The Silent Culprit That Might Be Steering Us Towards Metabolic Disorders
Korean scientists have revealed a unique signaling route linked to age-associated chronic metabolic issues.
Led by Professor Jong Kyoung Kim of POSTECH’s Department of Life Sciences, in collaboration with Professor Seung-Hoi Koo from the Division of Life Sciences at Korea University and main researcher Geum-Sook Hwang of the Korea Basic Science Institute (KBSI), the team identified an age-related impairment in the BCAA metabolic process.
This impairment causes adipose cell malfunctions and chronic metabolic problems.
Their results were published in Nature Aging.
Adipose cells are pivotal in overseeing energy metabolism. These cells, alongside preadipocyte cells and various immune cells in adipose tissue, experience cellular aging.
Secretions from these aging cells speed up the aging process and weaken adipose tissue functions. As a result, fats build up in the liver and muscles, setting off metabolic issues and shortening healthy life duration.
Previously, in a study in Nature Communications, Professor Seung-Hoi Koo’s team discovered that excessive CRTC2 activity results in insulin resistance, fatty liver, and weight gain. But the influence of CRTC2 on aging and its related problems in adipocytes had not been studied.
This new investigation establishes that an aging-driven upsurge in adipose CRTC2 speeds up cellular aging, causing dysfunction in adipocytes and age-linked metabolic problems. CRTC2 reduces PPAR gamma in adipocytes and hampers BCAA breakdown.
The resulting effect is the activation of mTORC1, as shown in the integrated metabolome-transcriptome analysis. The boosted mTORC1 activity initiates cellular aging and affects mitochondrial balance, hastening the aging process.
When assessing single-cell genetic data, older mice showed more SASP, especially IL-1beta and TNF-alpha. This reshapes adipose tissue by limiting the differentiation capability of preadipocyte cells and immune cell regulations.
Intriguingly, mice without CRTC2 in their adipose cells had restrained BCAA-mTORC1 activation, limiting age-related metabolic disorders. This implies the potential to slow aging by managing CRTC2 or BCAA breakdown.
Highlighting the study’s importance, Professor Seung-Hoi Koo added that their work used advanced omics technologies to expose how aging-driven CRTC2 rise in adipocytes results in BCAA breakdown dysfunction, leading to cellular aging and metabolic issues.
“Consequently, selective inhibition of CRTC2 or activation of PPAR gamma in adipocytes may hold the potential to inhibit aging and extend health span.”
This research was facilitated by grants from the Korea Mouse Phenotyping Center Project, the Mid-Career Researcher Project of the National Research Foundation of Korea under the Ministry of Science and ICT, and other national science and technology projects.
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