Humanin and Age-Related Diseases: A New Link?

Gong, Zhaohui; Tas, Emir; Muzumdar, Radhika

doi:10.3389/fendo.2014.00210

Cited by 93 publications

(100 citation statements)

References 106 publications

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“…We found significant upregulation of genes involved in glycolytic pathways in cardiomyocytes subjected to hypoxia demonstrating a shift in energy production from mitochondria to glycolysis (Jian et al , 2011b). Recently it has been found that humanin, a mitochondria derived peptide, exhibits strong cytoprotective actions against various stress and disease models and suggested to be part of a retrograde signaling that involves nuclear-mitochondria crosstalk (Gong et al , 2014). This inter-organelle communication is important in the mitochondrial response to hypoxic-ischemic conditions, whether induced by stroke, myocardial-infarction or sepsis.…”

Section: Hypoxic-ischemic Injurymentioning

confidence: 99%

Mitochondrial function in hypoxic ischemic injury and influence of aging

Ham

Raju

2017

Progress in Neurobiology

282

205

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Mitochondria are a major target in hypoxic/ischemic injury. Mitochondrial impairment increases with age leading to dysregulation of molecular pathways linked to mitochondria. The perturbation of mitochondrial homeostasis and cellular energetics worsens outcome following hypoxic-ischemic insults in elderly individuals. In response to acute injury conditions, cellular machinery relies on rapid adaptations by modulating posttranslational modifications. Therefore, post-translational regulation of molecular mediators such as hypoxia-inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), c-MYC, SIRT1 and AMPK play a critical role in the control of the glycolytic-mitochondrial energy axis in response to hypoxic-ischemic conditions. The deficiency of oxygen and nutrients leads to decreased energetic reliance on mitochondria, promoting glycolysis. The combination of pseudohypoxia, declining autophagy, and dysregulation of stress responses with aging adds to impaired host response to hypoxic-ischemic injury. Furthermore, intermitochondrial signal propagation and tissue wide oscillations in mitochondrial metabolism in response to oxidative stress are emerging as vital to cellular energetics. Recently reported intercellular transport of mitochondria through tunneling nanotubes also play a role in the response to and treatments for ischemic injury. In this review we attempt to provide an overview of some of the molecular mechanisms and potential therapies involved in the alteration of cellular energetics with aging and injury with a neurobiological perspective.

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Section: Hypoxic-ischemic Injurymentioning

confidence: 99%

Mitochondrial function in hypoxic ischemic injury and influence of aging

Ham

Raju

2017

Progress in Neurobiology

282

205

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“…The extracellular actions of humanin are largely mediated through its cell membrane receptors (16 -17). Humanin has potent neuroprotective (18), antiapoptotic (19), and IGFBP3-binding (20) cytoprotective effects with broad-spectrum actions on the brain, pancreas, heart, and testis (21)(22). Eriksson and colleagues (23) recently showed that cotreatment of a potent humanin analog HNG with a proteasome inhibitor bortezomib was effective in preventing bortezomib-induced bone growth impairment without interfering with bortezomib's anticancer effects in immune deficient nude mice.…”

mentioning

confidence: 99%

The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice

et al. 2015

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Humanin is a peptide that is cytoprotective against stresses in many cell types. We investigated whether a potent humanin analogue S14G-humanin (HNG) would protect against chemotherapy-induced damage to normal cells without interfering with the chemotherapy-induced suppression of cancer cells. Young adult male mice were inoculated iv with murine melanoma cells. After 1 week, cancer-bearing mice were randomized to receive either: no treatment, daily ip injection of HNG, a single ip injection of cyclophosphamide (CP), or CP+HNG and killed at the end of 3 weeks. HNG rescued the CP-induced suppression of leucocytes and protected germ cell from CP-induced apoptosis. Lung metastases were suppressed by HNG or CP alone, and further suppressed by CP+HNG treatment. Plasma IGF-1 levels were suppressed by HNG with or without CP treatment. To investigate whether HNG maintains its protective effects on spermatogonial stem cells, sperm output, and peripheral leucocytes after repeated doses of CP, normal adult male mice received: no treatment, daily sc injection of HNG, 6 ip injections of CP at 5-day intervals, and the same regimens of CP+HNG and killed at the end of 4 weeks of treatment. Cauda epididymal sperm counts were elevated by HNG and suppressed by CP. HNG rescued the CP-induced suppression of spermatogonial stem cells, sperm count and peripheral leucocytes. We conclude that HNG 1) protects CP-induced loss of male germ cells and leucocytes, 2) enhances CP-induced suppression of cancer metastases, and 3) acts as a caloric-restriction mimetic by suppressing IGF-1 levels. Our findings suggest that humanin analogues may be promising adjuvants to chemotherapy.

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“…Mitochondrially translated humanin has 21 amino acids; the one translated in the cytosol is has 24 amino acids [108]. A recent review by Gong et al has described the neuro- and cytoprotective roles of humanin in human conditions such as Alzheimer’s disease, Huntington’s disease, prion disease, atherosclerosis, diabetes, and aging [31]. …”

Section: Historical Aspects Of Numtogenesismentioning

confidence: 99%

Numtogenesis as a mechanism for development of cancer

Singh¹,

Choudhury

Tiwari

2017

Seminars in Cancer Biology

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Transfer of genetic material from cytoplasmic organelles to the nucleus, an ongoing process, has implications in evolution, aging, and human pathologies such as cancer. The transferred mitochondrial DNA (mtDNA) fragments in the nuclear genome are called nuclear mtDNA or NUMTs. We have named the process numtogenesis, defining the term as the transfer of mtDNA into the nuclear genome, or, less specifically, the transfer of mitochondria or mitochondrial components into the nucleus. There is increasing evidence of the involvement of NUMTs in human biology and pathology. Although information pertaining to NUMTs and numtogenesis is sparse, the role of this aspect of mitochondrial biology to human cancers is apparent. In this review, we present available knowledge about the origin and mechanisms of numtogenesis, with special emphasis on the role of NUMTs in human malignancies. We describe studies undertaken in our laboratory and in others and discuss the influence of NUMTs in tumor initiation and progression and in survival of cancer patients. We describe suppressors of numtogenesis and evolutionary conserved mechanisms underlying numtogenesis in cancer. An understanding the emerging field of numtogenesis should allow comprehension of this process in various malignancies and other diseases and, more generally, in human health.

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Humanin and Age-Related Diseases: A New Link?

Cited by 93 publications

References 106 publications

Mitochondrial function in hypoxic ischemic injury and influence of aging

Mitochondrial function in hypoxic ischemic injury and influence of aging

The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice

Numtogenesis as a mechanism for development of cancer

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