scholarly journals A biomimetic natural sciences approach to understanding the mechanisms of ageing in burden of lifestyle diseases

2021 ◽  
Vol 135 (10) ◽  
pp. 1251-1272
Author(s):  
Lu Dai ◽  
Leon Schurgers ◽  
Paul G. Shiels ◽  
Peter Stenvinkel
Keyword(s):  
Nutrient Sensing ◽  
Laboratory Animals ◽  
Comparative Approach ◽  
Public Healthcare ◽  
Ageing Population ◽  
Related Disease ◽  
Age Related ◽  
Oxidative Protein Damage ◽  
In The Wild ◽  
Cell Matrix Interactions

Abstract The worldwide landscape of an ageing population and age-related disease brings with it huge socio-economic and public healthcare concerns across nations. Correspondingly, monumental human and financial resources have been invested in biomedical research, with a mission to decode the mechanisms of ageing and how these contribute to age-related disease. Multiple hallmarks of ageing have been identified that are common across taxa, highlighting their fundamental importance. These include dysregulated mitochondrial metabolism and telomeres biology, epigenetic modifications, cell–matrix interactions, proteostasis, dysregulated nutrient sensing, stem cell exhaustion, inflammageing and immuno-senescence. While our understanding of the molecular basis of ageing is improving, it remains a complex and multifactorial process that remains to be fully understood. A key aspect of the shortfall in our understanding of the ageing process lies in translating data from standard animal models to humans. Consequently, we suggest that a ‘biomimetic’ and comparative approach, integrating knowledge from species in the wild, as opposed to inbred genetically homogenous laboratory animals, can provide powerful insights into human ageing processes. Here we discuss some particularities and comparative patterns among several species from the animal kingdom, endowed with longevity or short lifespans and unique metabolic profiles that could be potentially exploited to the understanding of ageing and age-related diseases. Based upon lessons from nature, we also highlight several avenues for renewed focus in the pathophysiology of ageing and age-related disease (i.e. diet-microbiome-health axis, oxidative protein damage, adaptive homoeostasis and planetary health). We propose that a biomimetic alliance with collaborative research from different disciplines can improve our understanding of ageing and age-related diseases with long-term sustainable utility.

scholarly journals Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice

2019 ◽  
Author(s):  
Azar Asadi Shahmirzadi ◽  
Daniel Edgar ◽  
Chen-Yu Liao ◽  
Yueh-Mei Hsu ◽  
Mark Lucanic ◽  
...  
Keyword(s):  
Population Aging ◽  
Functional Decline ◽  
Tca Cycle ◽  
Multiple Organ ◽  
Nutrient Sensing ◽  
Laboratory Animals ◽  
Inflammatory Factors ◽  
Demographic Shift ◽  
Age Related ◽  
Aging Studies

AbstractThe decline in early life mortality since the 1950s has resulted in dramatic demographic shift towards aged population. Aging manifests as a decline in health, multiple organ dysfunction and increased vulnerability to diseases, which degrades quality of life. A verity of genetic and pharmacological interventions, mostly from non-vertebrate models, have been identified that can enhance lifespan. Whether these interventions extend healthspan, the disease free and functional period of life, has only sometimes been tested and is often a matter of debate. Human aging indices have been developed to assess elements of functional decline with aging (e.g. sarcopenia, cognitive function). However, corresponding comprehensive indices in mice are seldom applied to aging studies. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically-relevant healthspan measurements. Metabolism and aging are tightly connected and specific perturbations of nutrient-sensing pathways can enhance longevity in laboratory animals. Here we show that alpha-ketoglutarate (delivered in the form of a Calcium salt, CaAKG), a key metabolite in tricarboxylic (TCA) cycle that is reported to extend lifespan in worms, can significantly extend lifespan and healthspan in mice. AKG is involved in various fundamental processes including collagen synthesis and epigenetic changes. Due to its broad roles in multiple biological processes, AKG has been a subject of interest for researchers in various fields. AKG also influences several age-related processes, including stem cell proliferation and osteoporosis. To determine its role in mammalian aging, we administered CaAKG in 18 months old mice and determined its effect on the onset of frailty and survival, discovering that the metabolite promotes longer, healthier life associated with a decrease in levels of inflammatory factors. Interestingly the reduction in frailty was more dramatic than the increase in lifespan, leading us to propose that CaAKG compresses morbidity.

scholarly journals Anti-Inflamm-Ageing and/or Anti-Age-Related Disease Emerging Treatments: A Historical Alchemy or Revolutionary Effective Procedures?

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Carmela Rita Balistreri
Keyword(s):  
Big Data Analysis ◽  
Clinical Applications ◽  
Ageing Population ◽  
Biological Assays ◽  
Related Disease ◽  
Age Related ◽  
Emerging Treatments ◽  
Blood Stem Cells ◽  
Potential Benefits ◽  
Effective Procedures

The “long-life elixir” has long represented for humans a dream, a vanity’s sin for remaining young and to long survive. Today, because of ageing population phenomenon, the research of antiageing interventions appears to be more important than ever, for preserving health in old age and retarding/or delaying the onset of age-related diseases. A hope is given by experimental data, which evidence the possibility of retarding ageing in animal models. In addition, it has been also demonstrated in animal life-extending studies not only the possibility of increasing longevity but also the ability to retard the onset of age-related diseases. Interestingly, this recent evidence is leading to promise of obtaining the same effects in humans and resulting in benefits for their health in old ages. In order to achieve this goal, different approaches have been used ranging from pharmacological targeting of ageing, basic biological assays, and big data analysis to the recent use of young blood, stem cells, cellular, genetic, and epigenetic reprogramming, or other techniques of regenerative medicine. However, only a little fraction of these approaches has the features for being tested in clinical applications. Here, new emerging molecules, drugs, and procedures will be described, by evidencing potential benefits and limitations.

scholarly journals Rescuing Immunosenescence via Non-Specific Vaccination

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 231-239
Author(s):  
Alexander I. Mosa
Keyword(s):  
Immune Responses ◽  
The Elderly ◽  
Short Review ◽  
Functional Markers ◽  
Healthy Life ◽  
Related Disease ◽  
Age Related ◽  
Population Vulnerability ◽  
Mechanistic Basis ◽  
Promising Avenue

Discrepancies in lifespan and healthy-life span are predisposing populations to an increasing burden of age-related disease. Accumulating evidence implicates aging of the immune system, termed immunosenescence, in the pathogenesis of multiple age-related diseases. Moreover, immune dysregulation in the elderly increases vulnerability to infection and dampens pathogen-specific immune responses following vaccination. The health challenges manifesting from these age related deficits have been dramatically exemplified by the current SARS-CoV-2 pandemic. Approaches to either attenuate or reverse functional markers of immunosenescence are therefore urgently needed. Recent evidence suggests systemic immunomodulation via non-specific vaccination with live-attenuated vaccines may be a promising avenue to at least reduce aged population vulnerability to viral infection. This short review describes current understanding of immunosenescence, the historical and mechanistic basis of vaccine-mediated immunomodulation, and the outstanding questions and challenges required for broad adoption.

scholarly journals Targeting impaired nutrient sensing with repurposed therapeutics to prevent or treat age-related cognitive decline and dementia: A systematic review

2021 ◽  
Vol 67 ◽  
pp. 101302
Author(s):  
Benjamin Kioussis ◽  
Camilla S.L. Tuttle ◽  
Daniel S. Heard ◽  
Brian K. Kennedy ◽  
Nicola T. Lautenschlager ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cognitive Decline ◽  
Nutrient Sensing ◽  
Age Related ◽  
Age Related Cognitive Decline

scholarly journals Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease

Gerontology ◽  
2016 ◽  
Vol 63 (2) ◽  
pp. 103-117 ◽  
Author(s):  
Cia-Hin Lau ◽  
Yousin Suh
Keyword(s):  
Animal Models ◽  
Genetic Manipulation ◽  
Logic Gate ◽  
Therapeutic Interventions ◽  
Human Aging ◽  
Aging Research ◽  
Epigenome Editing ◽  
Related Disease ◽  
Age Related

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations.

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