durations of education and that there are common factors (e.g., parental socioeconomic resources) that affect both educational attainment and cognitive development. There is likely reciprocal interplay among these factors, and among cognitive abilities, during development. Education–cognitive ability associations are apparent across the entire adult life span and across the full range of education levels, including (to some degree) tertiary education. However, contrary to the second proposition, we find that associations between education and aging-associated cognitive declines are negligible and that a threshold model of dementia can account for the association between educational attainment and late-life dementia risk. We conclude that educational attainment exerts its influences on late-life cognitive function primarily by contributing to individual differences in cognitive skills that emerge in early adulthood but persist into older age. We also note that the widespread absence of educational influences on rates of cognitive decline puts constraints on theoretical notions of cognitive aging, such as the concepts of cognitive reserve and brain maintenance. Improving the conditions that shape development during the first decades of life carries great potential for improving cognitive ability in early adulthood and for reducing public-health burdens related to cognitive aging and dementia.

scholarly journals Are masters athletic performances predictive of human aging in men and women?

2019 ◽  
pp. 5-12 ◽  
Author(s):  
Jonathon W. Senefeld ◽  
Sandra K. Hunter
Keyword(s):  
Physical Activity ◽  
Athletic Performance ◽  
Age Groups ◽  
Biological Aging ◽  
Human Aging ◽  
Healthy Human ◽  
Cross Sectional ◽  
Very Old ◽  
Age Related ◽  
Human Function

Human aging particularly after ∼70 years, is associated with declines in physical function and athletic performance, that are accelerated in part by age-associated declines in physical activity and exercise training. Because elite athletes maintain high levels of physical activity across the lifespan, older athletes (Masters) may present as a proxy for healthy human aging. Although longitudinal studies are most informative about human aging, there are substantial practical challenges to conducting longitudinally designed research. Masters athletic records and comparisons of performance across age groups can serve as a practical and unique probe to predict the trajectory of human function throughout the lifespan. While useful, the cross-sectional comparison of elite athletic performance across different age groups, however, has inherent limitations in predicting healthy human aging, particularly among women. This review presents evidence that (1) there is a progressive age-related decline in world class performances in freestyle swim swimming, marathon, and triathlon, that accelerates into very old age (∼70 years), and (2) lower participation rates of women relative to men results in an overestimation of the age-related decline in athletic performance particularly in very old women. Thus, while useful, there are some limitations to predicting biological aging among women using current Masters Athletic performances.

scholarly journals Sex/Gender-Specific Imbalance in CVD: Could Physical Activity Help to Improve Clinical Outcome Targeting CVD Molecular Mechanisms in Women?

2020 ◽  
Vol 21 (4) ◽  
pp. 1477
Author(s):  
Mauro Vaccarezza ◽  
Veronica Papa ◽  
Daniela Milani ◽  
Arianna Gonelli ◽  
Paola Secchiero ◽  
...  
Keyword(s):  
Physical Activity ◽  
Molecular Mechanisms ◽  
Population Aging ◽  
Sex And Gender ◽  
Cvd Risk ◽  
Men And Women ◽  
Positive Effects ◽  
And Gender ◽  
Underlying Mechanisms ◽  
Gender Specific

In the last two decades, new insights have been gained regarding sex/gender-related differences in cardiovascular disease (CVD). CVD represents the leading cause of death worldwide in both men and women, accounting for at least one-third of all deaths in women and half of deaths in women over 50 years in developing countries. Important sex-related differences in prevalence, presentation, management, and outcomes of different CVDs have been recently discovered, demonstrating sex/gender-specific pathophysiologic features in the presentation and prognosis of CVD in men and women. A large amount of evidence has highlighted the role of sex hormones in protecting women from CVDs, providing an advantage over men that is lost when women reach the menopause stage. This hormonal-dependent shift of sex-related CVD risk consequently affects the overall CVD epidemiology, particularly in light of the increasing trend of population aging. The benefits of physical activity have been recognized for a long time as a powerful preventive approach for both CVD prevention and aging-related morbidity control. Exercise training is indeed a potent physiological stimulus, which reduces primary and secondary cardiovascular events. However, the underlying mechanisms of these positive effects, including from a sex/gender perspective, still need to be fully elucidated. The aim of this work is to provide a review of the evidence linking sex/gender-related differences in CVD, including sex/gender-specific molecular mediators, to explore whether sex- and gender-tailored physical activity may be used as an effective tool to prevent CVD and improve clinical outcomes in women.

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