Discovery of aging mechanism for hematopoietic stem cells

December 24, 2020

By transferring mouse aged hematopoietic stem cells (aged HSCs, *1) to the environment of young mice (bone marrow niche, *2), it was demonstrated that the pattern of stem cell gene expression was rejuvenated to that of young hematopoietic stem cells. On the other hand, the function of aged HSCs did not recover in the young bone marrow niche. The epigenome (DNA methylation, *3) of aged HSCs did not change significantly even in the young bone marrow niche, and DNA methylation profiles were found to be a better index than the gene expression pattern of aged HSCs.

A research group led by Professor Atsushi Iwama at the Division of Stem Cell and Molecular Medicine, The Institute of Medical Science, The University of Tokyo (IMSUT) announced these world-first results and was published in the Journal of Experimental Medicine (online) on November 24th.

"The results will contribute to the development of treatments for age-related blood diseases," states lead scientist, Professor Iwama at IMSUT.

Focus on changes in aged HSCs in the bone marrow niche

The research group investigated whether rejuvenating aged HSCs in a young bone marrow niche environment would rejuvenate.

Tens of thousands of aged hematopoietic stem/progenitor cells collected from 20-month-old mice were transplanted into 8-week-old young mice without pretreatment such as irradiation. After two months of follow-up, they collected bone marrow cells and performed flow cytometric analysis.

The research team also transplanted 10-week-old young mouse HSCs for comparison. In addition, engrafted aged HSCs were fractionated and RNA sequence analysis and DNA methylation analysis were performed.

They found that engrafted aged HSCs were less capable of producing hematopoietic cells than younger HSCs. They also showed that differentiation of aged HSCs into multipotent progenitor cells was persistently impaired even in the young bone marrow niche, and that the direction of differentiation was biased. It was found that the transfer of aged HSCs to the young bone marrow niche does not improve their stem cell function.

See the paper for details.

A more detailed analysis may reveal mechanisms that irreversibly affect aged HSC function

Aging studies focusing on HSCs have been actively pursued in mice using a bone marrow transfer model. However, the effect of aging on HSCs remains to be clarified.

Professor Iwama states as follows."This study has a significant impact because it clarified the effect of aging on HSCs. Our results are expected to contribute to further elucidation of the mechanism of aging in HSCs and understanding of the pathogenic mechanism of age-related blood diseases."
-end-
Research Notes

(*1) Aged hematopoietic stem cells (aged HSCs)

The functions and characteristics of hematopoietic stem cells change with age. The ability to produce blood cells is reduced and differentiation is biased, increasing the risk of developing myeloid tumors.

(*2) Bone marrow niche

The microenvironment in the bone marrow that is essential for maintaining hematopoietic stem cells.

(*3) Epigenome (DNA methylation)

Chemical modification of genomic DNA and histone proteins. The epigenome is acquired and changes according to cell conditions. DNA methylation acts to suppress gene expression (transcription).

The Institute of Medical Science, The University of Tokyo

Related Aging Articles from Brightsurf:

Surprises in 'active' aging
Aging is a process that affects not only living beings.

Aging-US: 'From Causes of Aging to Death from COVID-19' by Mikhail V. Blagosklonny
Aging-US recently published ''From Causes of Aging to Death from COVID-19'' by Blagosklonny et al. which reported that COVID-19 is not deadly early in life, but mortality increases exponentially with age - which is the strongest predictor of mortality.

Understanding the effect of aging on the genome
EPFL scientists have measured the molecular footprint that aging leaves on various mouse and human tissues.

Muscle aging: Stronger for longer
With life expectancy increasing, age-related diseases are also on the rise, including sarcopenia, the loss of muscle mass due to aging.

Aging memories may not be 'worse, 'just 'different'
A study from the Department of Psychological & Brain Sciences in Arts & Sciences adds nuance to the idea that an aging memory is a poor one and finds a potential correlation between the way people process the boundaries of events and episodic memory.

A new biomarker for the aging brain
Researchers at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan have identified changes in the aging brain related to blood circulation.

Scientists invented an aging vaccine
A new way to prevent autoimmune diseases associated with aging like atherosclerosis, Alzheimer's disease, and Parkinson's disease was described in the article.

The first roadmap for ovarian aging
Infertility likely stems from age-related decline of the ovaries, but the molecular mechanisms that lead to this decline have been unclear.

Researchers discover new cause of cell aging
New research from the USC Viterbi School of Engineering could be key to our understanding of how the aging process works.

Deep Aging Clocks: The emergence of AI-based biomarkers of aging and longevity
The advent of deep biomarkers of aging, longevity and mortality presents a range of non-obvious applications.

Read More: Aging News and Aging Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.