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"Healthy aging"
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From discoveries in ageing research to therapeutics for healthy ageing
For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. Here we summarize the milestones that mark this scientific triumph, discuss different ageing pathways and processes, and suggest that ageing research is entering a new era that has unique medical, commercial and societal implications. We argue that this era marks an inflection point, not only in ageing research but also for all biological research that affects the human healthspan.
The milestones that mark the advances in ageing research, the medical, commercial and societal implications of ageing and the different ageing pathways and processes that are associated with ageing are discussed.
Journal Article
Pilates for living : get stronger, fitter and healthier for an active later life
\"Pilates for living contains over 70 simple and effective exercises, suitable for all levels and abilities, with clear explanations, tips and modification suggestions. You will also find expert osteopathic advice and motivational interviews\"--Back cover.
Book
An aged immune system drives senescence and ageing of solid organs
Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly
1
,
2
. To define the contribution of immune system ageing to organism ageing, here we selectively deleted
Ercc1
, which encodes a crucial DNA repair protein
3
,
4
, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence
5
–
7
in the immune system only. We show that
Vav-iCre
+/−
;Ercc1
−/fl
mice were healthy into adulthood, then displayed premature onset of immunosenescence characterized by attrition and senescence of specific immune cell populations and impaired immune function, similar to changes that occur during ageing in wild-type mice
8
–
10
. Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing. The transplantation of splenocytes from
Vav-iCre
+/−
;Ercc1
−/fl
or aged wild-type mice into young mice induced senescence
in
trans
, whereas the transplantation of young immune cells attenuated senescence. The treatment of
Vav-iCre
+/−
;Ercc1
−/fl
mice with rapamycin reduced markers of senescence in immune cells and improved immune function
11
,
12
. These data demonstrate that an aged, senescent immune system has a causal role in driving systemic ageing and therefore represents a key therapeutic target to extend healthy ageing.
An aged, senescent immune system has a causal role in driving systemic ageing, and the targeting of senescent immune cells with senolytic drugs has the potential to suppress morbidities associated with old age.
Journal Article
Your best brain ever : a complete guide & workout
\"National Geographic presents a comprehensive guide to fighting mental decline. With cutting-edge neuroscience, information about Alzheimer's, fascinating case studies, and tips to fight brain aging symptoms such as slower mental acuity and \"senior moments,\" this smart, engaging guide will help keep your memory sharp and your mind active. Fun, age-defying exercises--from body stretches to word games to foods that help you think--help the brain perform at its best, just like exercising does for other parts of the body.\"-- Provided by publisher.
Book
Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states
Single-cell genomics technology has transformed our understanding of complex cellular systems. However, excessive cost and a lack of strategies for the purification of newly identified cell types impede their functional characterization and large-scale profiling. Here, we have generated high-content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all main hematopoietic cell types in healthy aging and leukemia. These reference maps enable the automatic design of cost-effective high-throughput cytometry schemes that outperform state-of-the-art approaches, accurately reflect complex topologies of cellular systems and permit the purification of precisely defined cell states. The systematic integration of cytometry and proteo-genomic data enables the functional capacities of precisely mapped cell states to be measured at the single-cell level. Our study serves as an accessible resource and paves the way for a data-driven era in cytometry.
Haas, Velten and colleagues use single-cell multiomics of human blood and bone marrow to generate a reference map allowing the quantitative linking of cytometry and proteo-genomic information.
Journal Article
Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing
Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed ‘optimally ageing’. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular — compensation, maintenance and reserve — have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.
Journal Article
Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice
Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and possibly to the longevity of the longest-lived rodent—the naked mole-rat
1
,
2
. To study whether the benefits of HMM-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmr
Has2
). nmr
Has2
mice showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmr
Has2
mice shifted towards that of longer-lived species. The most notable change observed in nmr
Has2
mice was attenuated inflammation across multiple tissues. HMM-HA reduced inflammation through several pathways, including a direct immunoregulatory effect on immune cells, protection from oxidative stress and improved gut barrier function during ageing. These beneficial effects were conferred by HMM-HA and were not specific to the nmr
Has2
gene. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exported to other species, and open new paths for using HMM-HA to improve lifespan and healthspan.
Mice overexpressing
Has2
from the naked mole-rat showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, attenuated inflammation through several pathways, extended lifespan and improved healthspan.
Journal Article
Integration of molecular profiles in a longitudinal wellness profiling cohort
An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, the authors sample a longitudinal wellness cohort and analyse blood molecular profiles as well as gut microbiota composition.
Journal Article