npj aging最新文献

Senescence-associated frailty and sarcopenia are global challenges. We here investigated neuronal activity and skeletal muscle biology in senescence-accelerated mouse prone 8 (SAMP8) mice with scalp acupuncture stimulation (SAPS). Excise activity was assessed using rotarod test in the three groups: SAMP8 mice receiving SAPS (SP8-Ap), SAMP8 controls (SP8-C), and senescence-accelerated mouse resistant 1 controls (SR1). SP8-Ap exhibited significantly improved exercise activity compared to SP8-C. SAPS increased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the frontal cortex of SP8-Ap. Monocyte/macrophage infiltration was significantly reduced in the gastrocnemius of SP8-Ap mice, which was associated with reduced expression of various glycogen synthase kinase-3β (GSK3β)-mediated inflammatory genes and increased insulin-like growth factor (IGF)-1 mRNA and phosphorylated AKT. These results indicate that elevation of neurotropic factors in the frontal cortex by SAPS can improve the exercise activity and skeletal muscle status. SAPS may represent a novel therapeutic approach to improve senescence-related frailty.

Older Sub-Saharan African (SSA) migrants often face cumulative stressors that heighten vulnerability with age. Frailty acts as a chronic stressor that reduces quality of life, partly through its association with depression, while social networks may reduce the effect of depression on quality of life. We analysed cross-sectional data from 205 SSA migrants aged 50 years and above in Australia. We tested a moderated mediation model, guided by the Stress Process and Social Buffering frameworks, using structural equation modelling with 5,000 bootstrap resamples. Frailty was positively associated with depression (β = 0.72, p < 0.001), and depression was negatively associated with quality of life (β = -0.54, p < 0.001). Depression mediated the frailty-quality of life relationship (β = -0.38, p < 0.001), while social networks also moderated the depression-quality of life path (β = 0.13, p = 0.004). These findings highlight the psychological and social pathways linking frailty and well-being in later life. Interventions that address both physical and mental health while fostering strong social networks could enhance resilience and improve quality of life among older SSA migrants in Australia.

We investigate the effects of α-Klotho, an anti-aging hormone, on cell proliferation across three tissues with varying regenerative capacities in the context of aging. Using young and old wild-type mice, alongside old heterozygous Klotho-deficient mice, we administered soluble α-Klotho (sKL) daily for 10 weeks to elucidate the impact of α-Klotho deficiency and its supplementation. Our investigation spanned three organs: the small intestine, the kidney, and the heart. We measured cell cycle markers (BrdU, Ki-67, and phospho-histone-3), Sirtuin-1, DNA-damage response pathways (gamma-H2Ax, ATM, CHK2), and the aging phenotypes. Supplementation of sKL significantly enhances proliferative markers and attenuates many aging changes. Mechanistic studies show that sKL acts through the Sirt1-CHK2 pathway to promote cell proliferation. In summary, Klotho deficiency exacerbated aging phenotypes, reduced regenerative capacity, and impaired cellular proliferation. Supplementation with sKL effectively counters these age-related declines across multiple tissues by enhancing cellular proliferation and attenuating aging phenotypes through the Sirt1-CHK2 signaling pathway.

Aneuploid cells are known to increase with age. Previously, we demonstrated an increased number of aneuploid fibroblasts isolated from aged mice due to chromosomal instability (CIN), which is caused by oxidative stress. It is unclear whether this phenomenon also occurs in human cells, which are more resistant to oxidative stress than mouse cells. Here, we found that fibroblasts from aged individuals exhibited an increase in aneuploid cells. The frequency of chromosome missegregation and micronuclei increased in these cells, indicating CIN. A DNA fiber assay revealed the presence of replication stress, accompanied by an increase in 53BP1 nuclear bodies and ultrafine bridges. Increased levels of reactive oxygen species derived from mitochondria, along with reduced mitochondrial membrane potential, imply that these cells experienced oxidative stress due to mitochondrial functional decline. Antioxidant treatment reduced the frequency of chromosome missegregation and micronuclei, suggesting that oxidative stress causes CIN. Oxidative stress also causes replication stress, which precedes CIN. Spindle microtubules were stabilized in fibroblasts from aged individuals, which was alleviated by antioxidant treatment. Taken together, these findings suggest that aging-related CIN in human fibroblasts is caused by oxidative stress associated with mitochondrial dysfunction, which induces replication stress that in turn causes CIN through microtubule stabilization. Although human fibroblasts are more resistant to the ambient oxygen environment than mouse fibroblasts, our findings showed that they undergo oxidative stress that causes CIN with age in a manner similar to mouse fibroblasts, revealing a conserved phenomenon in mammalian cells.

Age-associated decline in tissue NAD⁺ levels contribute to functional impairments, recognized as aging. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme crucial for NAD⁺ biosynthesis in mammals, is encapsulated in extracellular vesicles (EVs) and secreted into the bloodstream. The importance of extracellular NAMPT-containing EVs (eNAMPT-EVs) in hypothalamic NAD⁺ biosynthesis has been demonstrated in several mouse models. However, whether eNAMPT-EVs derived from human plasma can also act as a physiological NAD⁺ booster remains unclear. Here we show that administration of human plasma-derived, highly purified eNAMPT-EVs can elevate hypothalamic NAD⁺ levels in mice. Furthermore, eNAMPT-EV administration led to an increase in body temperature and suppression of hypothalamic Npy gene expression. These responses were negated by pharmacological NAMPT inhibition. We also found that exercise increases in plasma eNAMPT and hypothalamic NAD⁺ levels. These findings suggest that enhancing circulating eNAMPT-EVs can be an effective strategy for NAD⁺ boosting and potentially an effective anti-aging intervention in humans.

Collagen supplementation has gained attention with increasing claims regarding its beneficial effects on healthy aging based on clinical observations and lifespan extension in pre-clinical models; however, how and which part of an ingested collagen promotes healthy longevity is unknown. Here, we identified the minimal required unit of ingested collagen, which consists of the proper ratio of three glycine to one proline to one hydroxyproline that was sufficient to increase the motility-healthspan and lifespan of C. elegans, as well as collagen homeostasis in human fibroblasts in vitro. Supplementation in 20-month-old mice improved grip strength and prevented age-related fat accumulation. In a clinical observational trial (ISRCTN93189645, 03.07.2025), oral supplementation in humans demonstrated improved skin features within three months and a reduction in biological age by 1.4 years (p = 0.04) within 6 months. Thus, a ratio of three amino acids elicits evolutionarily conserved health benefits from ingested collagens.

Obstructive sleep apnea (OSA) accelerates cardiovascular aging through intermittent hypoxia (IH). We exposed mice to 22 months of IH, modeling lifelong OSA. Compared to controls, IH mice exhibited higher mortality, elevated blood pressure, impaired systolic and diastolic function, vascular stiffening, reduced coronary reserve, and ECG abnormalities. These findings suggest that chronic IH significantly exacerbates cardiovascular decline with aging, underscoring the importance of early OSA diagnosis and intervention.

Social isolation and poor nutrition are recognized risk factors for cognitive decline in older adults. However, the relationship between solitary eating, brain structure, and dietary patterns remains unclear. This study investigated the relationship between solitary eating, brain structure, and diet in healthy older Japanese adults. A total of 727 cognitively normal participants (mean age 70.32 years) underwent MRI and dietary assessments. Results showed that individuals who frequently eat alone have reduced brain volumes in regions critical for cognitive function, particularly the medial temporal lobe and hippocampus. These individuals also demonstrated less healthy dietary patterns, characterized by higher sugar and alcohol consumption, with lower intake of proteins, vitamins, and minerals. Analysis revealed that the difference in hippocampal volume between solitary and social eaters diminished when accounting for dietary factors, suggesting that nutritional factors primarily drive this relationship. However, the difference in medial temporal lobe volume remained significant after dietary adjustment, indicating that other factors, such as reduced social interaction, may affect this region. These findings emphasize the importance of social eating for maintaining brain health in older adults, suggesting that both social and nutritional aspects of eating are crucial. This research provides insights for developing healthy aging strategies that address both social and nutritional dimensions of eating behavior.

The reproductive division of labor defines eusocial insects like ants, where queens reproduce and workers remain sterile. Yet, some workers retain rudimentary ovaries, raising questions about latent reproductive potential. We examined morphological and transcriptomic differences in Pogonomyrmex barbatus queen and worker ovaries at different maturation stages and social contexts. Queens had large, yolk-rich oocytes, while worker ovaries showed regression. Callow workers (<5 days) had more developed ovaries than mature ones (>20 days), suggesting age-related regression, even without reproduction. Queenless workers exhibited greater ovarian regression than queenright ones, indicating factors beyond queen presence may limit reproductive activation. We found ~2000 caste-specific differentially expressed genes, including those involved in metabolism, hormonal signaling, and epigenetic regulation. Queenless workers upregulated a fertility-linked gene and downregulated lipid metabolism genes. Our results show that age and social environment influence ovarian state, highlighting complex regulation of reproductive suppression and offering insight into reproductive senescence in eusocial systems.