Translational Geroscience: Human Models of Healthy Aging and Longevity

Abstract While insulin like growth factor-1 (IGF-1) is a well-established modulator of aging and longevity in model organisms, its role in humans is less well understood. Previous ambiguities in part have been attributed to cohort characteristics and unawareness of interactions between age and IGF-1. Centenarians have emerged as an ideal model of healthy aging because they delay the onset of age-related diseases and often remain disease free for the duration of their lifespan. In cohorts of centenarians and generally healthy older adults, we demonstrated that reduced IGF-1 is associated with extended lifespan and health-span. Additionally, we confirmed that IGF-1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy: younger individuals with high IGF-1 are protected from dementia, vascular disease, diabetes, cancer, and osteoporosis, while older individuals do not exhibit IGF-1-associated protection from disease. These findings offer evidence for IGF-1 modulating health-span and lifespan in humans.

Download Full-text

Fasting concentrations and postprandial response of 1,2-dicarbonyl compounds 3-deoxyglucosone, glyoxal and methylglyoxal are not increased in healthy older adults

The Journals of Gerontology Series A ◽

10.1093/gerona/glab331 ◽

2021 ◽

Author(s):

Catrin Herpich ◽

Bastian Kochlik ◽

Daniela Weber ◽

Christiane Ott ◽

Tilman Grune ◽

...

Keyword(s):

Age Differences ◽

Healthy Aging ◽

Serum Glucose ◽

Older Individuals ◽

Dicarbonyl Compounds ◽

Healthy Older Adults ◽

Younger Women ◽

Age Related ◽

Postprandial Response ◽

Markers Of Oxidative Stress

Abstract Dicarbonyl stress describes the increased formation of 1,2-dicarbonyl compounds and is associated with age-related pathologies. The role of dicarbonyl stress in healthy aging is poorly understood. In a preliminary study, we analyzed 1,2-dicarbonyl compounds, namely 3-deoxyglucosone (3-DG), glyoxal (GO) and methylglyoxal (MGO) in plasma of older (25 months, n=11) and younger (5 months, n=14) male C57BL/6J (B6) mice via UPLC-MS/MS. Postprandial 3-DG was higher in younger compared to older mice, whereas no differences were found for GO and MGO. Subsequently, in the main study, we analyzed fasting serum of older (OW, 72.4±6.14 years, n=19) and younger women (YW, 27.0±4.42 years, n=19) as well as older (OM, 74.3±5.20 years, n=15) and younger (YM, 27.0±3.34, n=15) men. Serum glucose, insulin, 1,2-dicarbonyl concentrations and markers of oxidative stress were quantified. In a subgroup of this cohort, an oral dextrose challenge was performed and postprandial response of 1,2-dicarbonyl compounds, glucose and insulin were measured. In women, there were no age differences regarding fasting 1,2-dicarbonyl concentrations nor the response after the oral dextrose challenge. In men, fasting MGO was significantly higher in OM compared to YM (Median: 231 vs.158 nM, p=0.006), whereas no age differences in fasting 3-DG and GO concentrations were found. Glucose (310±71.8 versus 70.8±11.9 min·mmol/L) and insulin (7149±1249 versus 2827±493 min·µIU/mL) response were higher in OM compared to YM, which did not translate into a higher 1,2-dicarbonyl response in older individuals. Overall, aging does not necessarily result in dicarbonyl stress, indicating that strategies to cope with 1,2-dicarbonyl formation can remain intact.

Download Full-text

DOES THE ASSOCIATION BETWEEN AGE AND MAJOR ILLNESS VARY BY NATIONAL HEALTHCARE QUALITY?

Innovation in Aging ◽

10.1093/geroni/igz038.507 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S140-S140

Author(s):

Matthew A Andersson ◽

Lindsay R Wilkinson ◽

Markus H Schafer

Keyword(s):

Healthy Aging ◽

Subjective Evaluation ◽

Healthcare Quality ◽

Attributable Mortality ◽

Future Research ◽

Older Individuals ◽

Social Survey ◽

National Healthcare ◽

Age Related ◽

Major Illness

Abstract Though the risk of chronic disease and disability accelerates once adults are in their 60s, 70s, and 80s, researchers have long suspected that economic, social, and institutional variation — even among high-income Western nations — may powerfully influence the likelihood that people remain healthy at advanced ages. This study builds on comparative research into global aging, by offering a multiple-indicator test of whether national healthcare quality modifies the association between age and major illness. Recent individual-level data on morbidity among respondents aged 50 or older (16 countries; 2014 European Social Survey) are merged with nation-level healthcare indicators. Healthcare quality is assessed using a subjective, evaluation-based approach (based on the 2011 International Social Survey Programme) and an objective, attributable-mortality approach (2010 Healthcare Access and Quality, based on the Global Burden of Disease Study). Lagged nation-level economic and health indicators are controlled to help isolate healthcare effects. Multilevel logistic and linear regression models of any major health condition and morbidity reveal that while older individuals showed approximately a 10% reduction in probability of major illness when residing in countries with higher healthcare quality, associations between age and morbidity indices combining number and severity of illness showed greater modification by healthcare quality, with reductions around 18%. Results across subjective and objective approaches to healthcare quality are strikingly consistent. Taken together, results are suggestive of healthcare’s protective role in reducing age-related illness and disability. Future research should illuminate pathways by which healthcare quality may lead to differences in healthy aging among advanced nations.

Download Full-text

VACCINATION TO PROMOTE HEALTH THROUGHOUT LIFE AS A HEALTHY AGING STRATEGY

Innovation in Aging ◽

10.1093/geroni/igz038.771 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S211-S211

Author(s):

Leonard Friedland

Keyword(s):

Immune Response ◽

Healthy Aging ◽

New Technologies ◽

Older Age ◽

Target Antigen ◽

Older Individuals ◽

Demographic Shift ◽

Age Related ◽

Important Progress

Abstract This symposium addresses the role of vaccination to promote healthy aging, the process of developing and maintaining the functional ability that enables wellbeing in older age. Life-span immunization of adults across all age categories can help to reduce morbidity and mortality. Healthy aging is critical for our global society to counter the surge in healthcare costs that is coming as a result of the demographic shift to older age. Immune system function and response to vaccination declines with advancing age. Generating effective immune responses against new infectious disease targets can be difficult in older individuals. Important progress has been made in understanding the mechanisms underlying immunosenescence, the age-related decline of the immune response to infections and vaccinations. Innovative research and the development of new technologies, such as adjuvants, substances that can enhance and shape the immune response to the target antigen(s), has facilitated the development of vaccines specially tailored for adults. This evidence-based approach to the development of innovative vaccines addressing immunosenescence is an important clinically relevant healthy aging strategy to promote health throughout life.

Download Full-text

Gastrointestinal Microbiota and Their Contribution to Healthy Aging

Digestive Diseases ◽

10.1159/000443350 ◽

2016 ◽

Vol 34 (3) ◽

pp. 194-201 ◽

Cited By ~ 21

Author(s):

Anna Maria Mello ◽

Giulia Paroni ◽

Julia Daragjati ◽

Alberto Pilotto

Keyword(s):

Old Age ◽

Healthy Aging ◽

Adverse Outcomes ◽

Microbiota Composition ◽

Older Individuals ◽

Gastrointestinal Microbiota ◽

Targeted Interventions ◽

Age Related ◽

Increased Risk ◽

Older Subjects

Studies on populations at different ages have shown that after birth, the gastrointestinal (GI) microbiota composition keeps evolving, and this seems to occur especially in old age. Significant changes in GI microbiota composition in older subjects have been reported in relation to diet, drug use and the settings where the older subjects are living, that is, in community nursing homes or in a hospital. Moreover, changes in microbiota composition in the old age have been related to immunosenescence and inflammatory processes that are pathophysiological mechanisms involved in the pathways of frailty. Frailty is an age-related condition of increased vulnerability to stresses due to the impairment in multiple inter-related physiologic systems that are associated with an increased risk of adverse outcomes, such as falls, delirium, institutionalization, hospitalization and death. Preliminary data suggest that changes in microbiota composition may contribute to the variations in the biological, clinical, functional and psycho-social domains that occur in the frail older subjects. Multidimensional evaluation tools based on a Comprehensive Geriatric Assessment (CGA) have demonstrated to be useful in identifying and measuring the severity of frailty in older subjects. Thus, a CGA approach should be used more widely in clinical practice to evaluate the multidimensional effects potentially related to GI microbiota composition of the older subjects. Probiotics have been shown to be effective in restoring the microbiota changes of older subjects, promoting different aspects of health in elderly people as improving immune function and reducing inflammation. Whether modulation of GI microbiota composition, with multi-targeted interventions, could have an effect on the prevention of frailty remains to be further investigated in the perspective of improving the health status of frail ‘high risk' older individuals.

Download Full-text

Effect of Cognitive Control on Attentional Processing of Emotional Information Among Older Adults: Evidence From an Eye-Tracking Study

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.644379 ◽

2021 ◽

Vol 13 ◽

Author(s):

Haining Liu ◽

Haihong Liu ◽

Feng Li ◽

Buxin Han ◽

Cuili Wang

Keyword(s):

Older Adults ◽

Cognitive Control ◽

Eye Tracking ◽

Healthy Aging ◽

Older Individuals ◽

Younger Adults ◽

Spatial Cueing ◽

Age Related ◽

Cueing Task ◽

Engagement And Disengagement

Background: Although numerous studies have suggested that the gradually increasing selective preference for positive information over negative information in older adults depends on cognitive control processes, few have reported the characteristics of different attention stages in the emotional processing of older individuals. The present study used a real-time eye-tracking technique to disentangle the attentional engagement and disengagement processes involved in age-related positivity effect (PE).Methods: Eye movement data from a spatial-cueing task were obtained for 32 older and 32 younger healthy participants. The spatial-cueing task with varied cognitive loads appeared to be an effective way to explore the role of cognitive control during the attention engagement and disengagement stages of emotion processing.Results: Compared with younger adults, older participants showed more positive gaze preferences when cognitive resources were sufficient for face processing at the attention engagement stage. However, the age-related PE was not observed at the attention disengagement stage because older adults had more difficulty disengaging from fearful faces than did the younger adults due to the consumption of attention by the explicit target judgment.Conclusion: The present study highlights how cognitive control moderates positive gaze preferences at different attention processing stages. These findings may have far-reaching implications for understanding, preventing, and intervening in unsuccessful aging and, thus, in promoting active and healthy aging.

Download Full-text

Which Physiological Swallowing Parameters Change with Healthy Aging?

10.21926/obm.geriatr.2101153 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Renata Mancopes ◽

Pooja Gandhi ◽

Sana Smaoui ◽

Catriona M. Steele ◽

◽

...

Keyword(s):

Healthy Aging ◽

Upper Esophageal Sphincter ◽

Hierarchical Regression ◽

Bolus Transit ◽

Volume Number ◽

Healthy Older Adults ◽

Age Related ◽

Ues Opening ◽

Pharyngeal Area ◽

Age Related Changes

Research suggests there are age-related changes in swallowing that do not constitute impairment (“presbyphagia”). The goal of this study was to explore the influence of age on quantitative measures of healthy swallowing by controlling for the effects of sex and sip volume in order to determine the specific characteristics of presbyphagia. Videofluoroscopy recordings of thin liquid swallows from 76 healthy adults (38 male), aged 21-82 were analysed. Blinded duplicate ratings of swallowing safety, efficiency, kinematics, and timing were made using the ASPEKT method. Hierarchical regression models were used to determine the effects of age, sex, and sip-volume on swallowing. There were no age-related changes in sip volume, number of swallows per bolus, frequency or severity of penetration-aspiration, duration of the hyoid-burst (HYB)-to-upper-esophageal-sphincter (UES) opening interval, time-to-laryngeal-vestibule-closure (LVC), peak hyoid position, hyoid speed, or pharyngeal residue. Significant changes seen with increasing age included: longer swallow reaction time, UES opening duration and LVC duration; larger pharyngeal area at rest and maximum constriction; and wider UES diameter. Male participants had larger sip volume and pharyngeal area at rest. Larger sip volumes were associated with multiple swallows per bolus and shorter hyoid-burst-to-UES opening intervals. These results help to define presbyphagic changes in swallowing that can be expected in healthy older adults up to 80 years of age, and distinguish them from changes that represent impairment. Certain parameters showed changes that were opposite in direction to changes that are usually considered to reflect impairment: longer UES opening, longer LVC duration and wider UES opening. These changes may reflect possible compensations for slower bolus transit. Further research is needed to determine the points along the age continuum where observed age-related changes in swallowing begin to emerge.

Download Full-text

Inhibition and Switching in Healthy Aging: A Longitudinal Study

Journal of the International Neuropsychological Society ◽

10.1017/s1355617716000898 ◽

2016 ◽

Vol 23 (1) ◽

pp. 90-97 ◽

Cited By ~ 14

Author(s):

Steinunn Adólfsdóttir ◽

Daniel Wollschlaeger ◽

Eike Wehling ◽

Astri J. Lundervold

Keyword(s):

Processing Speed ◽

Predictive Value ◽

Healthy Aging ◽

Older Individuals ◽

Longitudinal Models ◽

Cross Sectional ◽

Gender And Education ◽

Age Related ◽

Speed Measure ◽

Interference Test

AbstractObjectives: Discrepant findings of age-related effects between cross-sectional and longitudinal studies on executive function (EF) have been described across different studies. The aim of the present study was to examine longitudinal age effects on inhibition and switching, two key subfunctions of EF, calculated from results on the Color Word Interference Test (CWIT). Methods: One hundred twenty-three healthy aging individuals (average age 61.4 years; 67% women) performed the CWIT up to three times, over a period of more than 6 years. Measures of inhibition, switching, and combined inhibition and switching were analyzed. A longitudinal linear mixed effects models analysis was run including basic CWIT conditions, and measures of processing speed, retest effect, gender, education, and age as predictors. Results: After taking all predictors into account, age added significantly to the predictive value of the longitudinal models of (i) inhibition, (ii) switching, and (iii) combined inhibition and switching. The basic CWIT conditions and the processing speed measure added to the predictive value of the models, while retest effect, gender, and education did not. Conclusions: The present study on middle-aged to older individuals showed age-related decline in inhibition and switching abilities. This decline was retained even when basic CWIT conditions, processing speed, attrition, gender, and education were controlled. (JINS, 2017, 23, 90–97)

Download Full-text

Impaired sensitivity to spatial configurations in healthy aging

10.31234/osf.io/h5x6g ◽

2021 ◽

Author(s):

James Chard ◽

Richard Cook ◽

Clare Press

Keyword(s):

Older Adults ◽

Face Processing ◽

Healthy Aging ◽

Drift Diffusion ◽

Younger Adults ◽

Healthy Older Adults ◽

Configural Information ◽

Age Related ◽

Spatial Configurations ◽

Social Difficulties

Studies have found age-related deficits in face processing, including identity and emotion recognition. It is unclear what underlies such atypicalities, and why older adults are unaffected in other apparently similar perceptual tasks. The present study examined the possibility that particular deficits in configural processing impair the perception of faces in healthy aging. Across two signal detection experiments, we required a group of healthy older adults and matched younger adults to detect changes in images of faces that could differ either at the local, featural level, or in configuration of these features. In support of our hypothesis, older adults were particularly impaired in detecting configural changes, relative to detecting changes in features. The impairments were found for both upright and inverted faces and were similar in a task with images of inanimate objects (houses). Drift diffusion modelling suggested that this decline related to reduced evidence accumulation rather than a tendency to make configural judgments based on less evidence. These findings indicate that domain-general problems processing configural information contribute to the difficulties with face processing in healthy aging, and may in principle also contribute to a range of higher-level social difficulties.

Download Full-text

Age Differences and Longitudinal Change in Exposure to Daily Stressors: Three Waves of Diary Data Across 20 Years

Innovation in Aging ◽

10.1093/geroni/igab046.824 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 215-215

Author(s):

Eric Cerino ◽

Jonathan Rush ◽

Robert Stawski

Keyword(s):

Age Differences ◽

Healthy Aging ◽

Later Life ◽

Longitudinal Change ◽

National Study ◽

Older Individuals ◽

Daily Stress ◽

Cross Sectional ◽

Telephone Interviews ◽

Age Related

Abstract Exposure to daily stress is an important risk factor for healthy aging. We examined cross-sectional age-related differences and longitudinal aging-related change in stressor exposure across three waves of the National Study of Daily Experiences (N=2,914, M=51.53 years, SD=13.55, 56.35% Female) spanning 20 years. Exposure to six types of stressors (arguments, avoided arguments, work overloads, home overloads, network stressors, other) were obtained from telephone interviews over 8 consecutive days in waves conducted in ~1996, ~2008, and ~2017. Longitudinal analyses revealed declines in stressor exposure across 20 years (p<.01), driven by declines in arguments, work overloads, and network stressors specifically. Cross-sectional analyses indicated that older individuals reported stressors less frequently (p<.01), driven by decreases in arguments, avoided arguments, work overloads, and home overloads specifically. Rates of longitudinal decline did not depend on age at baseline. Results suggest that aging-related changes and baseline age differences inform daily stress trajectories in mid- and later-life.

Download Full-text

Nutrients and Pathways that Regulate Health Span and Life Span

Geriatrics ◽

10.3390/geriatrics5040095 ◽

2020 ◽

Vol 5 (4) ◽

pp. 95

Author(s):

Carla Pignatti ◽

Stefania D’Adamo ◽

Claudio Stefanelli ◽

Flavio Flamigni ◽

Silvia Cetrullo

Keyword(s):

Health Status ◽

Life Span ◽

Healthy Aging ◽

Molecular Mechanisms ◽

Dietary Habits ◽

Human Life ◽

Nutrient Sensing ◽

Model Organisms ◽

Health Span ◽

Nutritional Conditions

Both life span and health span are influenced by genetic, environmental and lifestyle factors. With the genetic influence on human life span estimated to be about 20–25%, epigenetic changes play an important role in modulating individual health status and aging. Thus, a main part of life expectance and healthy aging is determined by dietary habits and nutritional factors. Excessive or restricted food consumption have direct effects on health status. Moreover, some dietary interventions including a reduced intake of dietary calories without malnutrition, or a restriction of specific dietary component may promote health benefits and decrease the incidence of aging-related comorbidities, thus representing intriguing potential approaches to improve healthy aging. However, the relationship between nutrition, health and aging is still not fully understood as well as the mechanisms by which nutrients and nutritional status may affect health span and longevity in model organisms. The broad effect of different nutritional conditions on health span and longevity occurs through multiple mechanisms that involve evolutionary conserved nutrient-sensing pathways in tissues and organs. These pathways interacting each other include the evolutionary conserved key regulators mammalian target of rapamycin, AMP-activated protein kinase, insulin/insulin-like growth factor 1 pathway and sirtuins. In this review we provide a summary of the main molecular mechanisms by which different nutritional conditions, i.e., specific nutrient abundance or restriction, may affect health span and life span.

Download Full-text