Protein Key to Lifespan and Healthy Aging Identified

Summary: A new study reveals the significant role of the CD300f immune receptor in determining life expectancy and healthy aging in mice. The absence of this protein in immune system cells, particularly in macrophages and microglia, leads to shorter life spans and pathologies related to cognitive decline and premature aging, with a more pronounced effect in females.

This discovery is crucial for understanding the aging process and could inform strategies for targeting CD300f in biomedicine, potentially serving as a biomarker in patients. The research also aims to explore the role of this immune receptor in brain aging and its potential link to Alzheimer’s disease.

Key Facts:

  1. Mice lacking the CD300f immune receptor exhibit premature aging symptoms and cognitive pathologies.
  2. The study’s long-term animal monitoring offers a realistic view of aging processes without accelerated aging models.
  3. The research may lead to new insights into the relationship between immune system dysfunction, aging, and Alzheimer’s disease.

Source: University of Barcelona

Life expectancy and healthy aging in mice can be determined by a protein present in some cells of the immune system, according to a study published in the journal Cell Reports.

When this protein — known as the CD300f immune receptor — is absent, animal models have a shorter life expectancy and suffer from pathologies associated with cognitive decline and premature aging, especially in females.

This shows an older man.
The researcher points out that “the aim is to keep studying the consequences of the dysfunction of the CD300f immune receptor on brain ageing, in particular on microglia”. Credit: Neuroscience News

“Our study indicates that alterations in immune system cells, for instance, in macrophages and microglia, can determine the healthy aging degree in mice”, notes Hugo Peluffo, leader of this study and member of the Faculty of Medicine and Health Sciences and the Institute of Neurosciences (UBneuro) of the University of Barcelona.

Understanding how the CD300f immune receptor — and the myeloid cells of the immune system — can determine by themselves the onset rate of ageing-associated pathologies, “will help to better understand this process, and it will contribute to the design of strategies to regulate its action. For instance, using the immune receptor CD300f as a target in biomedicine”, notes the expert. “Also, our team has previously shown that some variants of the CD300f immune receptor could be useful as biomarkers in patients”.

The paper, whose first author is the expert Frances Evans (Institute Pasteur and Udelar), includes the participation of teams from the Molecular Imaging Uruguayan Center (CUDIM), among other institutions.

What is the role of this receptor in aging?

The CD300f receptor is a protein expressed by immune system cells that modulates cell metabolism and inflammation. This study reveals the first evidence of its role in the processes related to aging and senescence.

“In particular, we discovered that mice that lacked the CD300f immune receptor developed prematurely some pathologies associated with aging (cognitive deficits, motor incoordination, tumours, etc.) and even damage in several organs such as the brain, the liver or the lungs. Moreover, we observed an important effect on females, the most affected ones”, says Hugo Peluffo.

The study is based on a detailed monitoring of several cohorts of animals for thirty months, a methodological innovation that allowed the researchers to see the process of real aging in these animals without using accelerated aging models, which do not fully represent a process that necessarily involves the gradual accumulation of changes with age.

Immune receptors and Alzheimer’s disease

The researcher points out that “the aim is to keep studying the consequences of the dysfunction of the CD300f immune receptor on brain aging, in particular on microglia”.

In these lines, a project led by Professor Hugo Peluffo to study the relationship between aging and Alzheimer’s disease has just received one of the Alzheimer’s research grants from the Pasqual Maragall Foundation. It will explore how immune cells in the nervous system, known as microglia, influence the aging process and the late onset of Alzheimer’s.

“In this project, funded by the Pasqual Maragall Foundation, we will study the potential role of this immune receptor in Alzheimer’s disease”, says the researcher.

About this aging and longevity research news

Author: Rosa Martínez
Source: University of Barcelona
Contact: Rosa Martínez – University of Barcelona
Image: The image is credited to Neuroscience News

Original Research: Open access.
CD300f immune receptor contributes to healthy ageing by regulating inflammaging, metabolism, and cognitive decline” by Hugo Peluffo et al. Cell Reports


CD300f immune receptor contributes to healthy ageing by regulating inflammaging, metabolism, and cognitive decline


  • CD300f−/− mice show reduced lifespan, but no specific cause of death is identified
  • This is associated with inflammaging, senescence, frailty, and cognitive decline
  • CD300f−/− mice exhibit microglial aging states and sex-dependent metabolic changes
  • Absence of CD300f reduces macrophage immunometabolic fitness in a sex-dependent way


Emerging evidence suggests that immune receptors may participate in many aging-related processes such as energy metabolism, inflammation, and cognitive decline. CD300f, a TREM2-like lipid-sensing immune receptor, is an exceptional receptor as it integrates activating and inhibitory cell-signaling pathways that modulate inflammation, efferocytosis, and microglial metabolic fitness.

We hypothesize that CD300f can regulate systemic aging-related processes and ultimately healthy lifespan. We closely followed several cohorts of two strains of CD300f−/− and WT mice of both sexes for 30 months and observed an important reduction in lifespan and healthspan in knockout mice.

This was associated with systemic inflammaging, increased cognitive decline, reduced brain glucose uptake observed by 18FDG PET scans, enrichment in microglial aging/neurodegeneration phenotypes, proteostasis alterations, senescence, increased frailty, and sex-dependent systemic metabolic changes. Moreover, the absence of CD300f altered macrophage immunometabolic phenotype.

Taken together, we provide strong evidence suggesting that myeloid cell CD300f immune receptor contributes to healthy aging.

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