As I wrote in SUPER AGERS, the immune system is the key to modulating our aging process and the opportunity to extend healthspan. Today @NatureAging 7 new articles, summarized here, that reinforce its central role
nature.com/articles/s4358… Inflammaging: with aging comes untoward inflammation, a summary graphic
nature.com/articles/s4358…

The new special issue @ScienceMagazine features Immunity with 4 outstanding review papers, 5★
Our immune system over the lifespan, sex differences, influence on physiology, and host antiviral defenses science.org/toc/science/cu… Our immune system as we age: the path to immunosenesence and inflammaging
science.org/doi/10.1126/sc…

We've learned a lot more about the principal drivers of age-related diseases in the past few weeks. And that leads to a unified model to pull it all together. (open-access) I review 4 new reports, summarized here:
1. The proteins from senescent cells predict age-related clinical outcomes
2. A new epigenetic age clock connects the dots between aging, the immune system, inflammation and lifestyle factors
3. People with a fast pace of aging had an increased risk of cognitive impairment, age-related diseases, disability, and mortality
4. The Importance of “Immune Resilience” for Healthspan

Most people haven’t heard of this test, which is available in the US. It accurately predicts Alzheimer’s (not just if there’s a risk, but when). It is favorably affected by exercise and likely many other lifestyle factors.
Here’s (almost) everything we know about it. In Ground Truths (link in my profile d/t X-suppression) Here's the response to exercise

A major @Nature paper this week found a significant decline in dementia after an outdated Shingles vaccine.
I've reviewed the study and many other relevant ones in a new Ground Truths (link in profile) A Table from the post

The vaccine against Shingles helps protect against dementia, results of a natural experiment, adding to prior evidence
"implications are profound"
New @Nature
nature.com/articles/s4158…
nature.com/articles/d4158…

https://x.com/EricTopol/status/1901957986727117069

Of >105,000 participants with 30-year follow-up, only 9.3% achieved healthy aging (age 70, w/o any chronic diseases). Their diet was significantly associated with this outcome🧵 @NatureMedicine These are the specific foods that were linked with healthy aging and other outcomes. Green-favorable; Red-unfavorable

A paper on microplastics accumulating in the brain was just published @NatureMedicine, open-access
I review the background and major implications in a new Ground Truths edition (link in my profile)nature.com/articles/s4159…
The human brain:
—had 7-30 times more accumulation of microparticles (MPs) than the liver or kidney (organs with previously documented high propensity)
—from people with dementia had 5X accumulation of MPs compared with non-dementia
—there was a marked increase of accumulation over recent years

Three new @NEJM reports on #H5N1 today
1. An overview by @MichaelGIsonMD and @DrJeanneM
"urgent need for vigilant surveillance of emerging mutations and assessment of the threat of human-to-human transmission"
2. Report of the 13-year-old Canadian girl who developed acute respiratory failure. Sequence of her H5N1 revealed 3 mutations that may be linked to higher virulence and adaptation to human cell binding

We're learning how to control the immune response, like a rheostat, even in the brain. Implications for understanding the basis and potential treatment of autoimmune conditions like multiple sclerosis, #LongCovid, #MECFS, and brain cancer.
A brief review of 6 recent, important reports
in the new Ground Truths, open-access Such as Programming T cells with brain-specific proteins and payloads
@ScienceMagazine science.org/doi/10.1126/sc…

New @NEJM
A whopping (~90%) reduction of progression to Type 2 diabetes with tirzepatide (GLP-1 drug, dual receptor) vs placebo in a randomized trial of >2,500 participants with obesity, absolute reduction of 10/100 treated

by @AniaJastreboff and collaboratorsnejm.org/doi/full/10.10… In other GLP-1 new publications today
—Country-wide Sweden reduced hospitalizations for alcohol or substance abuse with these drugs
jamanetwork.com/journals/jamap… @JAMAPsych
—Concerns about discontinuation
jamanetwork.com/journals/jama/… @JAMA_current

A dedicated issue of @ScienceTM on #LongCovid
—Sex-specific differences, with perspective by @VirusesImmunity and @SilvaJ_C
—Insights for therapies @AndreaCoxMDPhD
—Deconvoluting "Osler's Web" @MichaelPelusoMD @DeeksSteven @DrMaureenHanson @SaydahSharon
—+RECOVER Trial, Lyme disease

science.org/toc/stm/16/773

An elegant @Nature study by @AkassoglouLab has illuminated our understanding of the role of fibrin (component of blood clots), #SARSCoV2, and brain inflammation in Covid and #LongCovid.
This discovery and more in the new Ground Truths podcast, with transcript, key figures (such as as the one below) and citations. Open-access. Link in my profile.
A clip from our conversation. Unknowingly, @AkassoglouLab was gearing up for understanding this complex pathophysiology for many years before Covid hit

Covid and increased risk of major adverse cardiovascular events (MACE) 3-years out

2-fold increased for any severity of Covid
~4-fold increase for Covid requiring hospitalization
"a coronary artery disease equivalent"
interaction with non-O blood types
@uk_biobankahajournals.org/doi/10.1161/AT… "A major finding from our analyses was that the risk
of MACE among the subset of hospitalized COVID-
19 cases without known CVD (ie, primary prevention
patients) was comparable to (or even slightly higher than) the risk in patients with CVD, PAD, or diabetes but without COVID-19."

New US Covid genomic surveillance
The KP.3.1.1 variant is on the move to become dominant, more of a challenge to our immune response than KP.3 and prior variants (especially without new KP.2 booster when we need it for high-risk individuals) It's the deletion 31/31 that makes the KP.3.1.1 spike different, but otherwise 2 mutations away from KP.2 (R346T and Q493E)

The new boosters (vs. KP.2) should be available the first week of September. It takes ~90 days make them from the FDA decision on June.

But it didn't have to be that way.......1/5nbcnews.com/health/health-… We've known about KP.3's marked growth advantage since April and could have made the call then to make the new booster. That would have been aligned well with the current wave (available in July) 2/5 erictopol.substack.com/p/are-we-flirt…

New CDC genomic data shows continued rise of the KP.3 variant that accounts for 1 of 3 Covid cases.
LB.1 is gaining, too, as JN.1 fades away This variant growth advantage plot by @BenjMurrell (H/T @siamosolocani) shows why this is the case. Note KP.3 is the one at far left w/ almost 3-fold advantage to JN.1.
Reinforces why the decision to develop the KP.2 vaccine booster (instead of JN.1) was a good one

The connection between #SARSCoV2 and neurodegeneration
@TheLancetNeuro
Quotes below:
1. SARS-CoV-2 infection should be considered as a risk factor for Alzheimer’s disease, even though the distinction between causation versus disease acceleration is not clear.thelancet.com/journals/laneu… 2. Inflammation in patients with COVID-19, and controlled experiments show prolonged neuro-inflammation after mild SARS-CoV-2 infection
in macaques.

The FLiRT variant KP.2 begins its takeover for Covid cases in the US, now accounting for 1 in 4 cases
covid.cdc.gov/covid-data-tra…
I've reviewed the FLiRT variants and their implications in a Ground Truths (link in profile)

Breaking down the risks and benefit for lecanemab, the amyloid beta-directed antibody vs Alzheimer's drug approved @US_FDA last year. It doesn't look good.

@AnnalsofIM acpjournals.org/doi/10.7326/M2…
A new systematic review of these antibodies looks even worse @AnnFamMed doi.org/10.1370/afm.30…

My oped on the JN.1 variant and the 2nd biggest US wave of infections (after Omicron) since the pandemic began
@latimes @latimesopinion #LongCovid latimes.com/opinion/story/…
Recent @CDCgov #SARSCoV2 wastewater data for current wave (vs Omicron Jan 2022 and subsequent waves), graph by @luckytran