Category Archives: Longevity Medicine

Windowsoffers lots of ways to minimize distractions so it's easier to focus on tasks. You can declutteryour taskbar and simplify the Start menu, use Focus to manage your notifications, and use the Immersive Readerto minimize visual distractions when reading a web page inMicrosoft Edge.

Minimize visual distractions by turning off animations, background images, and more.

Select Start> Settings> Accessibility > Visual effects.

To minimize distractions, do one or more of the following:

To automatically hide the scrollbars in Windows,turn off the Always show scrollbars switch.

To make some window backgrounds more opaque,turn off the Transparency effectsswitch.

If you don't want Windowsto show animations, turn off the Animation effectsswitch.

To define how long notifications are shown, expand theDismiss notifications after this amount of timemenu and select the option you want.

Choose which icons appear on the taskbar and reduce the number of items in view.

Select Start> Settings> Personalization> Taskbar.

SelectTaskbar items and Taskbar corner iconsto expand those sections andturn off the switches for the items you don't want to see on the taskbar.

To select which icons can appear in the taskbar corner, select Taskbar corneroverflow. Turn on the switches for the icons that you want tosee in the taskbar corner. The icons with the switches turned off won't show directly on the taskbarthey'll onlyappear in the taskbar corner overflow menu.

Do not disturballows you to define which notifications you see and hear and when. The rest of the notifications will go to the notification center where you can see them any time.

You can also modify the notifications settings to choose which apps display notifications.

Select Start> Settings> System > Notifications, then adjust the settings.

To see and hear fewer notifications, turn on Do not disturb.

If you want to choose notifications from certain apps, select Set priority notifications. Modify theseoptions to get the notifications you want to see when do not disturb is turned on.

Tip:To quickly switchDo not disturbon, go to the taskbar and select thebattery, network, or volume icon to open the notification center, then turn it on or off.

Select Start> Settings> System > Notifications.

InTurn on do not disturb automatically, selectDuring these times to turn it on.

Choose when do not disturb turns on, turns off, and how often it repeats.

You can also choose the types of tasks that will turn on do not disturb automatically.

If notifications are distracting when they appear on your screen, adjust which apps display notifications and fine-tune how they appear.

Select Start> Settings> System > Notifications.

InNotifications from apps and other senders, turn off the apps you don't wantnotifications from and turn on the apps you do want to get notifications from.

To define where the notifications appear for each app, select a specific app, then change the options as desired.

To read a web page on a simpler and cleaner layout, use the Immersive ReaderinMicrosoft Edge. For more info on theImmersive Reader, go toUse Immersive Reader in Microsoft Edge.

To start using the Immersive Reader, open the web page you want to read inMicrosoft Edge, and then press the function key + F9. Alternatively,select (Enter Immersive Reader) on the address bar.

Tip:If you dont see the (Enter Immersive Reader) icon on the address bar, select the text you want to read, right-click,and selectOpen selection in Immersive Reader.

The page opens on a simpler layout. To change how the page is displayed, review the options on the toolbar at the top of the page. Under Text preferences, for example, you can modify the background color using themesor change the font.

To exit the Immersive Reader, select (Exit Immersive Reader) ontheaddress bar orpress the function key + F9.

Windowsoffers lots of ways to minimize distractions so it's easier to focus on tasks. You can declutteryour taskbar and simplify the Start menu, use Focus assistto manage your notifications, and use the Immersive Readerto minimize visual distractions when reading a web page inMicrosoft Edge.

Minimize visual distractions by turning off animations, background images, and more.

SelectStart , then select Settings > Ease of Access > Display.

Choose from the different options underSimplify and personalize Windows.

Choose which icons appear on the taskbar and reduce the number of items in view.

SelectStart , then select Settings > Personalization > Taskbar .

Under Notification area, choose Select which icons appear on the taskbar.

System icons, like the clock and battery indicator, can also be turned on or off.

Select Start , then select Settings > Personalization .

Under Notification area, choose Turn system icons on or off.

Many apps use Live Tiles to show updates on what's happening in your world, like new email, your next appointment, or the weekend weather. If these animations are distracting, you can turn them off.

Press and hold (or right-click) a tile, and then select More > Turn Live Tile off.

Focus assist (also called quiet hours in earlier versions of Windows 10) allows you to avoid distracting notifications when you need to stay focused.It'sset by default to activate automatically under certain conditions.

Here's how to turn focus assiston or off:

Select the Action Center icon on the taskbar.

Select Focus assist to cycle through the available settings: either Priority only, Alarms only, or Off.(If you don't see the Focus assist tile, you may need to select Expand first.)

Focus assist settings can be editedby selecting Start >Settings> System> Focus assist. Or you cantype Focus assist into the search boxon the taskbar, and then select Focus assist settingsfromthe list of results.

In the Focus assist settings, you can limit late-night notifications using the Automatic rules section. To do that, select During these times and turn on the toggle. Then, selectStart timeorEnd time, picka time, and select the check markto save your changes. You can also choose what days you want to apply the rule, and what types of notifications you'd still like to receive during the times you set.

Open focus assist settings

If notifications are distracting when they appear on your screen, adjust which apps display notifications and fine-tune how they appear. To change notification settings, selectStart , then select Settings > System > Notifications & actions . You can then choose which types of notifications you want to see.

For a clean and simple layout, use Reading view in the Microsoft Edge browser address bar to bring whatever you're reading front and center. After you open an article, you'll see abook icon on the right side of your browser. When you select it, you'll be in reading view.

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Make it easier to focus on tasks - Microsoft Support

Surface Laptop 4 13.5 AMD Ryzen 5 Microsoft Surface Edition processor 8 GB RAM

Up to 19 hours of battery life based on typical Surface device usage

Testing conducted by Microsoft in February 2021 using preproduction software and preproduction 13.5 AMDRyzen5 Microsoft SurfaceEdition processor, 8GB RAM device. Testing consisted of full batterydischargewith a mixture of active use and modern standby. The active use portion consists of (1) a web browsing test accessing 8 popular websites over multiple open tabs, (2) a productivity test utilizing Microsoft Word, PowerPoint, Excel, and Outlook, and (3) a portion of time with the device in use with idle applications. All settingsweredefault except screen brightness was set to 150nits with Auto-Brightness disabled.Wi-Fi was connected toanetwork.Battery life varies significantly with settings,usage,and other factors.

Surface Laptop 4 15 AMD Ryzen 7 Microsoft Surface Edition processor 8 GB RAM

Up to 17.5 hours of battery life based on typical Surface device usage

Testing conducted by Microsoft in February 2021 using preproduction software and preproduction 15 AMD Ryzen 7 Microsoft Surface Edition processor, 8GB RAM device. Testing consisted of full battery discharge with a mixture of active use and modern standby. The active use portion consists of (1) a web browsing test accessing 8 popular websites over multiple open tabs, (2) a productivity test utilizing Microsoft Word, PowerPoint, Excel and Outlook, and (3) a portion of time with the device in use with idle applications. All settings were default except screen brightness was set to 150nits with Auto-Brightness disabled. Wi-Fi was connected to a network. Battery life varies significantly with settings, usage and other factors.

Surface Laptop 4 13.5 Intel Core i5 512GB, 8 GB RAM

Up to 17 hours of battery life based on typical Surface device usage

Testing conducted by Microsoft in February 2021 using preproduction software and preproduction 13.5 Intel Core i5, 512GB, 8 GB RAM device. Testing consisted of full battery discharge with a mixture of active use and modern standby. The active use portion consists of (1) a web browsing test accessing 8 popular websites over multiple open tabs, (2) a productivity test utilizing Microsoft Word, PowerPoint, Excel and Outlook, and (3) a portion of time with the device in use with idle applications. All settings were default except screen brightness was set to 150nits with Auto-Brightness disabled. Wi-Fi was connected to a network. Battery life varies significantly with settings, usage and other factors.

Surface Laptop 4 15 Intel Core i7 512GB, 16 GB RAM

Up to 16.5 hours of battery life based on typical Surface device usage

Testing conducted by Microsoft in February 2021 using preproduction software and preproduction 15 Intel Core i7, 512GB, 16 GB RAM device. Testing consisted of full battery discharge with a mixture of active use and modern standby. The active use portion consists of (1) a web browsing test accessing 8 popular websites over multiple open tabs, (2) a productivity test utilizing Microsoft Word, PowerPoint, Excel, and Outlook, and (3) a portion of time with the device in use with idle applications. All settings were default except screen brightness was set to 150nits with Auto-Brightness disabled. Wi-Fi was connected to a network. Battery life varies significantly with settings, usage and other factors.

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Surface battery testing and estimated performance

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with-and perhaps without-impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD. The quality of dietary protein may also play a role in kidney health. Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies, including the Singapore Chinese Health Study. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. In light of such findings, adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease. Given the possibility of residual confounding within some observational studies and the conflicting evidence from previous trials, long-term studies including those with large sample sizes are warranted to better ascertain the effects of high protein intake on kidney health.

Keywords: chronic kidney disease; glomerular hyperfiltration; high protein diet; nutrition; proteinuria.

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The Effects of High-Protein Diets on Kidney Health and Longevity

9/7/2022

PITTSBURGHToday in Nature, University of Pittsburgh researchers describe for the first time a pathway by which cells repair damaged lysosomes, structures that contribute to longevity by recycling cellular trash. The findings are an important step towards understanding and treating age-related diseases driven by leaky lysosomes.

Lysosome damage is a hallmark of aging and many diseases, particularly neurodegenerative disorders such as Alzheimers, said lead author Jay Xiaojun Tan, Ph.D., assistant professor of cell biology at Pitts School of Medicine and member of the Aging Institute, a partnership between Pitt and UPMC. Our study identifies a series of steps that we believe is a universal mechanism for lysosomal repair, which we named the PITT pathway as a nod to the University of Pittsburgh.

As the cells recycling system, lysosomes contain potent digestive enzymes that degrade molecular waste. These contents are walled off from damaging other parts of the cell with a membrane that acts like a chain link fence around a hazardous waste facility. Although breaks can occur in this fence, a healthy cell quickly repairs the damage. To learn more about this repair process, Tan teamed up with senior author Toren Finkel, M.D., Ph.D., director of the Aging Institute and distinguished professor of medicine at Pitts School of Medicine.

First, Tan experimentally damaged lysosomes in lab-grown cells and then measured the proteins that arrived on the scene. He found that an enzyme called PI4K2A accumulated on damaged lysosomes within minutes and generated high levels of a signaling molecule called PtdIns4P.

PtdIns4P is like a red flag. It tells the cell, Hey, we have a problem here, said Tan. This alert system then recruits another group of proteins called ORPs.

ORP proteins work like tethers, Tan explained. One end of the protein binds to the PtdIns4P red flag on the lysosome, and the other end binds to the endoplasmic reticulum, the cellular structure involved in synthesis of proteins and lipids.

The endoplasmic reticulum wraps around the lysosome like a blanket, added Finkel. Normally, the endoplasmic reticulum and lysosomes barely touch each other, but once the lysosome was damaged, we found that they were embracing.

Through this embrace, cholesterol and a lipid called phosphatidylserine are shuttled to the lysosome and help patch up holes in the membrane fence.

Phosphatidylserine also activates a protein called ATG2, which acts like a bridge to transfer other lipids to the lysosome, the final membrane repair step in the newly described PITT or phosphoinositide-initiated membrane tethering and lipid transport pathway.

Whats beautiful about this system is that all of the components of the PITT pathway were known to exist, but they werent known to interact in this sequence or for the function of lysosome repair, said Finkel. I believe these findings are going to have many implications for normal aging and for age-related diseases.

The researchers suspect that in healthy people, small breaks in the lysosome membrane are quickly repaired through the PITT pathway. But if the damage is too extensive or the repair pathway is compromised due to age or disease leaky lysosomes accumulate. In Alzheimers, leakage of tau fibrils from damaged lysosomes is a key step in progression of the disease.

When Tan deleted the gene encoding the first enzyme in the pathway, PI4K2A, he found that tau fibril spreading increased dramatically, suggesting that defects in the PITT pathway could contribute to Alzheimers disease progression. In future work, the researchers plan to develop mouse models to understand whether the PITT pathway can protect mice from developing Alzheimers disease.

This research was supported by the National Institutes of Health (P30AG024827, R01HL142663, R01HL142589, U54AG075931 and K01AG075142) and the UPMC Competitive Medical Research Fund.

PHOTO INFO: (click image(s) for high-res version(s))

Top:

CREDIT: UPMC

CAPTION: Jay Xiaojun Tan, Ph.D.

Middle:

CREDIT: UPMC

CAPTION: Toren Finkel, M.D., Ph.D.

Bottom:

CREDIT: Jay Xiaojun Tan

CAPTION: Fluorescence microscopy image showing the endoplasmic reticulum network (green) wrapping around damaged lysosomes (red). The cell nucleus is shown in blue.

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PITT Pathway: Pitt Scientists Discover How Cells Repair Longevity ...

Additionally, Nearly 140 Global Innovators Awarded for Projects aimed at improving Healthy Longevity

The National Academy of Medicines (NAM) Healthy Longevity Global Competition is pleased to announce the extension of its international Catalyst Awards through 2025, adding three annual cycles to seed innovative ideas. Focusing on helping accelerate research and entrepreneurism to foster potential breakthroughs in healthy longevity, the Global Competition is a multiyear, multi-phase international competition designed with the aim to help advance bold, novel ideas with the potential to dramatically improve health as people age. The Global Competition consists of three progressive phases during which innovators have the opportunity to compete for increasingly larger awards at the Catalyst, Accelerator, and Grand Prize levelsthe latter up to $5 million.

The Global Competition, along with its sister program the Global Roadmap for Healthy Longevity, are part of a larger initiative to fuel a worldwide movement to help improve physical, mental, and social well-being for people as they age, known as the Healthy Longevity Global Grand Challenge. Unique to the Global Competition component in particular is the emphasis on bold, new ideas with the potential for big impactin disease prevention, mobility, functionality, social connectedness, the biology of aging, and more.

Weve been pleased to see the momentum, excitement, and innovative research that the Grand Challenge has generated in the field of healthy longevity since its inception, said NAM President Victor J. Dzau. This award competition program has attracted widespread interest from global innovators to explore novel ideas that may ultimately improve health throughout the lifespan, fostering opportunities for meaningful engagement at all stages of life. We are so pleased that our global collaborators enthusiastically support the extension of the Catalyst Awards competition through 2025 which would sustain the momentum and trajectory of this important movement.

Since its launch in October 2019, the Global Competition has brought together eleven global collaborators representing over 50 countries and territories. The NAM founded the competition and coordinates among a network of global collaborators, each sponsoring a Catalyst Award competition, while also administering a U.S.-based competition. Catalyst Awards are worth $50,000 USD. To date, the NAM and its global collaborators have issued more than $23.5 million in award funding to nearly 430 Catalyst and 13 Accelerator Awardees worldwide.

In addition to announcing the extension of the Catalyst Awards today, the NAM and its global collaborators announced the winners of the 2022 Healthy Longevity Catalyst and Accelerator Awards at the annual Global Innovator Summit. This year, innovators around the world submitted more than 1,100 applications, with over 470 of those from U.S.-based applicants. Ultimately, the NAM selected 25 Catalyst Awardees in 2022. They include:

The U.S.-based awards are sponsored by Johnson and Johnson Innovation, Bia Echo & Yun Family Foundations, and the NextFifty Initiative, which support of the Healthy Longevity Global Competition in the quest to find bold and transformative innovations to extend human health and function later in life.

Other organizations issuing Catalyst Awards in 2022 include the Academia Sinica of Taiwan; Chinese Academy of Medical Sciences; EIT Health of the European Union; Agency for Medical Research and Development of Japan; Ministry of Health and National Research Foundation of Singapore; National Agency for Research and Development of Chile; Research Grants Council of the Hong Kong Special Administrative Region, China; and UK Research and Innovation.

As Catalyst Awardees and Finalists projects progress, they become eligible to apply for support in the second phase of the competition, the Accelerator Phase. The three global Accelerator sponsorsJohnson and Johnson Innovation, Eisai, and the European Investment Bank (in partnership with kENUP Foundation)each administer awards.

This year, Johnson and Johnson Innovation announced the second cohort of awardees from its NAM Healthy Longevity QuickFire Challenge (Accelerator Awards). Each awarded project team will have the opportunity to receive funding and mentorship from experts across The Johnson and Johnson Family of Companies with the aim to help advance their Catalyst Award-winning work further. Awarded projects are listed below.

From the 2021 International Catalyst Award Winners:

From the 2020 International Catalyst Award Winners:

As part of the Global Competitions commitment to share knowledge and stimulate an entire field by not only rewarding innovative ideas but also sharing those ideas with the world, project summaries are available atwww.healthylongevitychallenge.org.

The final phase of the global competition, the Grand Prize, is anticipated in 2025 and will award one or more prizes of $5 million each for the achievement of a potentially transformative innovation that extends healthspan. Learn more about the NAMs Global Grand Challenge Competition and sign up for updates.

The Healthy Longevity Global Competition is sponsored by Anthony J. Yun and Kimberly A. Bazar, the Bia-Echo Foundation, the John A. Hartford Foundation, John and Valerie Rowe, Johnson & Johnson Innovation, NextFifty Initiative, United Therapeutics Corp, and the Yun Family Foundation, in addition to commitments from the global collaborators of the Catalyst Phase and organizations sponsoring the Accelerator Phase.

TheNational Academy of Medicine, established in 1970 as the Institute of Medicine, is an independent organization of eminent professionals from diverse fields including health and medicine; the natural, social, and behavioral sciences; and beyond. It serves alongside theNational Academy of Sciencesand theNational Academy of Engineeringas an adviser to the nation and the international community. Through its domestic and global initiatives, the NAM works to address critical issues in health, medicine, and related policy and inspire positive action across sectors.The NAM collaborates closely with its peer academies and other divisions within theNational Academies of Sciences, Engineering, and Medicine.

For questions, contact:Dana Korsen, Media Relations ManagerOffice of News and Public Information202-334-2138; e-mailnews@nas.edu

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NAM Extends Catalyst Phase of the Healthy Longevity Global Competition Through 2025 at Global Innovator Summit - National Academy of Medicine

Summary: Researchers have designed a new model of life expectancy thats based less on disease diagnosis, and more on other factors including cholesterol levels and lifestyle.

Source: Duke University

A new model to predict the life expectancy of older people relies less on their specific disease diagnoses and more on factors such as the ability to grocery shop, the amount of certain small cholesterol particles circulating in their blood, and whether they never or only occasionally smoked.

The findings from a study led by Duke Health researchers provide a way to predict whether a person over the age of 70 is likely to live two, five or 10 years. The markers may be obtained during a doctor visit, so they could be a useful guide for clinical care.

This study was designed to determine the proximal causes oflongevitythe factors that portend whether someone is likely to live two more years or 10 more years, said Virginia Byers Kraus, M.D., Ph.D., professor in the departments of Medicine, Pathology and Orthopedic Surgery at Duke University School of Medicine and lead author of the study appearing online in the journaleBioMedicine.

Properly applied, these measures could help determine the benefits and burdens of screening tests and treatment for older people, Kraus said.

Kraus and colleagues launched their inquiry at an opportune time, having been directed to a cache of 1,500blood samplesfrom a 1980slongitudinal studythat enrolled older people.

The banked samples had been drawn in 1992 when participants were at least 71 years old and then stored at the NIH. They were scheduled for destruction, but the researchers arrived in time to transfer them to Duke for analysis.

The blood samples had the additional fortuitous feature of being drawn at a time that preceded the widespread use of medications such as statins, which could have skewed the results. Moregood luck: study participants had been followed for several years and had filled out questionnaires about their health histories and habits.

Capitalizing on all the features of the older study, the researchers were able to apply current sophisticated analytical tools. Led by Constantin Aliferis and Sisi Ma at the University of Minnesota, the researchers were able to delve into health factors to identify a core set of 17 predictive variables that have a causal impact on longevity.

The analysis found that a leading factor associated with longevity across each of the studys benchmarkstwo-, five- and 10-years after participants had their blood drawnwas physical function, which was defined as an ability to go grocery shopping or perform housecleaning chores. Surprisingly, having cancer or heart disease was not among the main predictors.

Forolder peopleliving two years beyond the time their blood had been drawn, the leading factor associated with longevity was having an abundance of high-density lipoprotein (HDL) cholesteroland not just any HDL lipids, but high volumes of very small HDL particles.

This was especially surprising, Kraus said. We hypothesize that these very small HDL particles are the size that is best at scavenging and clearing endotoxin, a potent inflammation-causing molecule from gut microbes, from the circulation [VBKMP1] .

The small particle may also be best able to get into the nooks and crannies of cells to remove the bad cholesterol, so having more of them could provide this protective benefit.

At five years beyond the originalblooddraw, just being of a younger age was predictive of longevity, along with cognitive function. And among the longest survivorsthose living 10 yearsthe best predictor was a persons smoking history, with non-smokers faring best.

These measures clarify and enrich our understanding of mechanisms underlying longevity and could point to appropriate tests and potential interventions, Kraus said.

She said the next stage of research is to use additional analytical tools to improve the predictivity and identify potential targets for therapies.

Author: Alexis PorterSource: Duke UniversityContact: Alexis Porter Duke UniversityImage: The image is in the public domain

Original Research: Open access.Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults by Virginia Byers Kraus et al. eBioMedicine

Abstract

Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults

The hard endpoint of death is one of the most significant outcomes in both clinical practice and research settings. Our goal was to discover direct causes of longevity from medically accessible data.

Using a framework that combines local causal discovery algorithms with discovery of maximally predictive and compact feature sets (the Markov boundaries of the response) and equivalence classes, we examined 186 variables and their relationships with survival over 27 years in 1507 participants, aged 71 years, of the longitudinal, community-based D-EPESE study.

As few as 8-15 variables predicted longevity at 2-, 5- and 10-years with predictive performance (area under receiver operator characteristic curve) of 076 (95% CIs 069, 083), 076 (072, 081) and 066 (061, 071), respectively. Numbers of small high-density lipoprotein particles, younger age, and fewer pack years of cigarette smoking were the strongest determinants of longevity at 2-, 5- and 10-years, respectively. Physical function was a prominent predictor of longevity at all time horizons. Age and cognitive function contributed to predictions at 5 and 10 years. Age was not among the local 2-year prediction variables (although significant in univariable analysis), thus establishing that age is not a direct cause of 2-year longevity in the context of measured factors in our data that determine longevity.

The discoveries in this study proceed from causal data science analyses of deep clinical and molecular phenotyping data in a community-based cohort of older adults with known lifespan.

NIH/NIA R01AG054840, R01AG12765, and P30-AG028716, NIH/NIA Contract N01-AG-12102 and NCRR 1UL1TR002494-01.

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How Long Older Adults Will Live Comes Down to 17 Often Surprising Factors - Neuroscience News