Evidence map›Paper›PMID 38244754›Full record

ArticleBrain research2024

Altered metabolism and DAM-signatures in female brains and microglia with aging.

Nicholas R W Cleland, Garrett J Potter, Courtney Buck, Daphne Quang, Dean Oldham, Mikaela Neal, Anthony Saviola, Christy S Niemeyer, Evgenia Dobrinskikh, Kimberley D Bruce

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Inflammaging and the sex-frailty paradox.Aging clinical and experimental research · 2025
    Article
  9. Review
  10. Article
  11. Review
  12. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Nicholas R W ClelandDivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Garrett J PotterDivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Courtney BuckDivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Daphne QuangDivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Dean OldhamDivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Mikaela NealDivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Anthony SaviolaDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Christy S NiemeyerDepartment of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Evgenia DobrinskikhSection of Neonatology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, USA.
Kimberley D BruceDivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: kimberley.bruce@cuanschutz.edu.
University of Colorado Anschutz Medical Campus · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
ZEBRAFISH TRANSGENIC CORE - ROCKY MOUNTAIN NEUROLOGICAL DISORDERS CORE CENTERP30NS048154 · NINDS · UNIVERSITY OF COLORADO DENVER · PI RIBERA, ANGELES BADELL · 2004 to 2020
$10.1M
Targeting Microglial Lipoprotein Lipase in Alzheimer's diseaseR01AG079217 · NIA · UNIVERSITY OF COLORADO DENVER · PI Kimberley D Bruce · 2022 to 2026
$3.0M
Developing Fluorescence Lifetime Imaging Microscopy (FLIM) as a novel method to measure microglial metabolism in situR03NS118230 · NINDS · UNIVERSITY OF COLORADO DENVER · PI BRUCE, KIMBERLEY D · 2020 to 2020
$156k
NCI NIH HHS P30 CA046934NIA NIH HHS R01 AG079217NINDS NIH HHS P30 NS048154NINDS NIH HHS R03 NS118230
6 · The paper itself

Abstract

Despite Alzheimer's disease (AD) disproportionately affecting women, the mechanisms remain elusive. In AD, microglia undergo 'metabolic reprogramming', which contributes to microglial dysfunction and AD pathology. However, how sex and age contribute to metabolic reprogramming in microglia is understudied. Here, we use metabolic imaging, transcriptomics, and metabolic assays to probe age- and sex-associated changes in brain and microglial metabolism. Glycolytic and oxidative metabolism in the whole brain was determined using Fluorescence Lifetime Imaging Microscopy (FLIM). Young female brains appeared less glycolytic than male brains, but with aging, the female brain became 'male-like.' Transcriptomic analysis revealed increased expression of disease-associated microglia (DAM) genes (e.g., ApoE, Trem2, LPL), and genes involved in glycolysis and oxidative metabolism in microglia from aged females compared to males. To determine whether estrogen can alter the expression of these genes, BV-2 microglia-like cell lines, which abundantly express DAM genes, were supplemented with 17β-estradiol (E2). E2 supplementation resulted in reduced expression of DAM genes, reduced lipid and cholesterol transport, and substrate-dependent changes in glycolysis and oxidative metabolism. Consistent with the notion that E2 may suppress DAM-associated factors, LPL activity was elevated in the brains of aged female mice. Similarly, DAM gene and protein expression was higher in monocyte-derived microglia-like (MDMi) cells derived from middle-aged females compared to age-matched males and was responsive to E2 supplementation. FLIM analysis of MDMi from young and middle-aged females revealed reduced oxidative metabolism and FAD+ with age. Overall, our findings show that altered metabolism defines age-associated changes in female microglia and suggest that estrogen may inhibit the expression and activity of DAM-associated factors, which may contribute to increased AD risk, especially in post-menopausal women.

Indexed as

Alzheimer DiseaseMicrogliaAgedAgingAnimalsBrainEstrogensFemaleHumansMaleMembrane GlycoproteinsMiceMiddle AgedReceptors, ImmunologicEstrogensMembrane GlycoproteinsReceptors, ImmunologicTrem2 protein, mouseAgingAlzheimer’s diseaseLipidsLipoprotein lipaseMetabolismMicrogliaSex differences

Identifiers

PMID38244754
PMCPMC12036313
OpenAlexW4390969423

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.