scholarly journals Sex differences in biological aging with a focus on human studies

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sara Hägg ◽  
Juulia Jylhävä
Keyword(s):  
Sex Differences ◽  
Sex Chromosome ◽  
Current Knowledge ◽  
Individual Variability ◽  
Human Studies ◽  
Biological Aging ◽  
Theories Of Aging ◽  
Age Related ◽  
Complex Biological Process ◽  
The Life Course

Aging is a complex biological process characterized by hallmark features accumulating over the life course, shaping the individual's aging trajectory and subsequent disease risks. There is substantial individual variability in the aging process between men and women. In general, women live longer than men, consistent with lower biological ages as assessed by molecular biomarkers, but there is a paradox. Women are frailer and have worse health at the end of life, while men still perform better in physical function examinations. Moreover, many age-related diseases show sex-specific patterns. In this review, we aim to summarize the current knowledge on sexual dimorphism in human studies, with support from animal research, on biological aging and illnesses. We also attempt to place it in the context of the theories of aging, as well as discuss the explanations for the sex differences, for example, the sex-chromosome linked mechanisms and hormonally driven differences.

scholarly journals Sarcopenic Obesity in Africa: A Call for Diagnostic Methods and Appropriate Interventions

2021 ◽  
Vol 8 ◽  
Author(s):  
Amy E. Mendham ◽  
Lillemor Lundin-Olsson ◽  
Julia H. Goedecke ◽  
Lisa K. Micklesfield ◽  
Dirk L. Christensen ◽  
...  
Keyword(s):  
Life Course ◽  
Low Income ◽  
Musculoskeletal Diseases ◽  
Current Knowledge ◽  
Developmental Trajectories ◽  
Diagnostic Methods ◽  
Sarcopenic Obesity ◽  
Age Related ◽  
The Life Course ◽  
Diagnostic Criterion

This perspective aims to highlight the lack of current knowledge on sarcopenic obesity in Africa and to call for diagnostic methods and appropriate interventions. Sarcopenic obesity has been defined as obesity that occurs in combination with low muscle mass and function, which is typically evident in older adults. However, there has been no clear consensus on population-specific diagnostic criterion, which includes both gold-standard measures that can be used in a more advanced health care system, and surrogate measures that can be used in low-income settings with limited resources and funding. Importantly, low and middle-income countries (LMICs) across Africa are in an ongoing state of economic and social transition, which has contributed to an increase in the aging population, alongside the added burden of poverty, obesity, and associated co-morbidities. It is anticipated that alongside the increased prevalence of obesity, these countries will further experience an increase in age-related musculoskeletal diseases such as sarcopenia. The developmental origins of health and disease (DOHaD) approach will allow clinicians and researchers to consider developmental trajectories, and the influence of the environment, for targeting high-risk individuals and communities for treatment and/or prevention-based interventions that are implemented throughout all stages of the life course. Once a valid and reliable diagnostic criterion is developed, we can firstly assess the prevalence and burden of sarcopenic obesity in LMICs in Africa, and secondly, develop appropriate and sustainable interventions that target improved dietary and physical activity behaviors throughout the life course.

scholarly journals Whole Blood Metabolomics in Aging Research

2020 ◽  
Vol 22 (1) ◽  
pp. 175
Author(s):  
Hiroshi Kondoh ◽  
Masahiro Kameda ◽  
Mitsuhiro Yanagida
Keyword(s):  
Whole Blood ◽  
Experimental Models ◽  
Individual Variability ◽  
Human Longevity ◽  
Biological Aging ◽  
Epigenetic Factors ◽  
Aging Research ◽  
Targeted Analysis ◽  
Complex Biological Process ◽  
Global Aging

Diversity is observed in the wave of global aging because it is a complex biological process exhibiting individual variability. To assess aging physiologically, markers for biological aging are required in addition to the calendar age. From a metabolic perspective, the aging hypothesis includes the mitochondrial hypothesis and the calorie restriction (CR) hypothesis. In experimental models, several compounds or metabolites exert similar lifespan-extending effects, like CR. However, little is known about whether these metabolic modulations are applicable to human longevity, as human aging is greatly affected by a variety of factors, including lifestyle, genetic or epigenetic factors, exposure to stress, diet, and social environment. A comprehensive analysis of the human blood metabolome captures complex changes with individual differences. Moreover, a non-targeted analysis of the whole blood metabolome discloses unexpected aspects of human biology. By using such approaches, markers for aging or aging-relevant conditions were identified. This information should prove valuable for future diagnosis or clinical interventions in diseases relevant to aging.

scholarly journals Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics

2013 ◽  
Vol 305 (4) ◽  
pp. H459-H476 ◽  
Author(s):  
Emanuele Marzetti ◽  
Anna Csiszar ◽  
Debapriya Dutta ◽  
Gauthami Balagopal ◽  
Riccardo Calvani ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cardiovascular System ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Late Life ◽  
Age Related ◽  
Functional Consequences ◽  
Cardiovascular Aging ◽  
The Life Course

Advanced age is associated with a disproportionate prevalence of cardiovascular disease (CVD). Intrinsic alterations in the heart and the vasculature occurring over the life course render the cardiovascular system more vulnerable to various stressors in late life, ultimately favoring the development of CVD. Several lines of evidence indicate mitochondrial dysfunction as a major contributor to cardiovascular senescence. Besides being less bioenergetically efficient, damaged mitochondria also produce increased amounts of reactive oxygen species, with detrimental structural and functional consequences for the cardiovascular system. The age-related accumulation of dysfunctional mitochondrial likely results from the combination of impaired clearance of damaged organelles by autophagy and inadequate replenishment of the cellular mitochondrial pool by mitochondriogenesis. In this review, we summarize the current knowledge about relevant mechanisms and consequences of age-related mitochondrial decay and alterations in mitochondrial quality control in the cardiovascular system. The involvement of mitochondrial dysfunction in the pathogenesis of cardiovascular conditions especially prevalent in late life and the emerging connections with neurodegeneration are also illustrated. Special emphasis is placed on recent discoveries on the role played by alterations in mitochondrial dynamics (fusion and fission), mitophagy, and their interconnections in the context of age-related CVD and endothelial dysfunction. Finally, we discuss pharmacological interventions targeting mitochondrial dysfunction to delay cardiovascular aging and manage CVD.

scholarly journals Systematic Review of Studies on Telomere Lengths in Patients with Multiple Sclerosis

2020 ◽  
Author(s):  
Jan Bühring ◽  
Michael Hecker ◽  
Brit Fitzner ◽  
Uwe Klaus Zettl
Keyword(s):  
Multiple Sclerosis ◽  
Meta Analysis ◽  
Individual Variability ◽  
Biological Aging ◽  
Specific Cell ◽  
List Type ◽  
Healthy Controls ◽  
Telomere Attrition ◽  
Related Disease ◽  
Age Related

AbstractBACKGROUNDTelomeres are protective cap structures at the end of chromosomes that are essential for maintening genomic stability. Accelerated telomere shortening is related to premature cellular senescence. Shortened telomere lengths (TL) have been implicated in the pathogenesis of various chronic immune-mediated and neurological diseases.OBJECTIVEWe aimed to systematically review the current literature on the association of TL as a measure of biological age and multiple sclerosis (MS).METHODSA comprehensive literature search was conducted to identify original studies that presented data on TL in samples from MS patients. Quantitative and qualitative information was extracted from the articles to summarize and compare the studies.RESULTSA total of 51 articles were screened, and 7 of them were included in this review. In 6 studies, average TL were analyzed in peripheral blood cells, whereas in one study, bone marrow-derived cells were used. Four of the studies reported significantly shorter leukocyte TL in at least one MS subtype in comparison to healthy controls (p=0.003 in meta-analysis). Shorter telomeres in MS patients were found to be associated, independently of age, with greater disability, lower brain volume, increased relapse rate and more rapid conversion from relapsing to progressive MS. However, it remains unclear how telomere attrition in MS may be linked to oxidative stress, inflammation and age-related disease processes.CONCLUSIONSDespite few studies in this field, there is substantial evidence on the association of TL and MS. Variability in TL appears to reflect heterogeneity in clinical presentation and course. Further investigations in large and well-characterized cohorts are warranted. More detailed studies on TL of individual chromosomes in specific cell types may help to gain new insights into the pathomechanisms of MS.HighlightsThe relationship between aging and the pathophysiology and course of MS is not fully understoodWe have identified seven studies that analyzed telomere lengths (TL) in patients with MSOur meta-analysis revealed significantly shorter leukocyte TL in MS patients compared to healthy controlsThere is evidence that individual variability in biological aging reflects clinical heterogeneity in MSThe potential use of TL as a biomarker of age-related disease mechanisms deserves further investigation

scholarly journals Sexually divergent DNA methylation programs with hippocampal aging

2017 ◽  
Author(s):  
Dustin R. Masser ◽  
Niran Hadad ◽  
Hunter Porter ◽  
Colleen A. Mangold ◽  
Archana Unnikrishnan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Sex Differences ◽  
Biological Aging ◽  
Age Related ◽  
Genome Wide ◽  
Aging Response ◽  
Genomic Location ◽  
Methylation Patterns ◽  
Genomic Methylation

SummaryDNA methylation is a central regulator of genome function and altered methylation patterns are indicative of biological aging and mortality. Age-related cellular, biochemical, and molecular changes in the hippocampus lead to cognitive impairments and greater vulnerability to neurodegenerative disease that varies between the sexes. The role of hippocampal epigenomic changes with aging in these processes is unknown as no genome-wide analyses of age-related methylation changes have considered the factor of sex in a controlled animal model. High-depth, genome-wide bisulfite sequencing of young (3 month) and old (24 month) male and female mouse hippocampus revealed that while total genomic methylation amounts did not change with aging, specific sites in CG and non-CG (CH) contexts demonstrated age-related increases or decreases in methylation that were predominantly sexually divergent. Differential methylation with age for both CG and CH sites was enriched in intergenic, and intronic regions and under-represented in promoters, CG islands and specific enhancer regions in both sexes suggesting that certain genomic elements are especially labile with aging, even if the exact genomic loci altered are predominantly sex-specific. Life-long sex differences in autosomal methylation at CG and CH sites were also observed. The lack of genome-wide hypomethylation, sexually divergent aging response, and autosomal sex differences at CG sites were confirmed in human data. These data reveal sex as a previously unappreciated central factor of hippocampal epigenomic changes with aging. In total, these data demonstrate an intricate regulation of DNA methylation with aging by sex, cytosine context, genomic location, and methylation level.

scholarly journals Pathogenesis of Aging and Age-related Comorbidities in People with HIV: Highlights from the HIV ACTION Workshop

2020 ◽  
Vol 5 (1) ◽  
pp. 143 ◽  
Author(s):  
Dana Gabuzda ◽  
Beth D. Jamieson ◽  
Ronald G. Collman ◽  
Michael M. Lederman ◽  
Tricia H. Burdo ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Science Research ◽  
Review Article ◽  
Biological Aging ◽  
Epigenetic Clock ◽  
Research Gaps ◽  
Markers Of Inflammation ◽  
Age Related ◽  
Research Working Group ◽  
Key Questions

People with HIV (PWH) experience accentuated biological aging, as defined by markers of inflammation, immune dysfunction, and the epigenetic clock. They also have an elevated risk of multiple age-associated comorbidities. To discuss current knowledge, research gaps, and priorities in aging and age-related comorbidities in treated HIV infection, the NIH program staff organized a workshop held in Bethesda, Maryland in September 2019. This review article describes highlights of discussions led by the Pathogenesis/Basic Science Research working group that focused on three high priority topics: immunopathogenesis; the microbiome/virome; and aging and senescence. We summarize knowledge in these fields and describe key questions for research on the pathogenesis of aging and age-related comorbidities in PWH. Understanding the drivers and mechanisms underlying accentuated biological aging is a high priority that will help identify potential therapeutic targets to improve healthspan in older PWH.

scholarly journals Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Ricardo Pereira-Moreira ◽  
Elza Muscelli
Keyword(s):  
Glucose Transport ◽  
Insulin Action ◽  
Current Knowledge ◽  
Sglt2 Inhibitor ◽  
Proximal Tubules ◽  
Human Studies ◽  
Glucose Disposal ◽  
Diabetic Patients ◽  
Insulin Effect ◽  
Renal Gluconeogenesis

Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose disposal are some of the insulin actions, but little is known about a possible insulin effect on tubular glucose reabsorption. This review is aimed at synthesizing the current knowledge about insulin action on glucose handling by proximal tubules. Method. A systematic article selection from Medline (PubMed) and Embase between 2008 and 2019. 180 selected articles were clustered into topics (renal insulin handling, proximal tubule glucose transport, renal gluconeogenesis, and renal insulin resistance). Summary of Results. Insulin upregulates its renal uptake and degradation, and there is probably a renal site-specific insulin action and resistance; studies in diabetic animal models suggest that insulin increases renal SGLT2 protein content; in vivo human studies on glucose transport are few, and results of glucose transporter protein and mRNA contents are conflicting in human kidney biopsies; maximum renal glucose reabsorptive capacity is higher in diabetic patients than in healthy subjects; glucose stimulates SGLT1, SGLT2, and GLUT2 in renal cell cultures while insulin raises SGLT2 protein availability and activity and seems to directly inhibit the SGLT1 activity despite it activating this transporter indirectly. Besides, insulin regulates SGLT2 inhibitor bioavailability, inhibits renal gluconeogenesis, and interferes with Na+K+ATPase activity impacting on glucose transport. Conclusion. Available data points to an important insulin participation in renal glucose handling, including tubular glucose transport, but human studies with reproducible and comparable method are still needed.

scholarly journals Strategies and cognitive reserve to preserve lexical production in aging

GeroScience ◽  
2021 ◽  
Author(s):  
Monica Baciu ◽  
Sonja Banjac ◽  
Elise Roger ◽  
Célise Haldin ◽  
Marcela Perrone-Bertolotti ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Aging ◽  
Individual Variability ◽  
Future Research ◽  
Aging Effects ◽  
Main Hypothesis ◽  
Compensatory Strategies ◽  
Age Related ◽  
Complementary Domain

AbstractIn the absence of any neuropsychiatric condition, older adults may show declining performance in several cognitive processes and among them, in retrieving and producing words, reflected in slower responses and even reduced accuracy compared to younger adults. To overcome this difficulty, healthy older adults implement compensatory strategies, which are the focus of this paper. We provide a review of mainstream findings on deficient mechanisms and possible neurocognitive strategies used by older adults to overcome the deleterious effects of age on lexical production. Moreover, we present findings on genetic and lifestyle factors that might either be protective or risk factors of cognitive impairment in advanced age. We propose that “aging-modulating factors” (AMF) can be modified, offering prevention opportunities against aging effects. Based on our review and this proposition, we introduce an integrative neurocognitive model of mechanisms and compensatory strategies for lexical production in older adults (entitled Lexical Access and Retrieval in Aging, LARA). The main hypothesis defended in LARA is that cognitive aging evolves heterogeneously and involves complementary domain-general and domain-specific mechanisms, with substantial inter-individual variability, reflected at behavioral, cognitive, and brain levels. Furthermore, we argue that the ability to compensate for the effect of cognitive aging depends on the amount of reserve specific to each individual which is, in turn, modulated by the AMF. Our conclusion is that a variety of mechanisms and compensatory strategies coexist in the same individual to oppose the effect of age. The role of reserve is pivotal for a successful coping with age-related changes and future research should continue to explore the modulating role of AMF.

scholarly journals Sex Differences in the Triad of Acquired Sensorineural Hearing Loss

2021 ◽  
Vol 22 (15) ◽  
pp. 8111
Author(s):  
Kuang-Hsu Lien ◽  
Chao-Hui Yang
Keyword(s):  
Hearing Loss ◽  
Sex Differences ◽  
Sexual Dimorphism ◽  
Sensorineural Hearing Loss ◽  
Hormone Replacement ◽  
Modern Society ◽  
Sensorineural Hearing ◽  
Drug Induced ◽  
Age Related ◽  
Age Related Hearing Loss

The triad of noise-generated, drug-induced, and age-related hearing loss is the major cause of acquired sensorineural hearing loss (ASNHL) in modern society. Although these three forms of hearing loss display similar underlying mechanisms, detailed studies have revealed the presence of sex differences in the auditory system both in human and animal models of ASNHL. However, the sexual dimorphism of hearing varies among noise-induced hearing loss (NIHL), ototoxicity, and age-related hearing loss (ARHL). Importantly, estrogen may play an essential role in modulating the pathophysiological mechanisms in the cochlea and several reports have shown that the effects of hormone replacement therapy on hearing loss are complex. This review will summarize the clinical features of sex differences in ASNHL, compare the animal investigations of cochlear sexual dimorphism in response to the three insults, and address how estrogen affects the auditory organ at molecular levels.

scholarly journals Sex- and age‐dependent alterations of splenic immune cell profile and NK cell phenotypes and function in C57BL/6J mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Kelly B. Menees ◽  
Rachael H. Earls ◽  
Jaegwon Chung ◽  
Janna Jernigan ◽  
Nikolay M. Filipov ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sex Differences ◽  
Nk Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Spleen Weight ◽  
Age Related ◽  
And Function ◽  
Cell Phenotypes

Abstract Background Physiological homeostasis decline, immunosenescence, and increased risk for multiple diseases, including neurodegeneration, are all hallmarks of ageing. Importantly, it is known that the ageing process is sex-biased. For example, there are sex differences in predisposition for multiple age-related diseases, including neurodegenerative and autoimmune diseases. However, sex differences in age-associated immune phenotypes are not clearly understood. Results Here, we examined the effects of age on immune cell phenotypes in both sexes of C57BL/6J mice with a particular focus on NK cells. We found female-specific spleen weight increases with age and concordant reduction in the number of splenocytes per gram of spleen weight compared to young females. To evaluate sex- and age-associated changes in splenic immune cell composition, we performed flow cytometry analysis. In male mice, we observed an age-associated reduction in the frequencies of monocytes and NK cells; female mice displayed a reduction in B cells, NK cells, and CD8 + T cells and increased frequency of monocytes and neutrophils with age. We then performed a whole blood stimulation assay and multiplex analyses of plasma cytokines and observed age- and sex-specific differences in immune cell reactivity and basal circulating cytokine concentrations. As we have previously illustrated a potential role of NK cells in Parkinson’s disease, an age-related neurodegenerative disease, we further analyzed age-associated changes in NK cell phenotypes and function. There were distinct differences between the sexes in age-associated changes in the expression of NK cell receptors, IFN-γ production, and impairment of α-synuclein endocytosis. Conclusions This study demonstrates sex- and age-specific alterations in splenic lymphocyte composition, circulating cytokine/chemokine profiles, and NK cell phenotype and effector functions. Our data provide evidence that age-related physiological perturbations differ between the sexes which may help elucidate sex differences in age-related diseases, including neurodegenerative diseases, particularly Parkinson’s disease, where immune dysfunction is implicated in their etiology.

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