The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan

Yen, Kelvin; Mehta, Hemal H.; Kim, Su-Jeong; Lue, Yanhe; Hoang, James; Guerrero, Noel; Port, Jenna; Bi, Qiuli; Navarrete, Gerardo; Brandhorst, Sebastian; Lewis, Kaitlyn N.; Wan, Junxiang; Swerdloff, Ronald S.; Mattison, Julie A.; Buffenstein, Rochelle; Breton, Carrie V.; Wang, Christina; Longo, Valter D.; Atzmon, Gil; Wallace, Douglas C.; Barzilai, Nir; Cohen, Pinchas

doi:10.18632/aging.103534

Cited by 81 publications

(67 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The progression of pathology is also conditioned by insidious aspect of mitochondrial signaling under oxidative stress, such as the persistent activation of UPR mt , which may exacerbate the disruption of neurons in vivo or induce the release of neuroprotective mitokines in AD, such as humanin [ 202 , 203 ]. Humanin reduce the neuroinflammation and the oxidative stress-induced injury in AD, diminishing the level of protein aggregation and of plaque deposition [ 204 , 205 ].…”

Section: Mitochondrial Oxidative Stress and Mito-inflammation In Imentioning

confidence: 99%

Mitochondrial Oxidative Stress and “Mito-Inflammation”: Actors in the Diseases

et al. 2021

View full text Add to dashboard Cite

A decline in mitochondrial redox homeostasis has been associated with the development of a wide range of inflammatory-related diseases. Continue discoveries demonstrate that mitochondria are pivotal elements to trigger inflammation and stimulate innate immune signaling cascades to intensify the inflammatory response at front of different stimuli. Here, we review the evidence that an exacerbation in the levels of mitochondrial-derived reactive oxygen species (ROS) contribute to mito-inflammation, a new concept that identifies the compartmentalization of the inflammatory process, in which the mitochondrion acts as central regulator, checkpoint, and arbitrator. In particular, we discuss how ROS contribute to specific aspects of mito-inflammation in different inflammatory-related diseases, such as neurodegenerative disorders, cancer, pulmonary diseases, diabetes, and cardiovascular diseases. Taken together, these observations indicate that mitochondrial ROS influence and regulate a number of key aspects of mito-inflammation and that strategies directed to reduce or neutralize mitochondrial ROS levels might have broad beneficial effects on inflammatory-related diseases.

show abstract

Section: Mitochondrial Oxidative Stress and Mito-inflammation In Imentioning

confidence: 99%

Mitochondrial Oxidative Stress and “Mito-Inflammation”: Actors in the Diseases

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Mitochondrial-derived peptides (MDPs) are biologically active peptides derived from small open reading frames (ORF) in the mitochondrial genome [ 12 – 16 ]. Emerging studies suggest that mtDNA polymorphisms could impact mitochondrial-derived peptides levels.…”

Section: Introductionmentioning

confidence: 99%

A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c

Zempo

Kim

Fuku

et al. 2021

Aging

Self Cite

View full text Add to dashboard Cite

Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro . Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.

show abstract

“…Consistently with the idea that HN has not only cytoprotective but also anti-inflammatory roles, it has been found that HN has protective roles not only in AD [ 94 ] but also in T2D, CVD and atherosclerosis [ 95 , 99 – 101 ], which are all considered inflammaging-related diseases [ 102 , 103 ]. Moreover, very recently it has been reported that HN, and probably other mitochondria-derived peptides, improves not only health status but also lifespan [ 104 ]. In particular, Yen and co-workers found that the overexpression of HN increases lifespan in C. elegans , while middle-aged mice treated with the potent humanin analogue HNG showed an improvement in health parameters [ 104 ].…”

Section: Mitokines In Immune Responsesmentioning

confidence: 99%

“…Moreover, very recently it has been reported that HN, and probably other mitochondria-derived peptides, improves not only health status but also lifespan [ 104 ]. In particular, Yen and co-workers found that the overexpression of HN increases lifespan in C. elegans , while middle-aged mice treated with the potent humanin analogue HNG showed an improvement in health parameters [ 104 ]. Literature data are still controversial as far as the age-related changes in HN circulating levels.…”

Section: Mitokines In Immune Responsesmentioning

confidence: 99%

Mitochondria, immunosenescence and inflammaging: a role for mitokines?

et al. 2020

View full text Add to dashboard Cite

A global reshaping of the immune responses occurs with ageing, indicated as immunosenescence, where mitochondria and mitochondrial metabolism play an important role. However, much less is known about the role of mitochondrial stress response in this reshaping and in particular of the molecules induced by such response, collectively indicated as mitokines. In this review, we summarize the current knowledge on the role of mitokines in modulating immune response and inflammation focusing on GDF15, FGF21 and humanin and their possible involvement in the chronic age-related low-grade inflammation dubbed inflammaging. Although many aspects of their biology are still controversial, available data suggest that these mitokines have an anti-inflammatory role and increase with age. Therefore, we hypothesize that they can be considered part of an adaptive and integrated immune-metabolic mechanism activated by mitochondrial dysfunction that acts within the framework of a larger anti-inflammatory network aimed at controlling both acute inflammation and inflammaging.

show abstract

The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan

Cited by 81 publications

References 81 publications

Mitochondrial Oxidative Stress and “Mito-Inflammation”: Actors in the Diseases

Mitochondrial Oxidative Stress and “Mito-Inflammation”: Actors in the Diseases

A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c

Mitochondria, immunosenescence and inflammaging: a role for mitokines?

Contact Info

Product

Resources

About