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Reproductive aging is a major cause of fertility decline, attributed to decreased oocyte quantity and developmental potential. A possible cause is aging of the surrounding follicular somatic cells that support oocyte growth and development by providing nutrients and regulatory factors. Here, by creating chimeric follicles, whereby an oocyte from one follicle was transplanted into and cultured within another follicle whose native oocyte was removed, we show that young oocytes cultured in aged...

Aging is a major risk factor for cancer, but the precise mechanism by which aging promotes carcinogenesis remains largely unknown. Here, using genetically modified mouse models, we show that p16^(high) senescent (p16^(h)-sn) fibroblasts accumulate with age, constitute inflammatory cancer-associated fibroblasts (CAFs) and promote tumor growth in bladder cancer models. Single-cell RNA sequencing of fibroblasts from aged mice revealed higher expression of the C-X-C motif chemokine 12 gene (Cxcl12)...

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on...

CONCLUSION: MCR may be considered a predictive factor for long-term cognitive impairment and dementia. This should be taken into consideration when clinically evaluating the risk of cognitive impairment and dementia but further research is required to lend greater clarity to this association.

Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45^(+)lineage^(-)CD90.2^(+)NK1.1^(-)NKp46^(-)ST2^(-)KLRG1^(+)IL-17RB^(+) memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P...

Phosphorus magnetic resonance spectroscopy (^(31)P-MRS) is applied for non-invasive studies of neuroenergetic metabolism in neurodegenerative diseases. However, the findings are inconsistent and have not yet been tested in meta-analyses. To address this gap, we performed a systematic review of 29 studies and conducted meta-analyses for 9 studies on Alzheimer's disease (AD, n = 140 patients), 9 studies on Parkinson's disease (PD, n = 183 patients), 3 studies on Progressive Supranuclear Palsy...

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory impairment and cognitive dysfunction, which eventually leads to the disability and mortality of older adults. Although the precise mechanisms by which age promotes the development of AD remains poorly understood, mitochondrial dysfunction plays a central role in the development of AD. Currently, there is no effective treatment for this debilitating disease. It is well accepted that exercise exerts...

Neurological disorders and pain are prevalent clinical issues that severely impact patients' quality of life and daily functioning. With the advancing exploration of these disease mechanisms, G protein-coupled receptor 37 (GPR37) has emerged as a critical protein, garnering widespread attention in the scientific community. As a member of the G protein-coupled receptor family, GPR37 features a seven-transmembrane helix structure and is widely expressed in various brain regions, including the...

Extreme longevity in humans is known to be a heritable trait. In a well-established twin erythrocyte metabolomics and proteomics database, we identified the longevity factor spermidine and a cluster of correlated molecules with high heritability estimates. Erythrocyte spermidine is 82% heritable and significantly correlated with 59 metabolites and 22 proteins. Thirty-eight metabolites and 19 proteins were >20% heritable, with a mean heritability of 61% for metabolites and 49% for proteins....

There is documented sex disparity in cutaneous melanoma incidence and mortality, increasing disproportionately with age and in the male sex. However, the underlying mechanisms remain unclear. While biological sex differences and inherent immune response variability have been assessed in tumor cells, the role of the tumor-surrounding microenvironment, contextually in aging, has been overlooked. Here, we show that skin fibroblasts undergo age-mediated, sex-dependent changes in their proliferation,...

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory impairment and cognitive dysfunction, which eventually leads to the disability and mortality of older adults. Although the precise mechanisms by which age promotes the development of AD remains poorly understood, mitochondrial dysfunction plays a central role in the development of AD. Currently, there is no effective treatment for this debilitating disease. It is well accepted that exercise exerts...

Disruption of circadian rhythms contributes to deficits in cognitive functions during aging. Up to date, the biochemical, molecular and chronobiological bases of such deterioration have not been completely elucidated. Here, we aim: 1) to investigate the endogenous nature of 24 h-rhythms of antioxidant defenses, oxidative stress, clocḱ's, and neurotrophic factors expression, in the rat temporal cortex (TC), and 2) to study the consequences of aging on the circadian organization of those factors....

Tau interacts with α-Synuclein (α-Syn) and co-localizes with it in the Lewy bodies, influencing α-Syn pathology in Parkinson's disease (PD). However, whether these biochemical events regulate α-Syn pathology spreading from the gut into the brain remains incompletely understood. Here, we show that α-Syn and Tau co-pathology is spread into the brain in gut-inducible SYN103^(+/-) and/or TAU368^(+/-) transgenic mouse models, eliciting behavioral defects. Gut pathology was initially observed, and...

Salivary gland branching morphogenesis is regulated by the functional integration of neuronal signaling, but the underlying mechanisms are not fully understood in aging accelerated klotho-deficient (Kl^(-/-)) mice. Here, we investigated whether the neuropeptides substance P (SP) and neuropeptide Y (NPY) affect the branching morphogenesis of embryonic salivary glands in aging Kl^(-/-) mice. In the salivary glands of embryonic Kl^(-/-) mice, morphological analysis and immunostaining revealed that...

The dysfunction of blood-vessel-lining endothelial cells is a major cause of mortality. Although endothelial cells, being present in all organs as a single-cell layer, are often conceived as a rather inert cell population, the vascular endothelium as a whole should be considered a highly dynamic and interactive systemically disseminated organ. We present here a holistic view of the field of vascular research and review the diverse functions of blood-vessel-lining endothelial cells during the...

CONCLUSION: This study represents the largest investigation to date of genome-wide DNA methylation changes and aging in a single tissue, providing valuable insights into primary molecular changes relevant to chronological and biological aging.

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