What are the opening hours?

Monday 9am - 5pm Wednesday 9am - 5pm Friday 9am - 5pm Saturday 9am - 5pm

Anil Bajnath, MD, 7030 Hi Tech Drive Suite 101, Hanover, MD (2026)

06/01/2026

There is a risk factor for chronic kidney disease that most clinicians are not asking about in the clinical encounter: the air their patients breathe every day.

A landmark review just published in Nature Reviews Nephrology by Ahn, Yun, Kim, Al-Aly, Bell, and Lee brings together the epidemiological and experimental evidence linking atmospheric stressors — ambient air pollution, wildfire smoke, and extreme temperatures — to acute kidney injury, chronic kidney disease, and kidney failure. The scope of the evidence is striking.

Multiple large cohort studies, including analyses of over two million US veterans and over 60 million Medicare enrollees, have reported consistent associations between long-term exposure to PM2.5 and a range of adverse kidney outcomes: incident CKD, eGFR decline, progression to kidney failure, and AKI-related hospitalization and death. These associations have been replicated across Europe, Asia, and North America, and observed at concentrations below current WHO air quality guidelines. Gaseous pollutants including nitrogen dioxide, ozone, and carbon monoxide have also been independently associated with kidney-related outcomes across multiple study designs and populations.

The mechanisms are not speculative. Inhaled PM2.5 generates reactive oxygen species directly and through NADPH oxidase activation, sensitizes proximal tubular epithelial cells to ischaemia-reperfusion injury, activates the NLRP3 inflammasome driving renal inflammation and fibrosis, and contributes to intraglomerular hypertension and glomerulosclerosis through both haemodynamic and non-haemodynamic pathways.

Extreme heat adds further insult through dehydration-driven fructokinase activation, uric acid generation, and extracellular volume depletion — all converging on tubular injury and GFR decline.

Wildfire smoke, with its higher free-radical and carbonaceous particulate content compared to urban ambient pollution, represents an emerging exposure of growing concern. A 2025 study of haemodialysis patients during the 2023 Canadian wildfires found an 18% increase in same-day all-cause mortality associated with smoke plume presence, and a 139% increase associated with a 10 µg/m³ increase in wildfire-related PM2.5.

The review also identifies populations at amplified risk: the elderly, children, pregnant women, and those with diabetes, hypertension, obesity, or pre-existing kidney disease. These are precisely the patients already in functional medicine and nephrology practices — and their environmental exposures are rarely part of the clinical picture.

This is the paper that makes the case for including atmospheric stressor assessment in the nephrology workup. Read it in full.

DOI: https://doi.org/10.1038/s41581-026-01073-1

05/26/2026

The gut microbiome has never been more clinically relevant — but not for the reason most practitioners assume.

The prevailing conversation about the microbiome focuses on which bacterial species are present or absent. A comprehensive review just published in Nature Reviews Gastroenterology & Hepatology argues that this framing misses the mechanism entirely.

The real determinants of microbiome–host crosstalk are microbial enzymes — thousands of them — that actively modify bile acids, steroid hormones, neurotransmitters, immunoglobulins, nutrients, and the drugs your patients take every day.

The review introduces and systematically develops the concept of microbiota–host isozymes: gut microbial enzymes that perform the same biochemical function as host enzymes but differ in protein structure, remain unaffected by drugs targeting their human counterparts, and vary substantially between individuals.

The flagship example is Bacteroides-derived DPP4, which degrades the incretin hormone GLP-1 in the gut — exactly as host DPP4 does — yet sitagliptin, the standard human DPP4 inhibitor, cannot inhibit the microbial version. The review's authors, writing from Peking University, argue this may explain why some patients with type 2 diabetes respond robustly to gliptin therapy while others do not.

The clinical reach of microbial enzymes extends further. Bile salt hydrolase activity has been mechanistically linked to polycystic o***y syndrome and to the metabolic benefits of metformin. Gut bacterial tyrosine decarboxylase converts levodopa into dopamine before it reaches the brain, reducing the efficacy of Parkinson's disease treatment. Microbial β-glucuronidase reconverts an inactivated chemotherapy metabolite back to its toxic form in the intestinal lumen, causing the severe diarrhea associated with irinotecan.

Microbial enzymes synthesizing trimethylamine from dietary choline are mechanistically implicated in cardiovascular disease risk. The same microbiota converts glucosinolates from cruciferous vegetables into chemoprotective isothiocyanates.

The review also maps the full landscape of how these enzymes are discovered — from classical biochemistry and functional metagenomics to AI-assisted platforms now capable of predicting novel bile acid metabolic enzymes at scale — and outlines therapeutic strategies ranging from targeted small-molecule inhibitors to engineered live biotherapeutics.

For those practicing at the intersection of functional and precision medicine, this paper provides the mechanistic foundation for what many clinicians have observed empirically: the microbiome shapes drug response, hormone metabolism, and metabolic health through molecular machinery that compositional testing alone cannot capture.

This is the paper to read.
DOI: https://doi.org/10.1038/s41575-026-01195-8

05/21/2026

A paper just published in Nature Aging answers a question that has sat unresolved in immunology for years: can macrophages undergo true, irreversible cellular senescence — and if so, do they matter clinically?

The answer, based on multi-omic characterization of primary mouse and human macrophages, appears to be yes on both counts. Salladay-Perez and colleagues identified a population of p21⁺TREM2⁺ senescent macrophages that are mechanistically distinct from classical inflammatory or anti-inflammatory macrophage states. These cells exhibit permanent cell-cycle arrest, a robust senescence-associated secretory phenotype, lipid droplet accumulation, and elevated type I interferon signaling driven by cytosolic mitochondrial DNA — a process the authors traced to upregulation of CMPK2 and activation of the cGAS-STING pathway.

One of the most clinically significant findings is that p16, the marker most commonly used to identify senescent cells in aging research, was paradoxically downregulated or unchanged in senescent macrophages in both mouse and human models. p21 proved to be the more reliable marker. This distinction matters enormously for any clinical or research application that relies on p16-based reporter systems to detect or target senescent immune populations.

The study also establishes cholesterol as a driver of macrophage senescence. Excess cholesterol ester loading via acetylated LDL was sufficient to induce a senescent, foam cell-like state characterized by TREM2 and p21 upregulation, SA-β-galactosidase activity, cell-cycle arrest, and SASP activation — without any exogenous DNA damage. In aged mouse livers, p21⁺F4/80⁺ macrophages rose from roughly 5% to 50% of the total macrophage pool. In human cirrhotic liver tissue, the macrophage senescence gene signature was most strongly enriched in TREM2⁺ scar-associated macrophages.

The therapeutic arm of the study is particularly striking. The senolytic ABT-263 selectively eliminated senescent macrophages — sparing M1 and M2 populations — and reduced hepatic steatosis, systemic inflammatory markers, and liver NAD⁺ decline in both aged mice and a diet-induced metabolic liver disease model. Liver NAD⁺ levels increased by 30% following senolytic treatment, consistent with the known role of CD38-expressing senescent cells in tissue NAD⁺ degradation.

For anyone working at the intersection of metabolic health, biological aging, and chronic inflammation, this paper offers one of the most mechanistically rigorous accounts yet of how the immune system becomes a source of its own pathology with age. The data suggest that macrophage senescence is not incidental to metabolic liver disease — it may be central to it.

The full paper is worth reading carefully, particularly the multi-omic datasets and the human cirrhosis single-cell analysis.

DOI: https://doi.org/10.1038/s43587-026-01101-6

05/20/2026

If you carry APOE4, your risk of Alzheimer's disease is two to three times higher than average — up to twelvefold if you carry two copies.

If you carry APOE2, your risk is significantly lower, and your age of onset is delayed even in families with high-penetrance mutations. The question that has remained largely unanswered is why — and whether the two alleles work through the same biological system in opposite directions, or through fundamentally different mechanisms.

A landmark study published in Nature Aging (Lu et al., May 2026) answers that question with the most comprehensive cross-platform proteomic analysis of APOE isoforms ever conducted. Spanning five cohorts — GNPC, BioFINDER-2, ADNI, UK Biobank, and PPMI — and more than 11,000 individuals across plasma and cerebrospinal fluid, the study systematically mapped how APOE2 and APOE4 shape the circulating proteome before and after the onset of amyloid pathology and clinical disease.

The APOE2 findings are particularly striking. Over 73% of APOE2-associated protein changes were already detectable in cognitively unimpaired individuals, stable across age groups from early adulthood to late life, and largely independent of AD diagnosis.

The key upstream mediators of APOE2's protective effect — SNAP23, APOB, WARS2, and PCLAF — point to mechanisms involving endocytic trafficking, lipid metabolism, mitochondrial translation, and DNA repair. Together they suggest that APOE2 establishes a constitutive biological resilience program early in life that actively suppresses stress and inflammatory signaling and resists the pathological remodeling that characterizes Alzheimer's disease progression.

APOE4 tells a different story. While some APOE4-associated protein changes appear early and independently of amyloid, the majority of the APOE4 proteomic signature is shaped by downstream pathology. Only a small number of proteins — including SPC25, S100A13, and TBCA — showed evidence of upstream mediation, meaning APOE4 itself drives their changes rather than inheriting them from amyloid accumulation. The rest largely reflect vascular, glial, immune, and proteostatic dysfunction that emerges as the disease unfolds.

Critically, APOE2 and APOE4 are not simply mirror images of each other. They operate through largely non-overlapping sets of mediator proteins. A small group of proteins — VPS29, PHGDH, and FOXO1 — are oppositely regulated by the two alleles and may represent molecular switch nodes that drive divergent biological trajectories toward resilience or vulnerability. These allele-specific upstream proteins are detectable before amyloid positivity, supported by Alzheimer's GWAS genetic evidence, and show spatial co-expression with APOE in the human brain — making them credible candidates for early biomarker development and allele-targeted preventive intervention.

For anyone thinking about brain longevity and Alzheimer's prevention, this paper reframes the conversation. Genotype-informed prevention will require separate therapeutic logic for APOE2 carriers and APOE4 carriers — not simply more or less of the same approach.

Read the full paper here: https://doi.org/10.1038/s43587-026-01123-0

05/19/2026

A large, rigorous randomized controlled trial has just produced the strongest evidence to date that a simple daily multivitamin can meaningfully slow biological aging — particularly in people whose biological age is already running ahead of their chronological age.

The COSMOS ancillary study, published in Nature Medicine (March 2026), examined the effect of two years of daily multivitamin-multimineral supplementation on five DNA methylation-based epigenetic aging clocks in 958 older adults with a mean age of 70 years. This was a prespecified, double-blind, placebo-controlled analysis embedded within one of the largest prevention trials ever conducted. Compliance exceeded 91%.

The epigenetic clocks measured included first-generation clocks predicting chronological age and second-generation clocks — GrimAge and PhenoAge — that predict health span and mortality risk.

The results were clock-specific and clinically informative. The first-generation lifespan clocks showed no significant effect from multivitamin use. The second-generation health-span clocks — those most strongly associated with morbidity, frailty, and all-cause mortality — showed significant slowing: a yearly reduction in PCGrimAge of 0.113 years and PCPhenoAge of 0.214 years compared to placebo.

DunedinPACE, the pace-of-aging clock, significantly increased in the placebo group but remained stable in the multivitamin group, though the between-group difference did not reach statistical significance.

The most striking finding is the subgroup interaction. Among participants with accelerated biological aging at baseline — those whose epigenetic age already exceeded their chronological age — the multivitamin reduced the yearly rate of GrimAge increase by 0.236 years, versus a non-significant 0.013 years among those without baseline age acceleration.

This interaction was statistically significant. In an exploratory analysis of nutritional biomarkers, lower baseline nutrient levels were associated with greater biological age acceleration, and the multivitamin significantly raised folate and lutein specifically among those with accelerated aging — pointing toward micronutrient insufficiency as a plausible driver of the excess aging signal, and its correction as the mechanism of benefit.

Component analysis of GrimAge further revealed that the multivitamin significantly improved DNA methylation-based measures of telomere length, beta-2 microglobulin, cystatin C, and GDF-15 — biomarkers spanning cellular senescence, immune aging, renal function, and mitochondrial stress. Cocoa extract, despite showing cardiovascular mortality benefits elsewhere in COSMOS, had no significant effect on any of the five epigenetic clocks tested.

The authors are measured about what remains to be established — whether epigenetic clock improvements translate to hard clinical endpoints requires longer follow-up and larger studies. But the precision nutrition implication is clear: the patients most likely to benefit from micronutrient supplementation are those already showing biological age acceleration, not those who are nutritionally replete.

Read the full paper here: https://doi.org/10.1038/s41591-026-04239-3

05/18/2026

What if a single AI model — trained only to predict the next measurement in a patient's physiological record — could forecast disease risk, track individual responses to nutrition interventions, and simulate the expected effects of statins, antihypertensives, and GLP-1 agonists, all without being explicitly programmed to do any of these things?

That is precisely what Lutsker et al. demonstrate with HealthFormer, a decoder-only transformer trained on data from the Human Phenotype Project, a longitudinal cohort of over 15,000 deeply phenotyped individuals.

The model tokenizes each participant's health trajectory across 667 measurements spanning blood biomarkers, body composition, sleep physiology, continuous glucose monitoring, gut microbiome, wearable-derived physiology, and behavioral and medication data. From a single self-supervised training objective — predict the next token — the full range of clinical downstream tasks emerges as queries on the same model.

The performance benchmarks across four independent cohorts are significant. Without fine-tuning, HealthFormer improved prediction for 27 of 30 incident disease and mortality endpoints over a standard age-sex-BMI baseline, and outperformed established clinical risk scores — including Framingham CVD and PREVENT-ASCVD — in every direct comparison. Concordance indices reached 0.834 for chronic kidney disease and 0.826 for cardiovascular mortality.

The intervention simulation results are what elevate this paper beyond standard clinical AI benchmarking. In the fully held-out PNP3 personalised nutrition trial, the model predicted individual six-month biomarker responses with correlations of r=0.78 for diastolic blood pressure and r=0.89 for triglycerides — zero-shot. Across 41 randomised trial comparisons covering lipid-lowering agents, antihypertensives, glucose-lowering drugs, exercise modalities, and dietary interventions, predicted direction of effect matched published trial estimates in every case.

The predicted mean fell within the published 95% confidence interval in 30 of 41 comparisons, without any task-specific training.
The authors are precise about what this does and does not represent. HealthFormer generates prognostic stratification under observed intervention exposures — it is not a causal counterfactual engine.

Its under-predictions at the high-potency end of the drug-effect distribution are coherent and mechanistically interpretable. But the directional fidelity across 41 independent trial comparisons, spanning diverse drug classes and physiological systems, marks a meaningful threshold in what generative physiological modelling can achieve.

For those working at the frontier of precision and functional medicine, this paper deserves careful reading. It describes not a finished clinical tool, but the generative substrate from which clinical digital twins may ultimately be built.

Read the full preprint here: https://arxiv.org/abs/2604.27899

05/12/2026

A new study published in Cell Genomics (Liu et al., June 2026) does something most aging research cannot: it moves beyond correlation to establish causality between chronic inflammation and biological age acceleration.

The investigators analyzed four independent human cohorts ranging from young, healthy adults (mean age 25) to elderly individuals with established multimorbidity (mean age 69–72), measuring circulating inflammatory proteins alongside DNA methylation-based epigenetic aging scores. Four epigenetic clocks were assessed — Horvath and Hannum, which predict lifespan, and GrimAge and PhenoAge, which predict health span. The health-span clocks showed markedly stronger and more consistent associations with inflammatory proteins, frailty, and the cumulative burden of age-related diseases including COPD and malignancies. Chronological age, by contrast, was associated only with hypertension. This finding reinforces that biological age, particularly as captured by GrimAge and PhenoAge, is the more clinically meaningful variable.

The central contribution of this paper is its Mendelian randomization analysis. Drawing on protein quantitative trait loci from the UK Biobank (over 33,000 participants) and epigenetic age acceleration GWAS data from a non-overlapping cohort of nearly 35,000, the authors established that four circulating proteins — CXCL9, CXCL10, CCL11, and IL-18 — are causal drivers of epigenetic age acceleration. CXCL9 produced the strongest causal signal, surviving multiple-testing correction and replicating across five independent MR methods. Reverse MR revealed minimal evidence that epigenetic aging causes the inflammatory changes, supporting a directionality in which inflammation precedes and accelerates biological aging.

All four of these proteins are mechanistically connected to the interferon signaling pathway, a finding the authors corroborate through transcription factor enrichment analysis showing that IRF1, STAT1, and STAT3 are the dominant upstream regulators of the EAA-associated protein network. The study also documents that aging is associated with reduced IFN-γ production by lymphocytes in response to microbial stimulation — a finding consistent with immunosenescence, and one that points to a dual pathology: chronic low-grade interferon activation coexisting with impaired adaptive immune responsiveness.

The clinical implication is direct. The interferon pathway is not a passive bystander in biological aging — it is a causal mechanism and a plausible therapeutic target. For practitioners working at the intersection of longevity, functional medicine, and immunology, this paper offers both a mechanistic framework and a rationale for future intervention studies using interferon-modulating agents.

Read the full paper here:

https://doi.org/10.1016/j.xgen.2026.101218

05/07/2026

Why does the same vaccine produce a strong immune response in one person and a weak one in another? Why do some patients respond to cancer immunotherapy while others don't — even when their tumors look similar? A landmark paper published in Cell (Babdor et al., 2026) suggests that part of the answer is written in the gut.

The ImmunoMicrobiome study profiled 110 healthy adults using a comprehensive multi-omic approach — single-cell mass cytometry, transcriptomics, plasma proteomics, shotgun metagenomics, and stool metabolomics — to map how the immune system and gut microbiome vary across individuals at steady state.

Using multi-omic factor analysis, the researchers identified two major axes of immune variation in healthy people. The most clinically significant captured coordinated co-variation between specific immune cell states, microbiome pathway abundances, and stool metabolites simultaneously. This microbiome-associated axis was enriched for tonic interferon signaling — the low-level, constitutive interferon activity that calibrates antiviral immunity across all immune cell types. Individuals with high scores showed expanded SIGLEC-1high monocytes with enhanced antigen presentation capacity, activated memory T cells, and elevated circulating IFN-γ and interferon-stimulated chemokines in plasma.

The microbial features linked to this immune state included short-chain fatty acid biosynthesis, polyamine metabolism, and primary bile acid production — with Bifidobacterium species among the key contributors. Critically, microbial functional pathways and metabolites were more strongly linked to immune variation than the abundances of individual species. What the microbiome does matters more than which bacteria are present.

These immune and microbiome signatures were remarkably stable within individuals over approximately 20 months of follow-up. And when applied to external datasets, the tonic interferon signature predicted stronger influenza vaccine responses and identified cancer patients who required JAK inhibition alongside checkpoint blockade to respond to immunotherapy.

This paper establishes the microbiome not as a generic health variable, but as a calibrator of individual immune setpoints with measurable consequences for infection susceptibility and therapeutic response. Read the full paper.

DOI: https://doi.org/10.1016/j.cell.2026.02.003

05/06/2026

We have been thinking about obesity wrong — and a major review in Nature Reviews Endocrinology makes that case with compelling mechanistic force.

The lymphatic vasculature has long been treated as a passive transport system, largely irrelevant to metabolic disease. De Nardo and colleagues at Monash University and the Baker Heart and Diabetes Institute systematically dismantle that assumption. What emerges is a picture of the lymphatic system as a central, bidirectional driver of adipose tissue dysfunction, insulin resistance, and the comorbidities that define obesity at the tissue level.

The relationship operates in both directions. Obesity remodels white adipose tissue to produce a pro-inflammatory secretome — elevated VEGFC, TNF, leptin, free fatty acids, and prostaglandin E2 — that impairs lymphatic endothelial cell integrity, drives disordered vessel growth, suppresses contractile activity in lymphatic muscle cells, and increases vessel permeability. The result is lymphatic vessels that leak their contents — chylomicrons, ceramides, cytokines — directly into the surrounding visceral fat.

That leaked lymph then drives further adipocyte expansion, local insulin resistance, and systemic metabolic dysfunction, amplifying the very conditions that caused the lymphatic failure in the first place. Adipose tissue immediately adjacent to leaky mesenteric lymphatics shows measurably impaired insulin-stimulated glucose uptake — a direct spatial link between lymphatic integrity and metabolic function documented in the paper.

Critically, the evidence shows that lymphatic dysfunction can also initiate obesity, not merely result from it. Genetic models with defective mesenteric lymphatics develop spontaneous adult-onset obesity, reversed by restoring lymphatic integrity.

Pharmacologically slowing lymph transport in otherwise healthy rats produces adiposity and hyperglycaemia. The causal arrow runs in both directions, and the cycle is self-sustaining.

The review also reframes how GLP1 receptor agonists may work. GLP1 is present in mesenteric lymph at concentrations up to 80-fold higher than in plasma. The GLP1 receptor is expressed on collecting lymphatic vessels, and semaglutide has been shown to directly restore lymphatic contractile function in preclinical models. Case reports document meaningful reductions in lymphoedema severity in humans, and a clinical trial is now underway.

For clinicians working in metabolic medicine, this paper repositions the lymphatic system as a mechanistically central and therapeutically accessible target in obesity — one that the field has largely overlooked until now. Read the full paper to understand why that is about to change.

https://doi.org/10.1038/s41574-026-01243-y

05/05/2026

Most of us assume aging happens uniformly — that the body ages as a whole, at a single pace. A major study published in The Lancet Digital Health this year demonstrates that assumption is wrong, and the implications for how we understand, predict, and ultimately prevent age-related disease are profound.
Researchers from University College London, the University of Helsinki, and Stanford University analyzed plasma proteomic data from 6,235 middle-aged adults enrolled in the Whitehall II cohort study. Using a validated, aptamer-based proteomics platform and organ-specific protein signatures, they calculated biological age gaps — the degree to which each of nine organ systems was aging faster or slower than expected for a given chronological age — and then tracked participants for a mean of nearly 20 years through national health records, monitoring the development of 45 age-related diseases.

What the data revealed is that organ aging is neither strictly localized nor uniformly systemic. Of the 30 diseases significantly associated with accelerated organ aging, only six showed strict organ specificity — meaning the disease was exclusively linked to aging in its own organ. These included chronic heart failure, dilated cardiomyopathy, and liver failure.

For the remaining 24 diseases, risk was distributed across multiple organ age gaps, often crossing anatomical boundaries in ways that are clinically counterintuitive. Dementia's strongest predictor was accelerated immune system aging. Parkinson's disease was most strongly linked to intestinal aging. End-stage renal disease was associated with heart, brain, liver, and immune system age gaps — but not the kidney age gap itself.

More strikingly, accelerated aging in nearly every organ was associated with substantially elevated risk of multiorgan multimorbidity — the development of two or three co-occurring diseases across different organ systems within the same individual. The hazard ratios for this outcome, adjusted for all other organ age gaps simultaneously, ranged up to 2.03 for arterial age gap and 1.78 for kidney age gap. This is the biological architecture underlying the clinical complexity of aging patients, and it was detectable from a single blood draw taken in midlife — up to two decades before disease onset.

The authors are careful to note that this remains observational science, and that clinical application of plasma-based organ age profiling will require further validation across more diverse populations. But the direction of travel is clear: a non-invasive, scalable tool that maps nine organ biological ages from one blood sample, predicts decades of disease risk, and identifies which organs are aging fastest — is not a distant proposition. It is an emerging clinical reality.

For those of us in precision and functional medicine, this paper reframes the longevity assessment entirely. Read the full paper to understand how.

DOI: https://doi.org/10.1016/j.landig.2025.01.004

Anil Bajnath, MD

06/01/2026

05/26/2026

05/21/2026

05/20/2026

05/19/2026

05/18/2026

05/12/2026

05/07/2026

05/06/2026

05/05/2026

Address

Opening Hours

Website

Alerts

Contact The Practice

Shortcuts

Share

Category

Monday	9am - 5pm
Wednesday	9am - 5pm
Friday	9am - 5pm
Saturday	9am - 5pm