Current Aging Science - Volume 16, Issue 1, 2023

Partly because of its antioxidant and anti-inflammatory properties, cocoa flavanols have been examined in reversing age-related cognitive deficits. Epidemiological studies indicate a relation between flavonoid intake and the prevention of dementia. In confirmation of this relation, several pharmacological studies show the faster speed of responding and better executive performance in flavanol-treated aged or young subjects. The lack of any effect appears in some studies, especially in young subjects, perhaps due to the use of groups with high educational levels and the possibility of a ceiling effect. In several studies, neuropsychological ameliorations were followed by increases in cerebral blood flow. These results are in line with those of animal experimentation since improvements have been found in motor and spatial performances of young and aging mice or rats as well as animal models of Alzheimer’s disease and Parkinson’s disease. Improvements are also reported in biologic markers of Alzheimer’s disease, in particular an increase in soluble Aβ and a decrease in tau hyperphosphorylation.

Aging remains the fundamental cause of the increased rate of morbidity and mortality in the elderly. Despite continuing research, an integrative and holistic understanding of the molecular mechanisms and effects of aging is still elusive. This presents a major challenge in biogerontology, and therefore novel strategies aimed at integrating the multifaceted nature of aging for the identification and development of successful therapeutic targets are highly desirable. At present, cellular senescence, immunosenescence, and gut microbiota dysbiosis are key known modulators of aging. However, a cellular senescence-centric integrative view that relates to the seemingly distinct processes of immunosenescence and gut microbiota dysbiosis can be envisaged, which implies a more inclusive and targetable understanding of aging. The present manuscript discusses the emerging evidence and significance of cellular senescence vis-à-vis immunosenescence and gut microbiota dysbiosis in the development of potential anti-aging therapies. Underlying interconnections and mechanisms amongst these individual modulators have been deliberated to present a more coherent and tangible understanding of biological aging. It is emphasized that aging be studied within the integrative purview of these processes that may ultimately help devise a new inclusive and consolidated theory of aging with well-defined therapeutic targets.

Psycho-biological resilience is considered one of the most important factors in the epigenetics of aging. Cell senescence exhibits a series of possible biochemical derangements concerning mitochondria, proteasome, genome and membranes. Research has shown that resilience can be acquired through hormesis, a set of conservative and adaptive processes based on biphasic doseresponse to specific mild stressors, such as fasting, intake of polyphenols, exercising, physical and chemical stress and mental engagement. These stimuli were shown to elicit beneficial cellular metabolic pathways, such as sirtuin activation, mechanistic target of rapamycin and insulin growth factor- 1 downregulation, nuclear related factor 2 upregulation and autophagy. The complex of these resilience-building processes plays a documented role in longevity. Mitochondria are regarded as one of the core actors of aging processes and represent the main target of hormetic approaches [mitohormesis]; furthermore, the influence of the mind on mitochondria, and thus on the balance of health and disease has been recently established, leading to the so-called mitochondria psychobiology. Hence, psychologic and physical stress that reflects on these organelles may be regarded as a relevant factor in cell senescence, and thus the proposed “mitoresilience“ denomination may be pertinent within the biomedical science of aging. Finally, the quantification of individual resilience is becoming increasingly important in aging science, and the investigation of the autonomic nervous system through heart rate variability (HRV) proved to be a valid method to quantify this parameter. In conclusion, an integrated approach targeting hormetic pathways to improve psychophysical resilience (namely mitoresilience), supported by the monitoring of HRV, may represent a valuable option in longevity medicine.

Background: Frailty is a state of age-related physiological vulnerability resulting from impaired homeostatic reserve and a reduced capacity of the individual to withstand stress and an independent predictor of deleterious health outcomes among the aged. Early identification of people who are at risk for frailty is vital in preventing and minimizing its socio-economic consequences in low-resource countries like India. However, risk factors for frailty among Indian institutionalized older adults have been seldom explored. Objective: The objective of this study is to develop a prediction model for the risk of frailty among institutionalized older adults. Methods: This study adopted a case-control design, wherein institutionalized adults were categorized into frail and non-frail, using Fried’s criteria. Individuals above 55 years of age who could follow instructions without severe motor and cognitive impairment and terminal illness were recruited from nine conveniently selected institutions. Socio-demographic, lifestyle, behavioral, and physical performance factors were evaluated by including hundred participants. Results: Among the fourteen independent variables, age, cognition, income, functional mobility, polypharmacy and presence of more than 3 comorbidities were significant in univariate analysis. But adjusted odds ratio showed a statistical significance for low educational status, low income, poor functional mobility, and presence of more than 3 co-morbidities only, hence they were used for developing the prediction model. Conclusion: Low education status, low income, poor functional mobility, and presence of more than 3 comorbidities were found to have a significant association with the risk of frailty. A model has been developed to predict the risk and early identification of frailty among institutionalized older adults.

Background: Caregivers of chronically ill geriatric patients face several problems throughout the disease progression of the patients under their care. This is a prospective crosssectional study conducted from September 2017 to September 2018, including 130 caregivers of geriatric patients from Attica, Greece. Objectives: This study investigates caregivers’ anxiety, perception of changes in their lives, and quality of life. Methods: The questionnaires administered were the revised Bakas Caregiving Outcomes Scale (rBCOS), the State-Trait Anxiety Inventory (STAI), and the Linear Analogue Scale Assessment (LASA). Results: Influencing factors associated with rBCOS, STAI and LASA were care timespan and energy levels. Only the State Anxiety Scale and the Patient-caregiver Relationship rBCOS questionnaire seemed to be affected by a cancer diagnosis. Conclusion: Our findings revealed that anxiety, low quality of life, and perception of changes in the lives of caregivers are the underlying factors. Significant factors were time spent caring for the patient, the status of their relationship, the diagnosis, especially in life-threatening and life-limiting diseases, and the caregivers’ energy levels. These results are important in order to comprehend the lives of caregivers and assess by what means could the healthcare system and society further assist them.

Background: Liver stemness refers to the high regenerative capacity of the organ. This intrinsic regeneration capacity allows the restoration of post-resection liver function in up to 50% of liver donors. Liver cirrhosis is one of the terminal liver diseases with a defect in the intrinsic regeneration capacity. Several attempts to restore intrinsic regeneration capacity by conducting in vivo studies on stem cells in various organs have shown the positive impact of fasting on stemness. An increased capacity for stem cell proliferation and regeneration was reported due to fasting. Prolonged fasting (PF) has been reported to maintain the long-term proliferative ability of hematopoietic stem cells. However, clinical trials on intermittent fasting (IF) have not conclusively given positive results for fasting individuals. Objectives: This research aims to investigate the effect of fasting on liver stemness by comparing the expression of octamer-binding transcription factor 4 (Oct-4), cytokeratin 19 (CK-19), and peroxisome proliferator-activated receptor γ co-activator α (PGC-1α) in liver cells of fasted rabbits with rabbits fed ad libitum. This study compares two types of fasting, which are intermittent (16 hours) and prolonged (40 hours) fasting, for liver stemness and intrinsic regenerative capacity. Methods: A total of 18 rabbits were conditioned into 3 different groups. The first group was subjected to an ad libitum diet, the second to intermittent fasting (16-hour fasting), and the third to prolonged fasting (40-hour fasting). Afterward, the RNA was extracted from the liver tissues of each rabbit and analyzed via real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Relative expression was calculated using the Livak method. Results: Compared to the ad libitum diet, a greater increase was reported in PGC-1α, upregulated Oct4, and steady CK-19 gene expressions in the livers of intermittent fasting rabbits. Prolonged fasting increased PGC1α, reduced liver stemness, and a statistically insignificant decrease in intrinsic liver regenerative capacity. Conclusion: Intermittent fasting indicates preferable molecular alterations in liver stemness and intrinsic regenerative capacity compared to prolonged fasting.

Background: One of the most studied theories about aging comes from the accumulation of free radical generation, leading to oxidative stress. Resveratrol (RSV) is a polyphenolic compound that has been shown to act as an antioxidant in medical practice. Objective: To verify the antioxidant action of resveratrol (and its correlation with aging) in leukocytes from donors of different ages, mainly through the analysis of the three main enzymes of the antioxidant complex and the analysis of the SIRT1 signaling pathway. Methods: Luminol-dependent chemiluminescence assay was used to evaluate ROS and SIRT1. Antioxidant enzymes were evaluated by commercial kits. *p<0.05. Results: In all age groups, there was a reduction in reactive oxygen species (ROS) in cells stimulated with RSV. There was a positive correlation between its antioxidant effect and donor age. In younger individuals (20-39 years old), there was an increase in catalase activity in cells exposed to RSV. In the older groups (40-59 years old and 60-80 years old), RSV was able to increase the activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Through the analysis of SIRT1 it was possible to observe a silencing of the pathway in leukocytes treated with RSV during aging. Conclusion: RSV showed antioxidant activity in all age groups, although more pronounced in younger individuals. One of the mechanisms of action of the RSV is due to the increase in the activity of antioxidant enzymes, which varies according to the individual's age, especially through the modulation of important antioxidant pathways.

Background: The risk of falling increases with neuromusculoskeletal and cognitive changes resulting from aging. Physical exercise shows beneficial effects on the risk of falling, but the results are unknown when associated with cognitive activity dual-task (DT). Objective: The objective of the study was to evaluate the impacts of the Otago Exercise Program (OEP) plus DT cognitive activity on the risk of falling in older adults. Methods: 36 older adults (83.5 ± 5.7 years) participated in a quasi-experimental study, distributed in two experimental groups and a control group: 1) OEP (OEPG; n=12), 2) OEP plus DT (OEPDTG; n = 12), and a control group (CG; n=12). Older adults were evaluated at pre- and post- 12 weeks of intervention. The thresholds for the risk of falling were considered as multiparameter scores of the 10 Meter Walking Test (10MWT), evocative 10MWT, Timed Up and Go (TUG), Sit to Stand Test (STS), and The Four-Stage Balance Test (Four-Stage), and the Montreal Cognitive Assessment (MoCA), to test the cognitive impairment. Results: At baseline, all groups were homogeneous. Post-intervention, the experimental groups presented significant functional differences, in comparison to the CG, for 10MWT (OEPDTG: p= 0.002; OEPG: p= 0.002); evocative 10MWT (OEPDTG: p=0.001; OEPG: p=0.001); TUG (OEPDTG: p=0.034); STS (OEPDTG: plt;0.001; OEPG: p<0.001) and cognitive for MoCA (OEPDTG: plt;0.019). Significant intra-group differences (pre-post) were observed in all intervention groups, but none in CG. The risk of falling (Four-Stage) in experimental groups (OEPDTG: 33.3%; OEPG: 41.7%) was considerably lower than CG (83.3%). Conclusion: Otago Exercise Program alone can reduce the risk of falling due to improved functionality, but adding the dual task also improves cognitive capacity in older adults. The clinical significance of these interventions goes beyond statistics.

Aim: This study aimed to determine the possible interrelationships between sarcopenia and Alzheimer’s disease (AD). Background: Sarcopenia and AD are two common geriatric syndromes; however, the relationship between AD and sarcopenia has not been evaluated in detail so far. Objective: The objective is to evaluate the relationship between AD and sarcopenia. Methods: This cross-sectional study was performed retrospectively on 128 patients with probable AD, with a mean age of 76.56±7.54 years. Comprehensive Geriatric Assessment, including the activities of daily living (ADLs), malnutrition, frailty, mini-mental state examination (MMSE), and orthostatic hypotension was performed. Sarcopenia was defined according to the revised EWGSOP-2 criteria. Results: The frequency of probable sarcopenia and definitive sarcopenia was 54.7% and 18.7%, respectively. AD patients with probable sarcopenia had lower MMSE and ADLs scores and were frailer. Clinical dementia rating (CDR) score, MMSE, and basic and instrumental ADLs were independently related to probable sarcopenia in the patients (p=0.003, p<0.001, p=0.001, and p=0.001, respectively). The prevalence of probable sarcopenia in those with CDR 2 was higher than in those with CDR 0.5 and 1 (p=0.002). Conclusion: Our findings suggest that probable sarcopenia seems to be related to worse MMSE and ADLs scores and frailty in patients with AD and seems to be related to the severity of AD. Considering adverse health outcomes and the burden of sarcopenia on the patients and their caregivers, optimal care and treatment of sarcopenia in patients with AD are of great importance.