OBJECTIVE: To explore the mechanism of acupuncture on improving ovarian hypofunction in aged rats from two perspectives: the overall regulation of the hypothalamic-pituitary-ovarian (HPO) axis and the local ovarian follicle stimulating hormone (FSH)/cyclic adenosine monophosphate (cAMP) signaling pathway. METHODS: Six 3-month-old female SPF-grade Sprague-Dawley (SD) rats were selected as the blank group. Another twelve 9-month-old female SD rats were randomly divided into a model group and an acupuncture group, with six rats in each. The acupuncture group received acupuncture at "Baihui" (GV20), "Guanyuan" (CV4), and bilateral "Ciliao" (BL32) for 20 min per session, once every other day, for a total of 10 sessions. Vaginal smear tests were performed daily to observe the estrous cycle of the rats. Ovarian morphology was observed using HE staining, and follicles at various stages were counted. ELISA was used to detect levels of serum FSH, luteinizing hormone (LH), estradiol (E₂), anti-müllerian hormone (AMH), hypothalamic gonadotropin-releasing hormone (GnRH), pituitary FSH and LH, and ovarian cAMP. Immunohistochemistry and Western blot were used to detect the protein expression of ovarian cAMP protein kinase catalytic subunit, FSH receptor (FSHR), and P450. Real-time quantitative PCR was used to measure mRNA expression levels of FSHR and P450 in ovarian tissue. RESULTS: Compared with the blank group, the model group showed an increased rate of estrous cycle disorder (P<0.01), reduced granulosa cell layers with blurred boundaries and disordered arrangement, decreased numbers of developing follicles at all stages, and increased numbers of atretic follicles (P<0.01); the serum levels of FSH and LH were increased (P<0.01), while E₂ and AMH levels were decreased (P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were elevated (P<0.01), and ovarian cAMP level was decreased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were reduced (P<0.01), and ovarian FSHR and P450 mRNA expression was decreased (P<0.01). Compared with the model group, the acupuncture group showed a reduced rate of estrous cycle disorder (P<0.01), clear granulosa cell margins, increased numbers of primordial and secondary follicles, and decreased numbers of atretic follicles (P<0.01); the serum FSH and LH levels were decreased (P<0.01, P<0.05), while E₂ and AMH levels were increased (P<0.05, P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were decreased (P<0.01, P<0.05), and ovarian cAMP level was increased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were elevated (P<0.01), and ovarian FSHR and P450 mRNA expression was increased (P<0.01). CONCLUSION Acupuncture could delay ovarian hypofunction in aged rats, possibly through regulating the HPO axis and the FSH/cAMP signaling pathway.
Animals ; Female ; Rats ; Rats, Sprague-Dawley ; Follicle Stimulating Hormone/genetics* ; Acupuncture Therapy ; Ovary/metabolism* ; Signal Transduction ; Humans ; Cyclic AMP/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Aging/metabolism* ; Hypothalamus/metabolism* ; Pituitary Gland/metabolism* ; Gonadotropin-Releasing Hormone/metabolism*

Based on the theory of the five-body constituents from Huangdi Neijing (Yellow Emperor's Internal Classic), the approach and methods of acupuncture for facial aging are explored. Acupuncture for facial aging can be guided by the concept of the five-body constituents, targeting the facial "skin, flesh, vessels, tendons, and bones", and utilizing five different types of needles-facial needles, needle knives, filiform needles, retaining needles, and elongated needles and filiform needles-to maximize their respective advantages in treating facial aging. Facial needles are applied to the "skin" by selecting facial acupoints or local ashi points (at wrinkle or pigmentation sites). Needle knives are used for the "flesh" to perform longitudinal dredging and transverse dissection of the facial muscle layers. Filiform needles target the "vessels" with needling at Renying (ST9) to improve facial complexion. Retaining needles act on the "tendons" with needling from Taiyang (EX-HN5) to Xiaguan (ST7), and Jiache (ST6) to Daying (ST5), using clockwise twisting to generate a retaining needle sensation and lifting to achieve an overall facial lifting effect.
Humans ; Acupuncture Therapy/methods* ; Face ; Skin Aging ; Acupuncture Points ; Aging

Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.
Humans ; Sleep Apnea, Obstructive/pathology* ; Aging/physiology* ; Oxidative Stress/physiology* ; Animals

Aging is an inevitable, physiological process of the human body, leading to deterioration in bodily function and increased susceptibility to various diseases. Effective endogenous therapeutic strategies for anti-aging and related diseases remain limited. Exercise confers multifaceted benefits to physical health by augmenting osteogenic and myogenic processes, enhancing cardiovascular and nervous system function, and attenuating chronic inflammation. Angiogenesis and lymphangiogenesis play pivotal roles in anti-aging, tissue repair, and immune response modulation, underscoring their potential as therapeutic targets for age-related diseases. Modulating angiogenic and lymphangiogenic pathways may provide a promising strategy for mitigating vascular decline and immune system dysfunction associated with aging. Exercise-induced endogenous angiogenesis and lymphangiogenesis can exert beneficial effects on physiological function, thereby representing a potential therapeutic paradigm for combating age-related decline and diseases. This review offers a thorough summary of the present knowledge regarding angiogenesis and lymphangiogenesis induced by exercise, encompassing the underlying mechanisms and the effects in different organs. In addition, it explores the potential of physical activity as a non-pharmacological intervention for anti-aging strategies and disease management, offering novel insights into the intersection of physical activity, aging, and disease progression.
Humans ; Lymphangiogenesis/physiology* ; Aging/physiology* ; Exercise/physiology* ; Animals ; Neovascularization, Physiologic/physiology* ; Angiogenesis

Mitochondria serve as multifunctional powerhouses within cells, coordinating essential biological activities that are critical for cell viability, including material metabolism, signal transduction, and the maintenance of homeostasis. They support cells in adapting to complex and fluctuating environments. Oocytes, being the largest cells in multicellular organisms, contain a high number of mitochondria with unique structural characteristics. Mitochondria play active roles in the development and maturation of oocytes. A decline in mitochondrial function negatively affects both the quality and quantity of oocytes, thereby contributing to ovarian aging. However, the specific mechanisms through which mitochondrial dysfunction influences the progression of ovarian aging and impacts reproductive longevity remain unclear. Furthermore, medical strategies aimed at rejuvenating mitochondria to restore ovarian reserve and improve female reproductive potential may open new avenues for clinical treatment. In this review, we summarize the current understanding and key evidence regarding the role of mitochondrial dysfunction in ovarian aging and present emerging medical approaches targeting mitochondria to alleviate premature ovarian aging and enhance reproductive performance.
Humans ; Female ; Mitochondria/physiology* ; Ovary/physiology* ; Aging/physiology* ; Animals ; Oocytes/metabolism*

Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

The increasing prevalence of aging has led to a rising incidence of comorbidity of sarcopenia and obesity, posing significant burdens on socioeconomic and public health. Current research has systematically explored the pathogenesis of each condition; however, the mechanisms underlying their comorbidity remain unclear. This study reviews the current literature on sarcopenia and obesity in the aging population, focusing on their shared biological mechanisms, which include loss of autophagy, abnormal macrophage function, mitochondrial dysfunction, and reduced sex hormone secretion. It also identifies metabolic mechanisms such as insulin resistance, vitamin D metabolism abnormalities, dysregulation of iron metabolism, decreased levels of nicotinamide adenine dinucleotide, and gut microbiota imbalances. Additionally, this study also explores the important role of genetic factors, such as alleles and microRNAs, in the co-occurrence of sarcopenia and obesity. A better understanding of these mechanisms is vital for developing clinical interventions and preventive strategies.
Humans ; Sarcopenia/physiopathology* ; Obesity/physiopathology* ; Aging/physiology* ; Autophagy/physiology* ; Insulin Resistance ; Comorbidity ; Vitamin D/metabolism* ; Gonadal Steroid Hormones/metabolism* ; Gastrointestinal Microbiome ; Mitochondria ; MicroRNAs

This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Apoptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Animals ; Rats ; Humans ; Molecular Docking Simulation ; Aging/metabolism* ; Protein Interaction Maps/drug effects* ; Heart/drug effects* ; Network Pharmacology

Heart rate variability time and frequency indices are widely used in functional assessment for autonomic nervous system (ANS). However, this method merely analyzes the effect of cardiac dynamics, overlooking the effect of cardio-pulmonary interplays. Given this, the present study proposes a novel cardiopulmonary coupling (CPC) algorithm based on cross-wavelet transform to quantify cardio-pulmonary interactions, and establish an assessment system for ANS aging effects using wearable electrocardiogram (ECG) and respiratory monitoring devices. To validate the superiority of the proposed method under nonstationary and low signal-to-noise ratio conditions, simulations were first conducted to demonstrate the performance strength of the proposed method to the traditional one. Next, the proposed CPC algorithm was applied to analyze cardiac and respiratory data from both elderly and young populations, revealing that young populations exhibited significantly stronger couplings in the high-frequency band compared with their elderly counterparts. Finally, a CPC assessment system was constructed by integrating wearable devices, and additional recordings from both elderly and young populations were collected by using the system, completing the validation and application of the aging effect assessment algorithm and the wearable system. In conclusion, this study may offers methodological and system support for assessing the aging effects on the ANS.
Humans ; Autonomic Nervous System/physiology* ; Algorithms ; Aging/physiology* ; Electrocardiography/methods* ; Heart Rate/physiology* ; Wavelet Analysis ; Aged ; Signal Processing, Computer-Assisted ; Wearable Electronic Devices