Approaching Multimorbidity From a Translational Geroscience Perspective

Abstract Multimorbidity describes the accumulated burden of chronic disease. Multimorbidity erodes physiologic reserve, increasing the risk of frailty, disability and death. Most older adults have at least one chronic health condition by age 65. Once established, many age-related conditions progress and accumulate with age. Geroscience holds that there are key biologic pathways that explain the increase with age in multimorbidity, frailty and disability Translation of geroscience principles to human studies requires careful assessment of biomarkers of these pathways and multisystem outcomes. In this symposium, translational researchers in geriatric medicine and gerontology will present current work to elucidate biologic underpinnings of aging and potential intervention targets. We will address whether blood biomarkers of aging processes are prognostic using combinatorial techniques and explore the potential for proteomics to identify novel pathways for health aging. New insights into the role of inflammation will be discussed with an emphasis on its relationship to multimorbidity. Brain aging will be considered with respect to the interactions between external stressors and resilience evaluating the role of ketone bodies which have immunomodulatory effects particularly on innate immune cells. Finally, the role of multimorbidity as an intervention target and potential intermediate outcomes including biomarkers will be presented with discussion of next steps needed to realize the potential for translational geroscience clinical trials to improve health span.

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The Role of Science and Advocacy Regarding a Chronic Health Condition

The Social Psychology of Politics - Social Psychological Applications to Social Issues ◽

10.1007/978-1-4615-0569-3_8 ◽

2002 ◽

pp. 157-172

Author(s):

Leonard A. Jason ◽

Renee R. Taylor ◽

Judith A. Richman

Keyword(s):

Chronic Health Condition ◽

Health Condition ◽

Chronic Health

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Modeling late-life adaptation in affective well-being under a severe chronic health condition: The case of age-related macular degeneration.

Psychology and Aging ◽

10.1037/0882-7974.21.4.703 ◽

2006 ◽

Vol 21 (4) ◽

pp. 703-714 ◽

Cited By ~ 24

Author(s):

Oliver K. Schilling ◽

Hans-Werner Wahl

Keyword(s):

Macular Degeneration ◽

Late Life ◽

Well Being ◽

Chronic Health Condition ◽

Health Condition ◽

Age Related Macular Degeneration ◽

Chronic Health ◽

Age Related

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Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms221910251 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10251

Author(s):

Vladimir Sukhorukov ◽

Dmitry Voronkov ◽

Tatiana Baranich ◽

Natalia Mudzhiri ◽

Alina Magnaeva ◽

...

Keyword(s):

Glial Cells ◽

Brain Aging ◽

Cellular Level ◽

Aging Brain ◽

The Past ◽

Age Related ◽

Accumulation Of Damage ◽

Quantity Control ◽

The Brain

Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.

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CDKN2A Gene Expression as a Potential Aging Biomarker in Dogs

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.660435 ◽

2021 ◽

Vol 8 ◽

Author(s):

Sára Sándor ◽

Kitti Tátrai ◽

Kálmán Czeibert ◽

Balázs Egyed ◽

Enikő Kubinyi

Keyword(s):

Gene Expression ◽

Kinase Inhibitor ◽

Brain Aging ◽

Model Organisms ◽

Aging Research ◽

Temporal Muscle ◽

Cyclin Dependent Kinase Inhibitor ◽

Age Related ◽

The Brain

Describing evolutionary conserved physiological or molecular patterns, which can reliably mark the age of both model organisms and humans or predict the onset of age-related pathologies has become a priority in aging research. The age-related gene-expression changes of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene have been well-documented in humans and rodents. However, data is lacking from other relevant species, including dogs. Therefore, we quantified the CDKN2A mRNA abundance in dogs of different ages, in four tissue types: the frontal cortex of the brain, temporal muscle, skin, and blood. We found a significant, positive correlation between CDKN2A relative expression values and age in the brain, muscle, and blood; however, no correlation was detected in the skin. The strongest correlation was detected in the brain tissue (CDKN2A/GAPDH: r = 0.757, p < 0.001), similarly to human findings, while the muscle and blood showed weaker, but significant correlation. Our results suggest that CDKN2A might be a potential blood-borne biomarker of aging in dogs, although the validation and optimization will require further, more focused research. Our current results also clearly demonstrate that the role of CDKN2A in aging is conserved in dogs, regarding both tissue specificity and a pivotal role of CDKN2A in brain aging.

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NEURONAL-SPECIFIC PROTEASOME AUGMENTATION VIA EXTENDS LIFESPAN AND REDUCES AGE-RELATED NEURODEGENERATION

Innovation in Aging ◽

10.1093/geroni/igz038.364 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S96-S97

Author(s):

Andrew M Pickering

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Nervous System ◽

Drosophila Melanogaster ◽

Stress Resistance ◽

Brain Aging ◽

Animal Kingdom ◽

Age Related ◽

And Function

Abstract Cognitive function declines with age throughout the animal kingdom and increasing evidence shows that disruption of the proteasome system contributes to this decline. The proteasome has important roles in multiple aspects of the nervous system, including synapse function and plasticity, as well as preventing cell death and senescence. We report that augmentation of proteasome function, using overexpression of the proteasome β5 subunit, enhances proteasome assembly and function. Significantly, we go on to show neuronal-specific proteasome augmentation slows age-related declines in measures of learning, memory, and circadian rhythmicity. Surprisingly neuronal specific proteasome augmentation of proteasome function also produces a robust increase of lifespan in Drosophila melanogaster. Our findings appear specific to the nervous system; ubiquitous proteasome overexpression increases oxidative stress resistance but does not impact lifespan and is detrimental to some healthspan measures. These findings demonstrate a key role of the proteasome system in brain aging.

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The Role of microRNAs in Organismal and Skin Aging

International Journal of Molecular Sciences ◽

10.3390/ijms21155281 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5281

Author(s):

Marta Gerasymchuk ◽

Viktoriia Cherkasova ◽

Olga Kovalchuk ◽

Igor Kovalchuk

Keyword(s):

Replicative Senescence ◽

Skin Aging ◽

Dermal Fibroblasts ◽

Telomere Maintenance ◽

Sirtuin 1 ◽

Aging Effects ◽

Inhibition Of Proliferation ◽

Biomarkers Of Aging ◽

Age Related

The aging process starts directly after birth and lasts for the entire lifespan; it manifests itself with a decline in an organism’s ability to adapt and is linked to the development of age-related diseases that eventually lead to premature death. This review aims to explore how microRNAs (miRNAs) are involved in skin functioning and aging. Recent evidence has suggested that miRNAs regulate all aspects of cutaneous biogenesis, functionality, and aging. It has been noted that some miRNAs were down-regulated in long-lived individuals, such as let-7, miR-17, and miR-34 (known as longevity-related miRNAs). They are conserved in humans and presumably promote lifespan prolongation; conversely, they are up-regulated in age-related diseases, like cancers. The analysis of the age-associated cutaneous miRNAs revealed the increased expression of miR-130, miR-138, and miR-181a/b in keratinocytes during replicative senescence. These miRNAs affected cell proliferation pathways via targeting the p63 and Sirtuin 1 mRNAs. Notably, miR-181a was also implicated in skin immunosenescence, represented by the Langerhans cells. Dermal fibroblasts also expressed increased the levels of the biomarkers of aging that affect telomere maintenance and all phases of the cellular life cycle, such as let-7, miR-23a-3p, 34a-5p, miR-125a, miR-181a-5p, and miR-221/222-3p. Among them, the miR-34 family, stimulated by ultraviolet B irradiation, deteriorates collagen in the extracellular matrix due to the activation of the matrix metalloproteinases and thereby potentiates wrinkle formation. In addition to the pro-aging effects of miRNAs, the plausible antiaging activity of miR-146a that antagonized the UVA-induced inhibition of proliferation and suppressed aging-related genes (e.g., p21WAF-1, p16, and p53) through targeting Smad4 has also been noticed. Nevertheless, the role of miRNAs in skin aging is still not fully elucidated and needs to be further discovered and explained.

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Changes of the Brain Synapses During Aging. New Aspects

Zeitschrift für Naturforschung C ◽

10.1515/znc-2001-11-1201 ◽

2001 ◽

Vol 56 (11-12) ◽

pp. 921-929 ◽

Cited By ~ 3

Author(s):

Kleopatra Schulpis ◽

Artemis Doulgeraki ◽

Stylianos Tsakiris

Keyword(s):

Successful Aging ◽

Brain Aging ◽

Aging Brain ◽

Compensatory Mechanisms ◽

Age Related ◽

Adaptive Mechanisms ◽

Functional Implications ◽

Effects Of Aging ◽

The Brain

Abstract The process of brain aging is an interaction of age-related losses and compensatory mechanisms. This review is focused on the changes of the synaptic number and structure, their functional implications, regarding neurotransmission, as well as the electrical activity of neuronal circuits. Moreover, the importance of calcium homeostasis is strongly emphasized. It is also suggested that many neuronal properties are preserved, as a result of adaptive mechanisms, and that a series of interdependent factors regulate brain aging. The "new fron tier" in research is the challenge of understanding the effects of aging, both to prevent degen erative diseases and reduce their consequences. New aspects are considered a) the role of nitric oxide, b) free radicals and apoptosis, c) impaired cerebral microcirculation, d) m eta bolic features of aging brain, e) the possible neuroprotective role of insulin-like growth factor-1 (IGF-1) and ovarian steroids and e) stress and aging. These numerous multifactorial approaches are essential to understand the process of aging. The more we learn about it, the more we realize how to achieve "successful" aging. M inireview

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Identifying and Understanding Barriers and Facilitators to Medication Adherence Among Marshallese Adults in Arkansas

Journal of Pharmacy Technology ◽

10.1177/8755122518786262 ◽

2018 ◽

Vol 34 (5) ◽

pp. 204-215 ◽

Cited By ~ 3

Author(s):

Pearl A. McElfish ◽

Michelle L. Balli ◽

Jonell S. Hudson ◽

Christopher R. Long ◽

Teresa Hudson ◽

...

Keyword(s):

Medication Adherence ◽

A Priori ◽

The United States ◽

Chronic Health Condition ◽

Health Condition ◽

Barriers And Facilitators ◽

Semistructured Interview ◽

Improve Medication Adherence

Background: Significant health disparities are present in Marshallese adults residing in the United States, most notably a high incidence of type 2 diabetes and other chronic conditions. There is limited research on medication adherence in the Marshallese population. Objective: This study explored perceptions of and experiences with medication adherence among Marshallese adults residing in Arkansas, with the aim of identifying and better understanding barriers and facilitators to medication adherence. Methods: Eligible participants were Marshallese adults taking at least one medication for a chronic health condition. Each participant completed a brief survey and semistructured interview conducted in Marshallese by a bilingual Marshallese staff member. Interviews were recorded, transcribed, and translated from Marshallese to English. Qualitative data were coded for a priori and emergent themes. Results: A total of 40 participants were included in the study. The most common contributing factor for nonadherence was forgetting to take medication (82%). A majority of participants (70%) reported difficulty paying for medicine, 45% reported at least one form of cost-related nonadherence, and 40% engaged in more than one cost-related nonadherence practice. Family support and medication pill boxes were identified as facilitators for medication adherence. The majority of the participants (76.9%) stated that they understood the role of a pharmacist. Participants consistently desired more education on their medications from pharmacy providers. Conclusion: This is the first study to explore barriers and facilitators to medication adherence among Marshallese patients. The findings can be used to develop methods to improve medication adherence among Marshallese.

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