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1.
Hippocampal subfield volumes across the healthy lifespan and the effects of MR sequence on estimates.
Bussy, A, Plitman, E, Patel, R, Tullo, S, Salaciak, A, Bedford, SA, Farzin, S, Béland, ML, Valiquette, V, Kazazian, C, et al
NeuroImage. 2021;:117931
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Abstract
The hippocampus has been extensively studied in various neuropsychiatric disorders throughout the lifespan. However, inconsistent results have been reported with respect to which subfield volumes are most related to age. Here, we investigate whether these discrepancies may be explained by experimental design differences that exist between studies. Multiple datasets were used to collect 1690 magnetic resonance scans from healthy individuals aged 18-95 years old. Standard T1-weighted (T1w; MPRAGE sequence, 1 mm3 voxels), high-resolution T2-weighted (T2w; SPACE sequence, 0.64 mm3 voxels) and slab T2-weighted (Slab; 2D turbo spin echo, 0.4 × 0.4 × 2 mm3 voxels) images were included. The MAGeT Brain algorithm was used for segmentation of the hippocampal grey matter (GM) subfields and peri-hippocampal white matter (WM) subregions. Linear mixed-effect models and Akaike information criterion were used to examine linear, second or third order natural splines relationship between hippocampal volumes and age. We demonstrated that stratum radiatum/lacunosum/moleculare and fornix subregions expressed the highest relative volumetric decrease, while the cornus ammonis 1 presented a relative volumetric preservation of its volume with age. We also found that volumes extracted from slab images demonstrated different age-related relationships compared to volumes extracted from T1w and T2w images. The current work suggests that although T1w, T2w and slab derived subfield volumetric outputs are largely homologous, modality choice plays a meaningful role in the volumetric estimation of the hippocampal subfields.
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Cardiovascular Aging and Longevity: JACC State-of-the-Art Review.
Pietri, P, Stefanadis, C
Journal of the American College of Cardiology. 2021;(2):189-204
Abstract
Cardiovascular aging and longevity are interrelated through many pathophysiological mechanisms. Many factors that promote atherosclerotic cardiovascular disease are also implicated in the aging process and vice versa. Indeed, cardiometabolic disorders such as hyperglycemia, insulin resistance, dyslipidemia, and arterial hypertension share common pathophysiological mechanisms with aging and longevity. Moreover, genetic modulators of longevity have a significant impact on cardiovascular aging. The current knowledge of genetic, molecular, and biochemical pathways of aging may serve as a substrate to introduce interventions that might delay cardiovascular aging, thus approaching the goal of longevity. In the present review, the authors describe pathophysiological links between cardiovascular aging and longevity and translate these mechanisms into clinical data by reporting genetic, dietary, and environmental characteristics from long-living populations.
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Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs. Ketosis-Inducing Diet.
Napoleão, A, Fernandes, L, Miranda, C, Marum, AP
Nutrients. 2021;(4)
Abstract
As the incidence of Chronic Non-Communicable Diseases (CNCDs) increases, preventive approaches become more crucial. In this review, calorie restriction (CR) effects on human beings were evaluated, comparing the benefits and risks of different CR diets: classic CR vs. ketosis-inducing diets, including intermittent fasting (IF), classic ketogenic diet (CKD), fasting mimicking diet (FMD), very-low-calorie ketogenic Diet (VLCKD) and Spanish ketogenic Mediterranean diet (SKMD). Special emphasis on insulin resistance (IR) was placed, as it mediates metabolic syndrome (MS), a known risk factor for CNCD, and is predictive of MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.
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Temporal Leptin to Determine Cardiovascular and Metabolic Fate throughout the Life.
Kim, JG, Lee, BJ, Jeong, JK
Nutrients. 2020;(11)
Abstract
Leptin links peripheral adiposity and the central nervous system (CNS) to regulate cardiometabolic physiology. Within the CNS, leptin receptor-expressing cells are a counterpart to circulating leptin, and leptin receptor-mediated neural networks modulate the output of neuroendocrine and sympathetic nervous activity to balance cardiometabolic homeostasis. Therefore, disrupted CNS leptin signaling is directly implicated in the development of metabolic diseases, such as hypertension, obesity, and type 2 diabetes. Independently, maternal leptin also plays a central role in the development and growth of the infant during gestation. Accumulating evidence points to the dynamic maternal leptin environment as a predictor of cardiometabolic fate in their offspring as it is directly associated with infant metabolic parameters at birth. In postnatal life, the degree of serum leptin is representative of the level of body adiposity/weight, a driving factor for cardiometabolic alterations, and therefore, the levels of blood leptin through the CNS mechanism, in a large part, are a strong determinant for future cardiometabolic fate. The current review focuses on highlighting and discussing recent updates for temporal dissection of leptin-associated programing of future cardiometabolic fate throughout the entire life.
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Wandering along the epigenetic timeline.
Topart, C, Werner, E, Arimondo, PB
Clinical epigenetics. 2020;(1):97
Abstract
BACKGROUND Increasing life expectancy but also healthspan seems inaccessible as of yet but it may become a reality in the foreseeable future. To extend lifespan, it is essential to unveil molecular mechanisms involved in ageing. As for healthspan, a better understanding of the mechanisms involved in age-related pathologies is crucial. MAIN BODY We focus on the epigenetic side of ageing as ageing is traced by specific epigenetic patterns and can be measured by epigenetic clocks. We discuss to what extent exposure to environmental factor, such as alcohol use, unhealthy diet, tobacco and stress, promotes age-related conditions. We focused on inflammation, cancer and Alzheimer's disease. Finally, we discuss strategies to reverse time based on epigenetic reprogramming. CONCLUSIONS Reversibility of the epigenetic marks makes them promising targets for rejuvenation. For this purpose, a better understanding of the epigenetic mechanisms underlying ageing is essential. Epigenetic clocks were successfully designed to monitor these mechanisms and the influence of environmental factors. Further studies on age-related diseases should be conducted to determine their epigenetic signature, but also to pinpoint the defect in the epigenetic machinery and thereby identify potential therapeutic targets. As for rejuvenation, epigenetic reprogramming is still at an early stage.
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The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence.
DeJong, EN, Surette, MG, Bowdish, DME
Cell host & microbe. 2020;(2):180-189
Abstract
The gut microbiota changes with age, but it is not clear to what degree these changes are due to physiologic changes, age-associated inflammation or immunosenescence, diet, medications, or chronic health conditions. Observational studies in humans find that there are profound differences between the microbiomes of long-lived and frail individuals, but the degree to which these differences promote or prevent late-life health is unclear. Studies in model organisms demonstrate that age-related microbial dysbiosis causes intestinal permeability, systemic inflammation, and premature mortality, but identifying causal relationships have been challenging. Herein, we review how physiological and immune changes contribute to microbial dysbiosis and the degree to which microbial dysbiosis contributes to late-life health conditions. We discuss the features of the aging microbiota that make it more amenable to diet and pre- and probiotic interventions. Health interventions that promote a diverse microbiome could influence the health of older adults.
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The Lisbon patient: exceptional longevity with HIV suggests healthy aging as an ultimate goal for HIV care.
Pintassilgo, I, Cesari, M, Santos, HN, Milic, J, Franconi, I, Mussini, C, Marques, N, Guaraldi, G
BMC infectious diseases. 2020;(1):290
Abstract
In the context of global aging, HIV infection has become a new chronic disease and requires innovative models of care. Treating isolated comorbidities represents a useless and potentially harmful practice at advanced age. Therefore, a patient-centered approach, in which the interventions are focused on the biology and function of the individual, with understanding of the importance of securing social and home environment that provides psychosocial support, better suits unmet health needs. We present a paradigmatic case of healthy aging: the first reported HIV-infected patient who achieved 100th of life - the Lisbon patient. The construct of healthy aging, recently introduced by the World Health Organization, is the best example of this comprehensive model and could represent the fourth target of UNAIDS agenda of the end of AIDS.
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Molecular and environmental factors regulating seed longevity.
Zinsmeister, J, Leprince, O, Buitink, J
The Biochemical journal. 2020;(2):305-323
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Abstract
Seed longevity is a central pivot of the preservation of biodiversity, being of main importance to face the challenges linked to global climate change and population growth. This complex, quantitative seed quality trait is acquired on the mother plant during the second part of seed development. Understanding what factors contribute to lifespan is one of the oldest and most challenging questions in plant biology. One of these challenges is to recognize that longevity depends on the storage conditions that are experimentally used because they determine the type and rate of deleterious conditions that lead to cell death and loss of viability. In this review, we will briefly review the different storage methods that accelerate the deteriorative reactions during storage and argue that a minimum amount of information is necessary to interpret the longevity data. Next, we will give an update on recent discoveries on the hormonal factors regulating longevity, both from the ABA signaling pathway but also other hormonal pathways. In addition, we will review the effect of both maternal and abiotic factors that influence longevity. In the last section of this review, we discuss the problems in unraveling cause-effect relationship between the time of death during storage and deteriorative reactions leading to seed ageing. We focus on the three major types of cellular damage, namely membrane permeability, lipid peroxidation and RNA integrity for which germination data on seed stored in dedicated seed banks for long period times are now available.
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The Gut Microbiome, Aging, and Longevity: A Systematic Review.
Badal, VD, Vaccariello, ED, Murray, ER, Yu, KE, Knight, R, Jeste, DV, Nguyen, TT
Nutrients. 2020;(12)
Abstract
Aging is determined by complex interactions among genetic and environmental factors. Increasing evidence suggests that the gut microbiome lies at the core of many age-associated changes, including immune system dysregulation and susceptibility to diseases. The gut microbiota undergoes extensive changes across the lifespan, and age-related processes may influence the gut microbiota and its related metabolic alterations. The aim of this systematic review was to summarize the current literature on aging-associated alterations in diversity, composition, and functional features of the gut microbiota. We identified 27 empirical human studies of normal and successful aging suitable for inclusion. Alpha diversity of microbial taxa, functional pathways, and metabolites was higher in older adults, particularly among the oldest-old adults, compared to younger individuals. Beta diversity distances significantly differed across various developmental stages and were different even between oldest-old and younger-old adults. Differences in taxonomic composition and functional potential varied across studies, but Akkermansia was most consistently reported to be relatively more abundant with aging, whereas Faecalibacterium, Bacteroidaceae, and Lachnospiraceae were relatively reduced. Older adults have reduced pathways related to carbohydrate metabolism and amino acid synthesis; however, oldest-old adults exhibited functional differences that distinguished their microbiota from that of young-old adults, such as greater potential for short-chain fatty acid production and increased butyrate derivatives. Although a definitive interpretation is limited by the cross-sectional design of published reports, we integrated findings of microbial composition and downstream functional pathways and metabolites, offering possible explanations regarding age-related processes.
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Dairy foods and bone health throughout the lifespan: a critical appraisal of the evidence.
Iuliano, S, Hill, TR
The British journal of nutrition. 2019;(7):763-772
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Abstract
The consumption of high-Ca, high-protein dairy foods (i.e. milk, cheese, yogurt) is advocated for bone health across the lifespan to reduce the risk of low-trauma fractures. However, to date, the anti-fracture efficacy of dairy food consumption has not been demonstrated in randomised controlled trials but inferred from cross-sectional and prospective studies. The anti-fracture efficacy of dairy food consumption is plausible, but testing this requires a robust study design to ensure outcomes are suitably answering this important public health question. The evidence of skeletal benefits of dairy food consumption is equivocal, not because it may not be efficacious but because the study design and execution are often inadequate. The key issues are compliance with dietary intervention, dropouts, sample sizes and most importantly lack of deficiency before intervention. Without careful appraisal of the design and execution of available studies, precarious interpretations of outcomes may be made from these poorly designed or executed studies, without consideration of how study design may be improved. Dairy food interventions in children are further hampered by heterogeneity in growth: in particular sex and maturity-related differences in the magnitude, timing, location and surface-specific site of bone accrual. Outcomes of studies combining children of different sexes and maturity status may be masked or exaggerated by these differences in growth, so inaccurate conclusions are drawn from results. Until these critical issues in study design are considered in future dairy food interventions, the anti-fracture efficacy of dairy food consumption may remain unknown and continue to be based on conjecture.