Showing posts with label aging. Show all posts
Showing posts with label aging. Show all posts

Monday, February 12, 2024

The Art of Doing Nothing

Deep into the Juniper/Cedar pollen allergy season in Austin TX, I'm being frustrated that I have so little energy to do things. It's as if my batteries can not muster more than a 10% charge. I try to tell myself that it's OK to 'just be", to do nothing, and have not been very successful at this.  So, I enjoyed  stumbling upon a  recent Guardian article, "The art of doing nothing: have the Dutch found the answer to burnout culture?," whose URL I pass on to MindBlog readers.  It describes the concept of 'niken,' or the Dutch art of doing nothing. It has  has ameliorated my concern over how little I have been getting done, and references a 2019 NYTimes article, "The Case for Doing Nothing" that went viral when it was first published.  Letting go of always finding problems that need to be solved let's one face  a question posed by the meditation guru Loch Kelly: "What is there when there are no problems to be solved?" Variants of this question have been addressed in a thread of numerous MindBlog posts that I have now largely drawn to a close.

Friday, December 22, 2023

Three common assumptions about inflammation, aging, and health that are probably wrong

The abstract of a recent PNAS article by Thomas W. McDade (motivated readers can obtain the whole article from me):  

Significance

Inflammation is one of the most important, and potent, physiological systems in the human body. It is widely assumed that levels of inflammation increase with age and that chronic inflammation contributes to cardiovascular diseases. This understanding of inflammation is based on studies of people living in affluent, industrialized settings with low burdens of infectious disease. A broader view, based on research conducted across a wider range of ecological settings globally, indicates that chronic inflammation is not necessarily a “normal” part of aging and that the association between inflammation and age-related diseases is not inevitable. It also suggests that environments early in development have lasting effects on the regulation of inflammation in adulthood, with implications for diseases of aging.
Abstract
Chronic inflammation contributes to the onset and progression of cardiovascular disease and other degenerative diseases of aging. But does it have to? This article considers the associations among inflammation, aging, and health through the lens of human population biology and suggests that chronic inflammation is not a normal nor inevitable component of aging. It is commonly assumed that conclusions drawn from research in affluent, industrialized countries can be applied globally; that aging processes leading to morbidity and mortality begin in middle age; and that inflammation is pathological. These foundational assumptions have shifted focus away from inflammation as a beneficial response to infection or injury and toward an understanding of inflammation as chronic, dysregulated, and dangerous. Findings from community-based studies around the world—many conducted in areas with relatively high burdens of infectious disease—challenge these assumptions by documenting substantial variation in levels of inflammation and patterns of association with disease. They also indicate that nutritional, microbial, and psychosocial environments in infancy and childhood play important roles in shaping inflammatory phenotypes and their contributions to diseases of aging. A comparative, developmental, and ecological approach has the potential to generate novel insights into the regulation of inflammation and how it relates to human health over the life course.

Friday, July 07, 2023

A meta-analysis questions the cognitive benefits of physical activity.

I give up. If anything was supposed to have been proven I would have thought it would be that exercise has a beneficial effect on brain health and cognition. Now Ciria et al. offer the following in Nature Human Biology:
Extensive research links regular physical exercise to an overall enhancement of cognitive function across the lifespan. Here we assess the causal evidence supporting this relationship in the healthy population, using an umbrella review of meta-analyses limited to randomized controlled trials (RCTs). Despite most of the 24 reviewed meta-analyses reporting a positive overall effect, our assessment reveals evidence of low statistical power in the primary RCTs, selective inclusion of studies, publication bias and large variation in combinations of pre-processing and analytic decisions. In addition, our meta-analysis of all the primary RCTs included in the revised meta-analyses shows small exercise-related benefits (d = 0.22, 95% confidence interval 0.16 to 0.28) that became substantially smaller after accounting for key moderators (that is, active control and baseline differences; d = 0.13, 95% confidence interval 0.07 to 0.20), and negligible after correcting for publication bias (d = 0.05, 95% confidence interval −0.09 to 0.14). These findings suggest caution in claims and recommendations linking regular physical exercise to cognitive benefits in the healthy human population until more reliable causal evidence accumulates.
I can not offer an informed opinion on this abstract because my usual access to journals through the University of Wisconsin library does not work with Nature Human Behavior. However, I can point you to an excellent commentary by Claudia Lopez Lloreda that discusses the meta-analysis done by Ciria et al. and gives a summary of several recent studies on exercise and brain health.

Wednesday, July 05, 2023

Why music training slows cognitive aging

A team of Chinese collaborators has reported experiments in the Oxford academic journal Cerebral Cortex titled "Functional gradients in prefrontal regions and somatomotor networks reflect the effect of music training experience on cognitive aging" which are stated to show that music training enhances the functional separation between regions across prefrontal and somatomotor networks, delaying deterioration in working memory performance and prefrontal suppression of prominant but irrelevant information. I'm passing on the abstract and a clip from the paper's conclusion, and can send interested readers the whole article. I think it is an important article but I find it is rendered almost unintelligble by Chinese to English translation issues. I'm surprised the journal let this article appear without further editing.
Studies showed that the top-down control of the prefrontal cortex (PFC) on sensory/motor cortices changes during cognitive aging. Although music training has demonstrated efficacy on cognitive aging, its brain mechanism is still far from clear. Current music intervention studies have paid insufficient attention to the relationship between PFC and sensory regions. Functional gradient provides a new perspective that allows researchers to understand network spatial relationships, which helps study the mechanism of music training that affects cognitive aging. In this work, we estimated the functional gradients in four groups, young musicians, young control, older musicians, and older control. We found that cognitive aging leads to gradient compression. Compared with young subjects, older subjects presented lower and higher principal gradient scores in the right dorsal and medial prefrontal and the bilateral somatomotor regions, respectively. Meanwhile, by comparing older control and musicians, we found a mitigating effect of music training on gradient compression. Furthermore, we revealed that the connectivity transitions between prefrontal and somatomotor regions at short functional distances are a potential mechanism for music to intervene in cognitive aging. This work contributes to understanding the neuroplasticity of music training on cognitive aging.
From the conclusion paragraph:
In a nutshell, we demonstrate the top-down control of prefrontal regions to the somatomotor network, which is associated with inhibitory function and represents a potential marker of cognitive aging, and reveal that music training may work by affecting the connectivity between the two regions. Although this work has investigated the neuroplasticity of music on cognitive aging by recruiting subjects of different age spans, the present study did not include the study of longitudinal changes of the same group. Further studies should include longitudinal follow-up of the same groups over time to more accurately evaluate the effect of music intervention on the process of cognitive aging.

Monday, March 13, 2023

Blood-derived signals as potent drivers of both age-related brain dysfunction and brain rejuvenation.

 An open source review from Bieri et al. has some nice graphics and tables summarizing the varieties of pro-aging and rejuvenating interventions.  Here is their abstract.:

Aging induces molecular, cellular and functional changes in the adult brain that drive cognitive decline and increase vulnerability to dementia-related neurodegenerative diseases. Leveraging systemic and lifestyle interventions, such as heterochronic parabiosis, administration of ‘young blood’, exercise and caloric restriction, has challenged prevalent views of brain aging as a rigid process and has demonstrated that aging-associated cognitive and cellular impairments can be restored to more youthful levels. Technological advances in proteomic and transcriptomic analyses have further facilitated investigations into the functional impact of intertissue communication on brain aging and have led to the identification of a growing number of pro-aging and pro-youthful factors in blood. In this review, we discuss blood-to-brain communication from a systems physiology perspective with an emphasis on blood-derived signals as potent drivers of both age-related brain dysfunction and brain rejuvenation.

Friday, March 10, 2023

An arthritis drug mimicks the anti-aging benefits of youthful blood transfusions

Some edited clips from the New Atlas description of research by Passegué and collaborators on rejuvenating the stem cells located in the blood marrow that produce blood cells:
An aging blood system, because it’s a vector for a lot of proteins, cytokines, and cells, has a lot of bad consequences for the organism...A 70-year-old with a 40-year-old blood system could have a longer healthspan, if not a longer lifespan.”
The bone marrow "niche" in which stem cells exist deteriorates over time and becomes overwhelmed by inflammation, which impairs the blood stem cells. One particular inflammatory signal, called IL-1B, is critical to impairing the blood stem cells... since this signal is already implicated in other inflammatory conditions, such as rheumatoid arthritis, there are already drugs in wide use that target it... the researchers used an arthritis drug called anakinra to block IL-1B in elderly mice, and found that the blood stem cells returned to a younger, healthier state. This helped improve the state of the niche, the function of the blood stem cells and the regeneration of blood cells. The treatment worked even better when the drug was administered throughout the life of the mice, not just when they were already old.
Animal tests don't always translate to humans, but this work suggests that treating elderly patients with anti-inflammatory drugs blocking IL-1B function should help with maintaining healthier blood production

Friday, March 03, 2023

Empathy lost and regained in a mouse model of dementia

A PNAS Journal Club article by Carolyn Beans points to work by Yao and colleagues that shows that a loss of empathy that is especially problematic for those experiencing frontotemporal dementia (FTD...a rare condition that often develops earlier in life than other types of dementia) can be linked to slowed activity in a particular brain region of a mouse model of FTD. When Yao and colleagues experimentally increased brain activity, empathy returned. Here is the technical abstract of Yao and collaborators:

 Highlights

• Mice display dmPFC-dependent emotional contagion and other-directed consolation
• Emotional contagion and other-directed consolation are blunted in aged c9FTD mice
• Aged c9FTD mice exhibit reduced pyramidal neuron excitability in the dmPFC
• Enhancing dmPFC activity rescues empathy loss in aged c9FTD mice
Summary
Empathic function is essential for the well-being of social species. Empathy loss is associated with various brain disorders and represents arguably the most distressing feature of frontotemporal dementia (FTD), a leading form of presenile dementia. The neural mechanisms are unknown. We established an FTD mouse model deficient in empathy and observed that aged somatic transgenic mice expressing GGGGCC repeat expansions in C9orf72, a common genetic cause of FTD, exhibited blunted affect sharing and failed to console distressed conspecifics by affiliative contact. Distress-induced consoling behavior activated the dorsomedial prefrontal cortex (dmPFC), which developed profound pyramidal neuron hypoexcitability in aged mutant mice. Optogenetic dmPFC inhibition attenuated affect sharing and other-directed consolation in wild-type mice, whereas chemogenetically enhancing dmPFC excitability rescued empathy deficits in mutant mice, even at advanced ages when substantial cortical atrophy had occurred. These results establish cortical hypoexcitability as a pathophysiological basis of empathy loss in FTD and suggest a therapeutic strategy.

Monday, January 16, 2023

COVID-19 and brain aging

Over the Christmas and New Year's holidays I was hit first by a mild Covid infection that lasted only a few days (I've had all 5 vaccinations and immediately took Paxlovid on testing positive) and then five days later had a slightly longer Paxlovid-rebound infection. A transient brain fog seems to have cleared by now. This personal experience makes me especially attentive to articles like Welberg's note on Covid-19 and brain aging, which suggests that brain changes associated with Covid infection are most likely due to neuroinflammation resulting from the infection, not from the virus itself. Here is the abstract:
Severe COVID-19 has been associated with cognitive impairment and changes in the frontal cortex. In a study published in Nature Aging, Mavrikaki, Lee et al. performed RNA sequencing on frontal cortex samples from 21 individuals with severe COVID-19, 22 age- and sex-matched uninfected controls, and 9 uninfected people who had received intensive care or ventilator treatment. The authors found almost 7,000 differentially expressed genes (DEGs) in the patient samples compared to controls. Upregulated DEGs were enriched for genes involved in immune-related pathways, and downregulated DEGs were enriched for genes involved in synaptic activity, cognition and memory — a profile of transcriptional changes that resembles those previously observed in aging brains. Direct comparisons between frontal cortex samples from young and old individuals confirmed this overlap. Application of tumor necrosis factor, interferon-β or interferon-γ to cultured human primary neurons induced transcriptional changes similar to those seen in patients with severe COVID-19. As no SARS-CoV-2 RNA was detected in the patient samples, these data suggest that the transcriptomic changes in frontal cortex of patients with severe COVID-19 were due to neuroinflammatory processes rather than a direct effect of the virus.

Monday, December 26, 2022

Rigorous study does not find that exercise and mindfulness training improve cognitive function in older adults.

Wow, here is a study by Lenze et al. - not confirming the results of numerous other less rigorous studies reported in MindBlog posts - that is unable to demonstrate that the use of mindfulness training, exercise, or a combination of both can significantly improving cognitive function in older adults with subjective cognitive concerns. In their randomized clinical trial that included 585 participants, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function composite scores at 6 months. Gretchen Reynolds provides context and a summary of the work in a Washington Post article.

Friday, December 23, 2022

A smart phone intervention that enhances memory in older adults.

Martin et al.  offer an open source article that describes a smartphone intervention that enhances real-world memory and promotes differentiation of hippocampal activity in older adults.  I have downloaded the HippoCamera smartphone App described in the text from the Apple App Store, and found a research passcode is required, for which the following clip of text from the article is relevant: "As of the time of writing, this is a research-dedicated application that requires an access code that can be obtained from a corresponding author."

Significance

The ability to vividly recollect our past declines with age, a trend that negatively impacts overall well-being. We show that using smartphone technologies to record and replay brief but rich memory cues from daily life can improve older adults’ ability to reexperience the past. This enhancement was associated with corresponding changes in the way memories were stored in the brain. Functional neuroimaging showed that repeatedly replaying memory cues drove memories apart from one another in the hippocampus, a brain region with well-established links to memory function. This increase in differentiation likely facilitated behavior by strengthening memory and minimizing competition among different memories at retrieval. This work reveals an easy-to-use intervention that helps older adults better remember their personal past.
Abstract
The act of remembering an everyday experience influences how we interpret the world, how we think about the future, and how we perceive ourselves. It also enhances long-term retention of the recalled content, increasing the likelihood that it will be recalled again. Unfortunately, the ability to recollect event-specific details and reexperience the past tends to decline with age. This decline in recollection may reflect a corresponding decrease in the distinctiveness of hippocampal memory representations. Despite these well-established changes, there are few effective cognitive behavioral interventions that target real-world episodic memory. We addressed this gap by developing a smartphone-based application called HippoCamera that allows participants to record labeled videos of everyday events and subsequently replay, high-fidelity autobiographical memory cues. In two experiments, we found that older adults were able to easily integrate this noninvasive intervention into their daily lives. Using HippoCamera to repeatedly reactivate memories for real-world events improved episodic recollection and it evoked more positive autobiographical sentiment at the time of retrieval. In both experiments, these benefits were observed shortly after the intervention and again after a 3-mo delay. Moreover, more detailed recollection was associated with more differentiated memory signals in the hippocampus. Thus, using this smartphone application to systematically reactivate memories for recent real-world experiences can help to maintain a bridge between the present and past in older adults.

Friday, November 04, 2022

Senescent cells targeted by anti-aging therapies may not be all bad

Michael Irving does a brief article in New Atlas that points to work by Reyes et al. showing that some senescent od the sort that accumulate with aging not only secrete inflammatory compounds that can be damaging to tisse around them, but also can play a positive role in repairing tissue damage. This suggests that senolytics research should focus on developing drugs that will target specific subsets of senescent cells that are implicated in disease rather than in regeneration.

Wednesday, September 21, 2022

Lasting improvements in seniors’ working and long-term memory with repetitive neuromodulation

From Grover et al., an open source article in which details of their transcranial alternating current stimulation (tACS) protocols are given:
The development of technologies to protect or enhance memory in older people is an enduring goal of translational medicine. Here we describe repetitive (4-day) transcranial alternating current stimulation (tACS) protocols for the selective, sustainable enhancement of auditory–verbal working memory and long-term memory in 65–88-year-old people. Modulation of synchronous low-frequency, but not high-frequency, activity in parietal cortex preferentially improved working memory on day 3 and day 4 and 1 month after intervention, whereas modulation of synchronous high-frequency, but not low-frequency, activity in prefrontal cortex preferentially improved long-term memory on days 2–4 and 1 month after intervention. The rate of memory improvements over 4 days predicted the size of memory benefits 1 month later. Individuals with lower baseline cognitive function experienced larger, more enduring memory improvements. Our findings demonstrate that the plasticity of the aging brain can be selectively and sustainably exploited using repetitive and highly focalized neuromodulation grounded in spatiospectral parameters of memory-specific cortical circuitry.

Friday, September 16, 2022

A 2020 MindBlog anti-aging experiment whose results I forgot to report to MindBlog readers.

How embarassing. While doing a scan of posts on aging to update my Jan. 2018 talk "How Much Can We Change Our Aging?" talk, I pulled up a post from Wed. Oct. 14, 2020 describing an experiment to test the effects of trying alpha-ketoglutarate (meant to promote mitochondrial metabolism) as a dietary supplement. I did not follow up on my promise to report and side effects in an addendum to the post. I have now done that, and below paste in the amended text:

I've done a bit more reading on alpha-ketoglutarate, a natural component of the Krebs biochemical cycle that generates body energy and whose levels normally decline with aging. It was the subject of a recent post pointing to studies indicating the positive effects of its supplementation on health and longevity in mice.  So...I have started taking 300 mg capsules of the stuff with my other breakfast supplements. I decided to pass on the pricey 'Rejuvant Life Tabs', containing 1000 mg and offered by Ponce de Leon Health, a company set up by some of the researchers, and instead got the compound from Kirkman, one of the supplement providers. I'm inclined not to be too paranoid about their sending sawdust instead of the real product.  I noted that I could buy the >98% pure dry powder from the Sigma-Aldrich company, the supplier my biochemisty lab used for over 30 years, but decided the hassle of dealing with bulk powder wasn't worth it.  The compound is quite acidic, so best taken as the Calcium or Magnesium salt and with a meal.  I had an unhappy tummy when I tried it without food.  

I will continue taking the compound, will report imagined positive or negative effects as addenda to this post.  Undesirable side effects will lead me to discontinue the supplement, as was the case with my 2010 (Acetyl L-carnitine, alpha-lipoic acid, and the B-vitamin biotin) and 2016 (pterostilbene and nicotinamide riboside) self experiments.  The latter, like a 2008 experiment with resveratrol was terminated because of increasing arthritic symptoms. The 2008 post had 33 comments reporting negative effects resveratrol.

And, a necessary comment regarding Ponce de Leon Health and other purveyors of life extension elixirs:

You're gonna die..there is compelling evidence that none of us will make it past ~120 years of age.   

ADDENDUM... added 9/1/2022 Apologies for spacing out for almost two years.... I took 300 mg capsules of alpha-ketoglutarate with breakfast for one week in early Nov. 2020. It caused acid reflux and increasing hand arthritis over the week. Both side effects vanished after a week off the supplement. I had observed the hand arthritis side effect also in my resveratrol experiment.

Monday, August 08, 2022

Old hearts learn new tricks

Nusinovich's summary in Science Magazine of work by Lerchenmüller et al.:
Aging-related diseases such as heart failure and other cardiovascular disorders are the leading causes of death in many countries, and they are becoming increasingly common worldwide as the number of older people increases. The ability of the heart to produce new cardiomyocytes decreases with age, which makes it more difficult to repair damage and increases the risk of heart failure. However, a study by Lerchenmüller et al. suggests that exercise may offer some help in this regard even if started late in life. The authors had previously reported that voluntary exercise can stimulate the generation of cardiomyocytes in young adult mouse hearts, and now they have also observed this phenomenon in aged animals.
Here is the results statement of the article:
Cardiomyogenesis was observed at a significantly higher frequency in exercised compared with sedentary aged hearts on the basis of the detection of mononucleated/diploid 15N-thymidine–labeled cardiomyocytes. No mononucleated/diploid 15N-thymidine–labeled cardiomyocyte was detected in sedentary aged mice. The annual rate of mononucleated/diploid 15N-thymidine–labeled cardiomyocytes in aged exercised mice was 2.3% per year. This compares with our previously reported annual rate of 7.5% in young exercised mice and 1.63% in young sedentary mice. Transcriptional profiling of young and aged exercised murine hearts and their sedentary controls revealed that exercise induces pathways related to circadian rhythm, irrespective of age. One known oscillating transcript, however, that was exclusively upregulated in aged exercised hearts, was isoform 1.4 of regulator of calcineurin, whose regulation and functional role were explored further.

Friday, August 05, 2022

Dissecting and improving motor skill acquisition in older adults

 From the introduction of Elvira et al. (open source):

We designed a study intended to identify (i) the main factors leading to differences in motor skill acquisition with aging and (ii) the effect of applying noninvasive brain stimulation during motor training. Comparing different components of motor skill acquisition in young and older adults, constituting the extremes of performance in this study, we found that the improvement of the sequence-tapping task is maximized by the early consolidation of the spatial properties of the sequence in memory (i.e., sequence order), leading to a reduced error of execution, and by the optimization of its temporal features (i.e., chunking). We found the consolidation of spatiotemporal features to occur early in training in young adults, suggesting the emergence of motor chunks to be a direct consequence of committing the sequence elements to memory. This process, seemingly less efficient in older adults, could be partially restored using atDCS by enabling the early consolidation of spatial features, allowing them to prioritize the increase of their speed of execution, ultimately leading to an earlier consolidation of motor chunks. This separate consolidation of spatial and temporal features seen in older adults suggests that the emergence of temporal patterns, commonly identified as motor chunks at a behavioral level, stem from the optimization of the execution of the motor sequence resulting from practice, which can occur only after the sequence order has been stored in memory.
Here is their abstract:
Practicing a previously unknown motor sequence often leads to the consolidation of motor chunks, which enable its accurate execution at increasing speeds. Recent imaging studies suggest the function of these structures to be more related to the encoding, storage, and retrieval of sequences rather than their sole execution. We found that optimal motor skill acquisition prioritizes the storage of the spatial features of the sequence in memory over its rapid execution early in training, as proposed by Hikosaka in 1999. This process, seemingly diminished in older adults, was partially restored by anodal transcranial direct current stimulation over the motor cortex, as shown by a sharp improvement in accuracy and an earlier yet gradual emergence of motor chunks. These results suggest that the emergence of motor chunks is preceded by the storage of the sequence in memory but is not its direct consequence; rather, these structures depend on, and result from, motor practice.

Monday, July 18, 2022

Restoring the aged brain with cerebrospinal fluid.

The transfer of blood plasma from young animals to old animals, has been shown to reverse aging changes in the brain, and now Iram et al. show in mice that infusions of young CSF cerebrospinal fluid (CSF) into the brains of aged animals promote oligodendrogenesis and improve memory function, and that fibroblast growth factor 17 (FGF17) is a key molecule that mediates these effects.
Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.

Friday, July 08, 2022

Stress in older adults accelerates immune system aging.

Seo does a summary article that points to the work of Klopak et al. The Klopak et al. abstract:  

Significance

As the world’s population of older adults increases, understanding disparities in age-related health is essential. Age-related changes in the immune system play a critical role in age-related morbidity and mortality. This study assesses associations between social stress and immunophenotypes as immune age phenotype markers for the first time in a national sample of older US adults. This study helps clarify mechanisms involved in accelerated development of the immune age phenotype, including socioeconomic and lifestyle factors and cytomegalovirus infection and reactivation. This study also identifies important points of intervention that may be useful in addressing inequalities in aging.
Abstract
Exposure to stress is a risk factor for poor health and accelerated aging. Immune aging, including declines in naïve and increases in terminally differentiated T cells, plays a role in immune health and tissue specific aging, and may contribute to elevated risk for poor health among those who experience high psychosocial stress. Past data have been limited in estimating the contribution of life stress to the development of accelerated immune aging and investigating mediators such as lifestyle and cytomegalovirus (CMV) infection. This study utilizes a national sample of 5,744 US adults over age 50 to assess the relationship of social stress (viz., everyday discrimination, stressful life events, lifetime discrimination, life trauma, and chronic stress) with flow cytometric estimates of immune aging, including naïve and terminally differentiated T cell percentages and the ratio of CD4+ to CD8+ cells. Experiencing life trauma and chronic stress was related to a lower percentage of CD4+ naïve cells. Discrimination and chronic stress were each associated with a greater percentage of terminally differentiated CD4+ cells. Stressful life events, high lifetime discrimination, and life trauma were related to a lower percentage of CD8+ naïve cells. Stressful life events, high lifetime discrimination, and chronic stress were associated with a higher percentage of terminally differentiated CD8+ cells. High lifetime discrimination and chronic stress were related to a lower CD4+:CD8+ ratio. Lifestyle factors and CMV seropositivity partially reduced these effects. Results identify psychosocial stress as a contributor to accelerating immune aging by decreasing naïve and increasing terminally differentiated T cells.

Wednesday, July 06, 2022

How stress focuses brain integration

From Wang et al.(open source, with good graphics):
Despite the prevalence of stress, how brains reconfigure their multilevel, hierarchical functional organization in response to acute stress remains unclear. We examined changes in brain networks after social stress using whole-brain resting-state functional MRI (fMRI) by extending our recently published nested-spectral partition method, which quantified the functional balance between network segregation and integration. Acute stress was found to shift the brain into a more integrated and less segregated state, especially in frontal-temporal regions. Stress also stabilized brain states by reducing the variability of dynamic transition between segregated and integrated states. Transition frequency was associated with the change of cortisol, and transition variability was correlated with cognitive control. Our results show that brain networks tend to be more integrated and less variable after acute stress, possibly to enable efficient coping.

Friday, June 24, 2022

Magnetic stimulation of the brain can improve cognitive impairment

An open source article from Liu et al. in the journal Cerebral Cortex reports that repetitive transcranial magnetic stimulation (rTMS) over the bilateral angular gyrus in patients with probable Alzheimer’s disease resulted in up to 8 weeks of significantly improved cognitive function.:
Dementia causes a substantial global economic burden, but effective treatment is lacking. Recently, studies have revealed that gamma-band waves of electrical brain activity, particularly 40 Hz oscillations, are closely associated with high-order cognitive functions and can activate microglia to clear amyloid-β deposition. Here, we found that compared with sham stimulation, applying 40-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) over the bilateral angular gyrus in patients with probable Alzheimer’s disease (AD; n = 37) resulted in up to 8 weeks of significantly improved cognitive function. Power spectral density analysis of the resting-state electroencephalography (EEG) demonstrated that 40-Hz rTMS modulated gamma-band oscillations in the left posterior temporoparietal region. Further testing with magnetic resonance imaging and TMS-EEG revealed the following: 40-Hz rTMS 1) prevented gray matter volume loss, 2) enhanced local functional integration within bilateral angular gyrus, as well as global functional integration in bilateral angular gyrus and the left middle frontal gyrus, 3) strengthened information flow from the left posterior temporoparietal region to the frontal areas and strengthened the dynamic connectivity between anterior and posterior brain regions. These findings demonstrate that modulating gamma-band oscillations effectively improves cognitive function in patients with probable AD by promoting local, long-range, and dynamic connectivity within the brain.

Monday, May 16, 2022

How stress might help reduce dementia and alzheimer’s.

The post today (my 80th birthday) points to experimental results relevant to my interest in not losing my marbles anytime soon. Fauzia points to work by Avezov and collaborators (open source) showing that the accumulation of aggregates of misfolded proteins in the endoplasmic reticulum of brain cells that is associated with dementia and Alzheimer's can be reversed by stressing cells with chemicals or heat, activating molecular chaperones that in turn untangle or remove protein aggregates. How much stress is just enough, but not to much, isn't clear. The abstract of the work:
Protein synthesis is supported by cellular machineries that ensure polypeptides fold to their native conformation, whilst eliminating misfolded, aggregation prone species. Protein aggregation underlies pathologies including neurodegeneration. Aggregates’ formation is antagonised by molecular chaperones, with cytoplasmic machinery resolving insoluble protein aggregates. However, it is unknown whether an analogous disaggregation system exists in the Endoplasmic Reticulum (ER) where ~30% of the proteome is synthesised. Here we show that the ER of a variety of mammalian cell types, including neurons, is endowed with the capability to resolve protein aggregates under stress. Utilising a purpose-developed protein aggregation probing system with a sub-organellar resolution, we observe steady-state aggregate accumulation in the ER. Pharmacological induction of ER stress does not augment aggregates, but rather stimulate their clearance within hours. We show that this dissagregation activity is catalysed by the stress-responsive ER molecular chaperone – BiP. This work reveals a hitherto unknow, non-redundant strand of the proteostasis-restorative ER stress response.