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1.
Role of senescence in the chronic health consequences of COVID-19.
Wissler Gerdes, EO, Vanichkachorn, G, Verdoorn, BP, Hanson, GJ, Joshi, AY, Murad, MH, Rizza, SA, Hurt, RT, Tchkonia, T, Kirkland, JL
Translational research : the journal of laboratory and clinical medicine. 2022;:96-108
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Abstract
While the full impact of COVID-19 is not yet clear, early studies have indicated that upwards of 10% of patients experience COVID-19 symptoms longer than 3 weeks, known as Long-Hauler's Syndrome or PACS (postacute sequelae of SARS-CoV-2 infection). There is little known about risk factors or predictors of susceptibility for Long-Hauler's Syndrome, but older adults are at greater risk for severe outcomes and mortality from COVID-19. The pillars of aging (including cellular senescence, telomere dysfunction, impaired proteostasis, mitochondrial dysfunction, deregulated nutrient sensing, genomic instability, progenitor cell exhaustion, altered intercellular communication, and epigenetic alterations) that contribute to age-related dysfunction and chronic diseases (the "Geroscience Hypothesis") may interfere with defenses against viral infection and consequences of these infections. Heightening of the low-grade inflammation that is associated with aging may generate an exaggerated response to an acute COVID-19 infection. Innate immune system dysfunction that leads to decreased senescent cell removal and/or increased senescent cell formation could contribute to accumulation of senescent cells with both aging and viral infections. These processes may contribute to increased risk for long-term COVID-19 sequelae in older or chronically ill patients. Hence, senolytics and other geroscience interventions that may prolong healthspan and alleviate chronic diseases and multimorbidity linked to fundamental aging processes might be an option for delaying, preventing, or alleviating Long-Hauler's Syndrome.
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Interventions for Frailty Among Older Adults With Cardiovascular Disease: JACC State-of-the-Art Review.
Ijaz, N, Buta, B, Xue, QL, Mohess, DT, Bushan, A, Tran, H, Batchelor, W, deFilippi, CR, Walston, JD, Bandeen-Roche, K, et al
Journal of the American College of Cardiology. 2022;(5):482-503
Abstract
With the aging of the world's population, a large proportion of patients seen in cardiovascular practice are older adults, but many patients also exhibit signs of physical frailty. Cardiovascular disease and frailty are interdependent and have the same physiological underpinning that predisposes to the progression of both disease processes. Frailty can be defined as a phenomenon of increased vulnerability to stressors due to decreased physiological reserves in older patients and thus leads to poor clinical outcomes after cardiovascular insults. There are various pathophysiologic mechanisms for the development of frailty: cognitive decline, physical inactivity, poor nutrition, and lack of social supports; these risk factors provide opportunity for various types of interventions that aim to prevent, improve, or reverse the development of frailty syndrome in the context of cardiovascular disease. There is no compelling study demonstrating a successful intervention to improve a global measure of frailty. Emerging data from patients admitted with heart failure indicate that interventions associated with positive outcomes on frailty and physical function are multidimensional and include tailored cardiac rehabilitation. Contemporary cardiovascular practice should actively identify patients with physical frailty who could benefit from frailty interventions and aim to deliver these therapies in a patient-centered model to optimize quality of life, particularly after cardiovascular interventions.
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Alzheimer's disease research progress in Australia: The Alzheimer's Association International Conference Satellite Symposium in Sydney.
Sexton, CE, Anstey, KJ, Baldacci, F, Barnum, CJ, Barron, AM, Blennow, K, Brodaty, H, Burnham, S, Elahi, FM, Götz, J, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;(1):178-190
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Abstract
The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.
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The relationship between telomere length and putative markers of vascular ageing: A systematic review and meta-analysis.
Kosmopoulos, M, Chiriacò, M, Stamatelopoulos, K, Tsioufis, C, Masci, PG, Kontogiannis, C, Mengozzi, A, Pugliese, NR, Taddei, S, Virdis, A, et al
Mechanisms of ageing and development. 2022;:111604
Abstract
Accelerated biological aging contributes to the evolution of cardiovascular disease. However, its influence on subclinical organ damage remains unclear. Leukocyte telomere length (LTL) is emerging as a marker of biological cardiovascular aging. We performed a systematic review and meta-analysis to assess the association between LTL and measures of end-organ damage. PubMed, Medline, Embase, Cinahl Plus, ClinicalTrials.gov, and grey literature databases were searched for studies that assessed the association of LTL with arterial pulse wave velocity (aPWV), carotid intima-media thickness (cIMT), left ventricular mass (LVM or LVMI), renal outcomes, coronary artery calcium (CAC) and presence of carotid plaques. In a sample of 7256 patients, we found that cIMT (pooled correlation coefficient (r) = -0.249; 95 %CI -0.37, -0.128) and aPWV (pooled r = -0.194; 95 % CI -0.290, -0.100) inversely correlate with LTL. Compared to aPWV, cIMT had a stronger correlation with LTL. Patients without carotid plaques had longer telomeres than patients with carotid plaques. Quantitative analyses documented LTL association with renal outcomes and CAC, but not with LVM/LVMI. Among measures of end-organ damage, cIMT and aPWV provide the most accurate information on the contribution of biological aging to the process of vascular remodeling/damage.
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Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Physical Exercise, Microbiota and Myokines.
Bilski, J, Pierzchalski, P, Szczepanik, M, Bonior, J, Zoladz, JA
Cells. 2022;(1)
Abstract
Obesity and ageing place a tremendous strain on the global healthcare system. Age-related sarcopenia is characterized by decreased muscular strength, decreased muscle quantity, quality, and decreased functional performance. Sarcopenic obesity (SO) is a condition that combines sarcopenia and obesity and has a substantial influence on the older adults' health. Because of the complicated pathophysiology, there are disagreements and challenges in identifying and diagnosing SO. Recently, it has become clear that dysbiosis may play a role in the onset and progression of sarcopenia and SO. Skeletal muscle secretes myokines during contraction, which play an important role in controlling muscle growth, function, and metabolic balance. Myokine dysfunction can cause and aggravate obesity, sarcopenia, and SO. The only ways to prevent and slow the progression of sarcopenia, particularly sarcopenic obesity, are physical activity and correct nutritional support. While exercise cannot completely prevent sarcopenia and age-related loss in muscular function, it can certainly delay development and slow down the rate of sarcopenia. The purpose of this review was to discuss potential pathways to muscle deterioration in obese individuals. We also want to present the current understanding of the role of various factors, including microbiota and myokines, in the process of sarcopenia and SO.
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Effects of dual-task interference on swallowing in healthy aging adults.
Krishnamurthy, R, Philip, R, Balasubramanium, RK, Rangarathnam, B
PloS one. 2021;(6):e0253550
Abstract
A wide body of literature has demonstrated that the neural representation of healthy swallowing is mostly bilateral, with one hemisphere dominant over the other. While several studies have demonstrated the presence of laterality for swallowing related functions among young adults, the data on older adults are still growing. The purpose of this paper is to investigate potential changes in hemispheric dominance in healthy aging adults for swallowing related tasks using a behavioral dual-task paradigm. A modified dual-task paradigm was designed to investigate the potential reduction in hemispherical specialization for swallowing function. Eighty healthy right-handed participants in the study were divided into two groups [Group 1: young adults (18-40 years) and Group 2: older adults (65 and above)]. All the participants performed a timed water swallow test at baseline and with two interference conditions (silent word repetition, and facial recognition). The results of the study revealed the following 1) a statistically significant effect of age on swallow performance; 2) statistically significant effect of each of the interference tasks on two of the swallow measures (VPS and VPT) in younger adults; and 3) no significant effect of the interference tasks on the swallowing performance of older adults. These findings suggest that aging substantially affects swallowing in older individuals, and this potentially accompanies a reduction in the hemispheric specialization for swallowing related tasks.
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Vitamin B-6 intake is related to physical performance in European older adults: results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) study.
Grootswagers, P, Mensink, M, Berendsen, AAM, Deen, CPJ, Kema, IP, Bakker, SJL, Santoro, A, Franceschi, C, Meunier, N, Malpuech-Brugère, C, et al
The American journal of clinical nutrition. 2021;(4):781-789
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Abstract
BACKGROUND Maintenance of high physical performance during aging might be supported by an adequate dietary intake of niacin, vitamins B-6 and B-12, and folate because these B vitamins are involved in multiple processes related to muscle functioning. However, not much is known about the association between dietary intake of these B vitamins and physical performance. OBJECTIVES The objectives of this study were to investigate the association between dietary intake of niacin, vitamins B-6 and B-12, and folate and physical performance in older adults and to explore mediation by niacin status and homocysteine concentrations. METHODS We used baseline data from the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) trial, which included n = 1249 healthy older adults (aged 65-79 y) with complete data on dietary intake measured with 7-d food records and questionnaires on vitamin supplement use and physical performance measured with the short physical performance battery and handgrip dynamometry. Associations were assessed by adjusted linear mixed models. RESULTS Intake of vitamin B-6 was related to lower chair rise test time [β: -0.033 ± 0.016 s (log); P = 0.043]. Vitamin B-6 intake was also significantly associated with handgrip strength, but for this association, a significant interaction effect between vitamin B-6 intake and physical activity level was found. In participants with the lowest level of physical activity, higher intake of vitamin B-6 tended to be associated with greater handgrip strength (β: 1.5 ± 0.8 kg; P = 0.051), whereas in participants in the highest quartile of physical activity, higher intake was associated with lower handgrip strength (β: -1.4 ± 0.7 kg; P = 0.041). No evidence was found for an association between intake of niacin, vitamin B-12, or folate and physical performance or for mediation by niacin status or homocysteine concentrations. CONCLUSIONS Vitamin B-6 intake was associated with better chair rise test time in a population of European healthy older adults and also with greater handgrip strength in participants with low physical activity only. Homocysteine concentrations did not mediate these associations. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.
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Coenzyme Q10 supplementation - In ageing and disease.
Aaseth, J, Alexander, J, Alehagen, U
Mechanisms of ageing and development. 2021;:111521
Abstract
Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial electron transport chain. It is also an antioxidant in cellular membranes and lipoproteins. All cells produce CoQ10 by a specialized cytoplasmatic-mitochondrial pathway. CoQ10 deficiency can result from genetic failure or ageing. Some drugs including statins, widely used by inter alia elderly, may inhibit endogenous CoQ10 synthesis. There are also chronic diseases with lower levels of CoQ10 in tissues and organs. High doses of CoQ10 may increase both circulating and intracellular levels, but there are conflicting results regarding bioavailability. Here, we review the current knowledge of CoQ10 biosynthesis and primary and acquired CoQ10 deficiency, and results from clinical trials based on CoQ10 supplementation. There are indications that supplementation positively affects mitochondrial deficiency syndrome and some of the symptoms of ageing. Cardiovascular disease and inflammation appear to be alleviated by the antioxidant effect of CoQ10. There is a need for further studies and well-designed clinical trials, with CoQ10 in a formulation of proven bioavailability, involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ10 treatment in neurodegenerative disorders, as well as in metabolic syndrome and its complications.
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Microalgal Lipid Extracts Have Potential to Modulate the Inflammatory Response: A Critical Review.
Conde, TA, Zabetakis, I, Tsoupras, A, Medina, I, Costa, M, Silva, J, Neves, B, Domingues, P, Domingues, MR
International journal of molecular sciences. 2021;(18)
Abstract
Noncommunicable diseases (NCD) and age-associated diseases (AAD) are some of the gravest health concerns worldwide, accounting for up to 70% of total deaths globally. NCD and AAD, such as diabetes, obesity, cardiovascular disease, and cancer, are associated with low-grade chronic inflammation and poor dietary habits. Modulation of the inflammatory status through dietary components is a very appellative approach to fight these diseases and is supported by increasing evidence of natural and dietary components with strong anti-inflammatory activities. The consumption of bioactive lipids has a positive impact on preventing chronic inflammation and consequently NCD and AAD. Thus, new sources of bioactive lipids have been sought out. Microalgae are rich sources of bioactive lipids such as omega-6 and -3 polyunsaturated fatty acids (PUFA) and polar lipids with associated anti-inflammatory activity. PUFAs are enzymatically and non-enzymatically catalyzed to oxylipins and have a significant role in anti and pro-resolving inflammatory responses. Therefore, a large and rapidly growing body of research has been conducted in vivo and in vitro, investigating the potential anti-inflammatory activities of microalgae lipids. This review sought to summarize and critically analyze recent evidence of the anti-inflammatory potential of microalgae lipids and their possible use to prevent or mitigate chronic inflammation.
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Magnesium in Infectious Diseases in Older People.
Dominguez, LJ, Veronese, N, Guerrero-Romero, F, Barbagallo, M
Nutrients. 2021;(1)
Abstract
Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.