It has become amply clear that mitochondrial function defined by quality, quantity, dynamics, homeostasis, and regulated by mitophagy and mitochondrial biogenesis is a critical metric of human aging and disease. As a consequence, therapeutic interventions that can improve mitochondrial function can have a profound impact on human health and longevity. Kisspeptins are neuropeptides belonging to the family of metastasis suppressors that are known to regulate functions like fertility, reproduction, and metabolism. Using SKNSH cell line, hippocampus explant cultures and hippocampus of aging Wistar rat models, we show that Kisspeptin-10 (Kp) induces autophagy and mitophagy via calcium, Ca²⁺/CaM-dependent protein kinase kinase β (CaMKKβ), AMP-activated protein kinase (AMPK), and Unc-51 like autophagy activating kinase (ULK1) signaling pathway that is independent of mammalian target of rapamycin (mTOR). Intriguingly, Kp administration in vivo also results in the enhancement of mitochondrial number, complex I activity, and Adenosine Triphosphate (ATP) levels. This study uncovers potential effects of Kp in protecting mitochondrial health and as a possible therapeutic intervention to hippocampus associated impairments such as memory, cognitive aging, and other diseases linked to mitochondrial dysfunction.

众所周知，线粒体的功能，质量，数量，动力学，体内稳态以及线粒体和线粒体生物发生的调控是人类衰老和疾病的关键指标。因此，可以改善线粒体功能的治疗性干预措施可能对人类健康和长寿产生深远影响。Kisspeptins是属于转移抑制因子家族的神经肽，已知其调控诸如生育，繁殖和代谢等功能。使用SKNSH细胞系，海马外植体培养和衰老Wistar大鼠模型的海马，我们显示Kisspeptin-10（Kp）通过钙，Ca ²⁺诱导自噬和线粒体吞噬。/ CaM依赖性蛋白激酶激酶β（CaMKKβ），AMP激活蛋白激酶（AMPK）和Unc-51像自噬激活激酶（ULK1）信号传导途径，独立于雷帕霉素（mTOR）的哺乳动物靶标。有趣的是，体内施用Kp还可以增强线粒体数量，复合物I活性和三磷酸腺苷（ATP）水平。这项研究揭示了Kp在保护线粒体健康方面的潜在作用，并可能作为治疗海马体相关损伤的潜在干预手段，例如记忆力，认知衰老以及其他与线粒体功能障碍有关的疾病。