GDF15 protects from age‐related metabolic phenotypes

A recent study shows an important role for GDF15 in preventing aging-induced metabolic phenotypes by modulating systemic inflammatory responses in humans and mice.

Dysfunction of mitochondria—commonly called the “energy-producing engine of the cells”—has been implicated in various human diseases, which reflects their importance in physiological cellular and organismal function.

Longevity.Technology: recently, mitochondrial dysfunction has emerged as a hallmark of aging and aging-mediated inflammatory responses, suggesting that reversing mitochondrial dysfunction may represent a promising strategy to treat age-related disorders, including insulin resistance and type 2 diabetes [1,2].

A research team at the Chungnam National University Hospital of the Chungnam National University School of Medicine, Republic of Korea, was led to the exciting discovery that growth differentiation factor 15 (GDF15) attenuates aging-mediated systemic inflammatory responses, preventing metabolic deterioration and insulin resistance in humans and mice. The study was led by Ji Sun Moon and overseen by Dr Hyon-Seung Yi, and the manuscript was published on July 21, 2020, in the journal Aging Cell [3].

GDF15 is a protein released by mitochondria in response to mitochondrial stress and dysfunction [4]. Although its serum levels are known to increase in metabolic stress-mediated inflammation, its role in aging has remained largely unclear.


 

The findings of this study strongly support that GDF15 production in response to mitochondrial stress is a homeostatic mechanism protecting from aging‐induced systemic inflammation.

 


 

The study by Ji Sun Moon et al. shows that elderly individuals have elevated levels of GDF15 in the serum and liver and that the levels are associated with aging‐induced inflammation. Additionally, they show that high GDF15 levels are linked to increased mitochondrial DNA levels in the plasma—a marker of mitochondrial stress.

Additionally, the study shows that increased body weight and systemic inflammation are more frequent among individuals with low GDF15 levels in the blood.

Consistent with their findings in humans, the researchers found that mice with high hepatic Gdf15 expression often exhibit metabolic dysfunction and die earlier.

Importantly, the researchers genetically depleted GDF15 and found that GDF15-deficient aging mice exhibited enhanced liver inflammation, damage, and fat deposition.

The findings of this study strongly support that GDF15 production in response to mitochondrial stress is a homeostatic mechanism protecting from aging‐induced systemic inflammation and metabolic syndromes in humans and mice. Future studies are required to improve our understanding of the mechanisms underlying the protective effects of GDF15 on aging, as well as investigate its potential use in novel therapeutic approaches to treat age-related conditions and promote Longevity in humans.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627182/

[2] https://www.hindawi.com/journals/jst/2012/646354/

[3] https://onlinelibrary.wiley.com/doi/10.1111/acel.13195

[4] https://pubmed.ncbi.nlm.nih.gov/27018280/

Carla Heyworth
Carla is sub editor at Longevity.Technology and she's the glue that keeps the team on track and the articles rolling-out. She has an extensive background in B2B communications, events and marketing. Carla's a visual person and can often be found behind a camera or editing photos

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