scholarly journals Presidential Symposium: Physiological vs. Molecular Clocks, Studies From Mice to Humans

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 32-32
Author(s):  
Blanka Rogina
Keyword(s):  
Functional Decline ◽  
Biological Significance ◽  
Molecular Clocks ◽  
Cellular Mechanisms ◽  
Nutritional Interventions ◽  
Age Related ◽  
Increased Risk ◽  
Extended Longevity ◽  
Species Specific

Abstract Aging is associated with a functional decline in metabolic, physiological, proliferative, and tissue homeostasis leading to deterioration at the organismal level, and an increased risk for disease and death. Genetic, pharmacological and nutritional interventions have been successfully used to preserve metabolic health, which leads to preserved healthspan and extended longevity. However, the rate at which animals in a population become impaired by age-related frailty and disease is highly variable and several aging clocks that measure different age-modulated processes in the organism are being use as potential markers of the rate of aging. These molecular clocks allow to a more accurate quantification of the biological age of animals. Nevertheless, there is still room for further discussion in terms of the strengths and weaknesses of these biomarkers, in order to probe their biological significance, cellular mechanisms, and epidemiological potential to further explore their long-term benefit of increasing healthspan. This symposium will discuss new approaches to delineate physiological versus molecular clocks based on studies in mice and humans. We will also discuss species-specific metabolic mechanisms based on longitudinal studies in mice, monkeys and humans.

scholarly journals Metabolism and Aging: New Approaches to Nutrition and Diet in Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 736-737
Author(s):  
Blanka Rogina
Keyword(s):  
Longitudinal Studies ◽  
Calorie Restriction ◽  
Functional Decline ◽  
Metabolic Health ◽  
Tissue Homeostasis ◽  
Nutritional Interventions ◽  
New Approaches ◽  
Nutrition And Diet ◽  
Extended Longevity ◽  
Species Specific

Abstract Aging is associated with a functional decline in metabolic, physiological, proliferative, and tissue homeostasis leading to deterioration at an organismal level and increases risk for disease and death. Genetic, pharmacological and nutritional interventions have been successfully used to preserve metabolic health, which leads to preserved healthspan and extended longevity. This symposium will discuss new approaches to nutrition and diet and mechanisms underlying interventions such as calorie restriction and genetic CR. We will also discuss species-specific metabolic mechanisms based on longitudinal studies in mice, monkeys and humans.

scholarly journals Multiple genetic pathways regulating lifespan extension are neuroprotective in a G2019S LRRK2 nematode model of Parkinson’s disease

2020 ◽  
Author(s):  
Megan M. Senchuk ◽  
Jeremy M. Van Raamsdonk ◽  
Darren J. Moore
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Onset ◽  
Lifespan Extension ◽  
Disease Manifestation ◽  
Genetic Pathways ◽  
Dopaminergic Neurodegeneration ◽  
Age Related ◽  
Increased Risk ◽  
Extended Longevity

AbstractBackgroundMutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of late-onset, familial Parkinson’s disease (PD), and LRRK2 variants are associated with increased risk for sporadic PD. While advanced age represents the strongest risk factor for disease development, it remains unclear how different age-related pathways interact to regulate LRRK2-driven late-onset PD.FindingsIn this study, we employ a C.elegans model expressing PD-linked G2019S LRRK2 to examine the interplay between age-related pathways and LRRK2-induced dopaminergic neurodegeneration. We find that multiple genetic pathways that regulate lifespan extension can provide robust neuroprotection against mutant LRRK2. However, the level of neuroprotection does not strictly correlate with the magnitude of lifespan extension, suggesting that lifespan can be experimentally dissociated from neuroprotection. Using tissue-specific RNAi, we demonstrate that lifespan-regulating pathways, including insulin/IGF-1 signaling, TOR, and mitochondrial respiration, can be directly manipulated in neurons to mediate neuroprotection. We extend this finding for AGE-1/PI3K, where pan-neuronal versus dopaminergic neuronal restoration of AGE-1 reveals both cell-autonomous and non-cell-autonomous neuroprotective mechanisms downstream of insulin signaling.ConclusionsOur data demonstrate the importance of distinct lifespan-regulating pathways in the pathogenesis of LRRK2-linked PD, and suggest that extended longevity is broadly neuroprotective via the actions of these pathways at least in part within neurons. This study further highlights the complex interplay that occurs between cells and tissues during organismal aging and disease manifestation.

scholarly journals Riding the Crest of the Teachable Moment: Promoting Long-Term Health After the Diagnosis of Cancer

2005 ◽  
Vol 23 (24) ◽  
pp. 5814-5830 ◽  
Author(s):  
Wendy Demark-Wahnefried ◽  
Noreen M. Aziz ◽  
Julia H. Rowland ◽  
Bernardine M. Pinto
Keyword(s):  
Cancer Survivors ◽  
Behavioral Interventions ◽  
Fruits And Vegetables ◽  
Functional Decline ◽  
Adult Survivors ◽  
Lifestyle Changes ◽  
Prostate Cancer Survivors ◽  
Increased Risk ◽  
The Impact

Purpose Cancer survivors are at increased risk for several comorbid conditions, and many seek lifestyle change to reduce dysfunction and improve long-term health. To better understand the impact of cancer on adult survivors' health and health behaviors, a review was conducted to determine (1) prevalent physical health conditions, (2) persistent lifestyle changes, and (3) outcomes of previous lifestyle interventions aimed at improving health within this population. Methods Relevant studies from 1966 and beyond were identified through MEDLINE and PubMed searches. Results Cancer survivors are at increased risk for progressive disease but also for second primaries, osteoporosis, obesity, cardiovascular disease, diabetes, and functional decline. To improve overall health, survivors frequently initiate diet, exercise, and other lifestyle changes after diagnosis. However, those who are male, older, and less educated are less likely to adopt these changes. There also is selective uptake of messages, as evidenced by findings that only 25% to 42% of survivors consume adequate amounts of fruits and vegetables, and approximately 70% of breast and prostate cancer survivors are overweight or obese. Several behavioral interventions show promise for improving survivors' health-related outcomes. Oncologists can play a pivotal role in health promotion, yet only 20% provide such guidance. Conclusion With 64% of cancer patients surviving > 5 years beyond diagnosis, oncologists are challenged to expand their focus from acute care to managing the long-term health consequences of cancer. Although more research is needed, opportunities exist for oncologists to promote lifestyle changes that may improve the length and quality of life of their patients.

scholarly journals ‘A longitudinal room of possibilities’ – perspectives on the benefits of long-term preventive home visits: A qualitative study of nurses’ experiences

2019 ◽  
Vol 40 (1) ◽  
pp. 6-14
Author(s):  
Mette Tøien ◽  
Ida Torunn Bjørk ◽  
Lisbeth Fagerström
Keyword(s):  
Older Persons ◽  
Functional Decline ◽  
Home Visits ◽  
Healthcare Services ◽  
Service Planning ◽  
Structural Factors ◽  
Structured Interviews ◽  
Preventive Home Visits ◽  
Age Related

Preventive home visits carried out by healthcare professionals are intended to promote the health and independence of home-dwelling older persons and to prevent functional decline. The aim of this study was to describe nurses’ experiences of the benefits from long-term follow up with annual preventive home visits to older people in a Norwegian context. We conducted semi-structured interviews with nine nurses who performed the service. Manifest and latent content analysis revealed benefits within three themes: sustained ability to live independently and thrive despite age-related changes, eased transition to other healthcare services, and improved healthcare service planning. Two headlines describe the longitudinal processes involved in the creation of benefits: ‘The processes of establishing, sustaining, and widening a longitudinal room of possibilities’, and ‘The individualized health-promoting processes – the ongoing gardening work. Professional, contextual and structural factors influenced the nurses’ ability to support older persons’ changing needs during the aging process and thus their health and independence.

scholarly journals The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice

2021 ◽  
Author(s):  
Qixia Xu ◽  
Qiang Fu ◽  
Zi Li ◽  
Hanxin Liu ◽  
Ying Wang ◽  
...  
Keyword(s):  
Functional Decline ◽  
Clinical Intervention ◽  
Grape Seed ◽  
Tumour Microenvironment ◽  
Active Components ◽  
Specific Effects ◽  
Age Related ◽  
Increased Risk ◽  
Physical Dysfunction

AbstractAgeing-associated functional decline of organs and increased risk for age-related chronic pathologies is driven in part by the accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP). Here we show that procyanidin C1 (PCC1), a polyphenolic component of grape seed extract (GSE), increases the healthspan and lifespan of mice through its action on senescent cells. By screening a library of natural products, we find that GSE, and PCC1 as one of its active components, have specific effects on senescent cells. At low concentrations, PCC1 appears to inhibit SASP formation, whereas it selectively kills senescent cells at higher concentrations, possibly by promoting production of reactive oxygen species and mitochondrial dysfunction. In rodent models, PCC1 depletes senescent cells in a treatment-damaged tumour microenvironment and enhances therapeutic efficacy when co-administered with chemotherapy. Intermittent administration of PCC1 to either irradiated, senescent cell-implanted or naturally aged old mice alleviates physical dysfunction and prolongs survival. We identify PCC1 as a natural senotherapeutic agent with in vivo activity and high potential for further development as a clinical intervention to delay, alleviate or prevent age-related pathologies.

Long-term recreational gymnastics provides a clear benefit in age-related functional decline and bone loss. A prospective 6-year study

2006 ◽  
Vol 17 (8) ◽  
pp. 1154-1164 ◽  
Author(s):  
K. Uusi-Rasi ◽  
H. Sievänen ◽  
A. Heinonen ◽  
I. Vuori ◽  
T. J. Beck ◽  
...  
Keyword(s):  
Bone Loss ◽  
Functional Decline ◽  
Age Related

scholarly journals Older Patients’ Competence, Preferences, and Attitudes Toward Digital Technology Use: Explorative Study

10.2196/27005 ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e27005
Author(s):  
Rikke Terp ◽  
Lars Kayser ◽  
Tove Lindhardt
Keyword(s):  
Digital Literacy ◽  
Technology Use ◽  
Older Patients ◽  
Health Technology ◽  
Nutritional Interventions ◽  
Ehealth Literacy ◽  
Explorative Study ◽  
Age Related ◽  
Increased Risk ◽  
The Right

Background Malnutrition is prevalent in older patients, which is associated with severe consequences such as a decline in functional status, increased risk of readmission, and increased mortality. A tablet-based eHealth solution (Food‘n’Go) was recently developed and introduced at our clinic to support older patients’ involvement in nutritional interventions during their hospitalization, thereby enhancing their awareness and motivation for choosing the right food to obtain sufficient calorie and protein intake. To reap the full benefits from the eHealth solution, the technology should be introduced and accompanied by support that targets the end users’ competence level and needs. Objective In this study, we aimed to explore older patients’ readiness (ie, competence, preferences, and attitudes) toward the use of information and communication technology (ICT), and to identify the factors that may act as barriers or facilitators for their engagement with health technology. Methods A descriptive and explorative study was performed using triangulation of data derived from semistructured interviews and questionnaires (based on the Readiness and Enablement Index for Health Technology [READHY] instrument). Older hospitalized patients (age ≥65 years; N=25) were included from two hospitals in Denmark. Results The majority (16/25, 64%) of the older patients (median age 81 years) were users of ICT. The qualitative findings revealed that their experiences of benefits related to the use of ICT facilitated usage. Barriers for use of ICT were health-related challenges, limited digital literacy, and low self-efficacy related to ICT use due to age-related prejudices by their relatives and themselves. The qualitative findings were also reflected in the low median scores on the eHealth Literacy Questionnaire (eHLQ) READHY scales within dimensions addressing the user’s knowledge and skills (eHLQ1:1.8; eHLQ3: 2.0), and the user experience (eHLQ6: 2.0; eHLQ7: 1.5). Conclusions Older patients are potential users of ICT, but experience a variety of barriers for using eHealth. When introducing older patients to eHealth, it is important to emphasize the possible benefits, and to offer support targeting their knowledge, skills, and motivation.

scholarly journals Skeletal Muscle Transcriptome Alterations Related to Physical Function Decline in Older Mice

2021 ◽  
Author(s):  
Ted G Graber ◽  
Rosario Maroto ◽  
Jill Thompson ◽  
Steve Widen ◽  
Zhaohui Man ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Physical Function ◽  
Wheel Running ◽  
Tibialis Anterior Muscle ◽  
Functional Decline ◽  
Cellular Mechanisms ◽  
Running Activity ◽  
Age Related ◽  
Wheel Running Activity

One inevitable consequence of aging is the gradual deterioration of physical function and exercise capacity, driven in part by the adverse effect of age on muscle tissue. Our primary purpose was to determine the relationship between patterns of gene expression in skeletal muscle and this loss of physical function. We hypothesized that some genes changing expression with age would correlate with functional decline, or conversely with preservation of function. Male C57BL/6 mice (6-months old, 6m, 24-months, 24m, and 28+-months, 28m; all n=8) were tested for physical ability using a comprehensive functional assessment battery (CFAB). CFAB is a composite scoring system comprised of five functional tests: rotarod (overall motor function), grip strength (fore-limb strength), inverted cling (4-limb strength/endurance), voluntary wheel running (activity rate/volitional exercise), and treadmill (endurance). We then extracted total RNA from the tibialis anterior muscle, analyzed with Next Generation Sequencing RNAseq to determine differential gene expression during aging, and compared these changes to physical function. Aging resulted in gene expression differences >│1.0│ log2 fold change (multiple comparison adjusted p<0.05) in 219 genes in the 24m and in 6587 genes in the 28m. Linear regression with CFAB determined 253 differentially expressed genes strongly associated (R>0.70) with functional status in the 28m, and 22 genes in the 24m. We conclude that specific age-related transcriptomic changes are associated with declines in physical function, providing mechanistic clues. Future work will establish the underlying cellular mechanisms and the physiological relevance of these genes to age-related loss of physical function.

scholarly journals Efficacy of Nutritional Interventions as Stand-Alone or Synergistic Treatments with Exercise for the Management of Sarcopenia

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1991 ◽  
Author(s):  
Sarah Damanti ◽  
Domenico Azzolino ◽  
Carlotta Roncaglione ◽  
Beatrice Arosio ◽  
Paolo Rossi ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Strength Function ◽  
Functional Decline ◽  
Public Health Problem ◽  
Adverse Outcomes ◽  
Major Public Health Problem ◽  
Related Condition ◽  
Nutritional Interventions ◽  
Exercise Interventions ◽  
Age Related

Sarcopenia is an age-related and accelerated process characterized by a progressive loss of muscle mass and strength/function. It is a multifactorial process associated with several adverse outcomes including falls, frailty, functional decline, hospitalization, and mortality. Hence, sarcopenia represents a major public health problem and has become the focus of intense research. Unfortunately, no pharmacological treatments are yet available to prevent or treat this age-related condition. At present, the only strategies for the management of sarcopenia are mainly based on nutritional and physical exercise interventions. The purpose of this review is, thus, to provide an overview on the role of proteins and other key nutrients, alone or in combination with physical exercise, on muscle parameters.

scholarly journals Participant-Reported Symptoms and Their Effect on Long-Term Adherence in the International Breast Cancer Intervention Study I (IBIS I)

2017 ◽  
Vol 35 (23) ◽  
pp. 2666-2673 ◽  
Author(s):  
Samuel George Smith ◽  
Ivana Sestak ◽  
Anthony Howell ◽  
John Forbes ◽  
Jack Cuzick
Keyword(s):  
Breast Cancer ◽  
Intervention Study ◽  
Controlled Trial ◽  
Hormone Replacement ◽  
Menopausal Status ◽  
Preventive Therapy ◽  
Age Related ◽  
Increased Risk ◽  
Cancer Intervention

Purpose To assess the role of participant-reported symptoms on long-term adherence to preventive therapy in the United Kingdom sample of the International Breast Cancer Intervention Study (IBIS-I). IBIS-I was a randomized controlled trial that investigated the effectiveness of tamoxifen in reducing the risk of breast cancer among women at increased risk of the disease. Participants and Methods Women were randomly assigned to tamoxifen versus placebo (20 mg/day; n = 4,279). After 456 exclusions, 3,823 women were included in this analysis. Adherence (< 4.5 years or ≥ 4.5 years) was calculated using data from six monthly clinical visits. Analyses were adjusted for age, Tyrer-Cuzick risk, smoking, use of hormone replacement therapy, menopausal status, baseline menopausal symptoms, and treatment. Results Overall, 69.7% of women were adherent for at least 4.5 years (tamoxifen: 65.2% v placebo: 74.0%; P < .001). Differences in adherence between treatment arms were observed from 12 months onward (all P < .01) and were largest at 54 months. Dropout rates were highest in the first 12 to 18 months and decreased thereafter. Women reporting nausea/vomiting were less likely to be adherent in both the tamoxifen (odds ratio [OR], 0.57; 95% CI, 0.37 to 0.86; P = .007) and placebo (OR, 0.58; 95% CI, 0.37 to 0.93; P = .023) arms. Headaches were associated with adherence only in the placebo arm (OR, 0.62; 95% CI, 0.42 to 0.91; P = .016), whereas gynecologic symptoms were significant only in the tamoxifen arm (OR, 0.77; 95% CI, 0.62 to 0.97; P = .024). Effect sizes for each symptom on adherence were not significantly different between the treatment groups ( P > .05). In both treatment arms, we observed significant trends for lower adherence with increasing severity for all symptoms ( P < .01) except headaches ( P = .054). Conclusion In the IBIS-I trial, experiencing predefined symptoms in the first 6 months reduced long-term adherence. Effects were similar between treatment arms, suggesting that women were attributing age-related symptoms to preventive therapy. Interventions were required to support symptom management.

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