Aging & Longevity

Testicular aging is associated with declining reproductive health, but the molecular mechanisms are unclear. Here we generate a dataset of 214,369 single-cell transcriptomes from testicular cells of 35 individuals aged 21-69, offering a resource for studying testicular aging and physiology. Machine learning analysis reveals a stronger aging response in somatic cells compared to germ cells. Two waves of aging-related changes are identified: the first in peritubular cells of donors in their 30s,...

Understanding the key drivers of brain aging is essential for effective prevention and treatment of neurodegenerative diseases. Here, we integrate human brain and physiological data to investigate underlying mechanisms. Functional MRI analyses across four large datasets (totaling 19,300 participants) show that brain networks not only destabilize throughout the lifetime but do so along a nonlinear trajectory, with consistent temporal "landmarks" of brain aging starting in midlife (40s)....

Rnd3 is a small Rho-GTPase that has been implicated in various cardiovascular diseases. Yet, its role in diabetes-induced cardiomyocyte senescence remains unknown. Here we tested the role of Rnd3 in cardiomyocyte senescence and diabetic cardiomyopathy (DCM). The expression of Rnd3 was found to be reduced in peripheral blood mononuclear cells from diabetic patients and correlated negatively with age but positively with cardiac function. In 96-week-old Sprague Dawley (SD) rats, cardiac function...

The aging population, defined as individuals 65 years or older, is rapidly increasing, with age as the most significant and independent risk factor for cardiovascular diseases (CVD). Older women show greater susceptibility to cardiac remodeling and dysfunction compared to men. Despite this, the specific molecular drivers of sex differences in cardiac aging remain poorly understood. In this study, cardiac fibrosis and gene expression profiles were investigated in left atrial appendage samples...

CONCLUSIONS AND IMPLICATIONS: The risk of all-cause mortality declined among older adults with a reversal of frailty. Hemoglobin concentration and exercise contributed to the reversal of frailty among older adults. In contrast, aging, long daily sedentary time, cigarette smoking, and illiteracy were risk factors for the reversal of frailty. These findings may provide better strategies for frailty intervention.

Haemophilia A and B are congenital X-linked bleeding disorders resulting from deficiencies in clotting factors VIII (haemophilia A) and IX (haemophilia B). Patients with severe deficiency, defined as having less than 1% of normal plasma factor activivity, often have spontaneous bleeding within the first few years of life. Those with moderate and mild deficiencies typically present with post-traumatic or post-surgical bleeding later in life. A high index of suspicion and measurement of factor...

Recent studies have reported that the spaceflight environment lengthens leukocyte telomeres. We propose that this baffling finding reflects changes in the composition of leukocyte subsets rather than an actual increase in telomere length within individual leukocytes. Since leukocyte telomere length is associated with aging-related diseases and longevity in humans, it is crucial to understand the underlying factors driving telomere length changes in space.

CONCLUSIONS: Neuropsychiatric symptoms occur commonly in MCI participants, and are mainly related to defect of language and memory function. A better understanding of the relationship between specific cognition and NPS may alert clinicians to pay close attention to the NPS in MCI patient, which may need early intervention.

CONCLUSION: Elevated late-life cholesterol may protect cognitive function in healthy individuals and those with mild impairment, with a sex-specific impact in dementia, beneficial for women but detrimental for men.

CONCLUSIONS: We developed an explainable machine learning model to predict SO in aging community and nursing populations. This model offers a novel, accessible, and interpretable approach to SO prediction with potential to enhance early detection and intervention strategies. Further studies are warranted to validate our model in diverse populations and evaluate its impact on patient outcomes when integrated into comprehensive geriatric assessments.

Retinoic acid (RA) is a standard-of-care neuroblastoma drug thought to be effective by inducing differentiation. Curiously, RA has little effect on primary human tumors during upfront treatment but can eliminate neuroblastoma cells from the bone marrow during post-chemo maintenance therapy-a discrepancy that has never been explained. To investigate this, we treat a large cohort of neuroblastoma cell lines with RA and observe that the most RA-sensitive cells predominantly undergo apoptosis or...

Senescence-associated secretory phenotype (SASP) mediates the biological effects of senescent cells on the tissue microenvironment and contributes to ageing-associated disease progression. ACSS2 produces acetyl-CoA from acetate and epigenetically controls gene expression through histone acetylation under various circumstances. However, whether and how ACSS2 regulates cellular senescence remains unclear. Here, we show that pharmacological inhibition and deletion of Acss2 in mice blunts SASP and...

The brain is a high-energy tissue, and although aging is associated with dysfunctional inflammatory and neuron-specific functional pathways, a direct connection to metabolism is not established. Here, we show that isoforms of mitochondrial regulator PGC-1α are driven from distinct brain cell-type specific promotors, repressed with aging, and integral in coordinating metabolism and growth signaling. Transcriptional and proteomic profiles of cortex from male adult, middle age, and advanced age...

The accuracy of protein synthesis and its relation to ageing has been of long-standing interest. To study whether spontaneous changes in the rate of ribosomal error occur as a function of age, we first determined that stop-codon readthrough is a more sensitive read-out of mistranslation due to codon-anticodon mispairing than missense amino acid incorporation. Subsequently, we developed knock-in mice for in-vivo detection of stop-codon readthrough using a gain-of-function Kat2-TGA-Fluc...

Human lifespan is shaped by genetic and environmental factors. To enable precision health, understanding how genetic variants influence mortality is essential. We conducted a survival analysis in European ancestry participants of the UK Biobank, using age-at-death (N=35,551) and last-known-age (N=358,282). The associations identified were predominantly driven by cancer. We found lifespan-associated loci (APOE, ZSCAN23) for common variants and six genes where burden of loss-of-function variants...

Neurogenesis and gliogenesis continue in the ventricular-subventricular zone (V-SVZ) of the adult rodent brain. V-SVZ astroglial cells with apical contact with the ventricle (B1 cells) function as neural stem cells (NSCs). B1 cells sharply decline during early postnatal life; in contrast, neurogenesis decreases at a slower rate. Here, we show that a second population of astroglia (B2 cells) that do not contact the ventricle also function as NSCs in the adult mouse brain. B2 cell numbers increase...

The buildup of knot-like RNA structures in brain cells may be the key to understanding how uncontrolled protein aggregation drives Alzheimer's disease.

Age and elevated intraocular pressure (IOP) are the two major risk factors for developing glaucoma, a leading cause of blindness worldwide that is characterized by the loss of retinal ganglion cells (RGCs). Although vision loss is irreversible over the long term, accumulating evidence points to short-term improvement of vision in glaucoma patients in response to certain interventions, suggesting that RGCs have the capacity to recover function. In the present study, we sought to investigate the...

This study investigates the impact of postretirement organizational work on the well-being and overall quality of life of the elderly population in Cyprus. Specifically, it evaluates the multifaceted effects of continued employment after retirement, based on data collected through a survey administered to a representative sample of elderly Cypriots. The research findings, informed by prominent instruments in the field, demonstrate significant enhancements in autonomy, self-actualization, and...

The choroid plexus (CP) serves as the primary source of cerebrospinal fluid (CSF). The blood-CSF barrier, composed of tight junctions among the epithelial cells in the CP, safeguards CSF from unrestricted exposure to bloodborne factors. This barrier is thus indispensable to brain homeostasis and is associated with age-related neural disorders. Nevertheless, its aging is poorly understood. Here, we report that cathepsin S (CTSS), a protease secreted from the CP macrophages, is upregulated in aged...