Aging & Longevity

The global extension of human lifespan has intensified the focus on aging, yet its underlying mechanisms remain inadequately understood. The article highlights aspects of genetic susceptibility to impaired brain bioenergetics, trends in age-related gene expression related to neuroinflammation and brain senescence, and the impact of stem cell exhaustion and quiescence on accelerated brain aging. We also review the accumulation of senescent cells, mitochondrial dysfunction, and metabolic...

Immunotherapy has transformed the landscape of cancer treatment, with T cell-based strategies at the forefront of this revolution. However, the durability of these responses is frequently undermined by two intertwined phenomena: T cell exhaustion and senescence. While exhaustion is driven by chronic antigen exposure in the immunosuppressive tumor microenvironment, leading to a reversible state of diminished functionality, senescence reflects a more permanent, age- or stress-induced arrest in...

The evolutionarily conserved Hippo (Hpo) pathway has been shown to impact early development and tumorigenesis by governing cell proliferation and apoptosis. However, its post-developmental roles are relatively unexplored. Here, we demonstrate its roles in post-mitotic cells by showing that defective Hpo signaling accelerates age-associated structural and functional decline of neurons in Caenorhabditis elegans. Loss of wts-1/LATS, the core kinase of the Hpo pathway, resulted in premature...

A core facet of the National Institute on Aging's mission is to identify pharmacological interventions that can promote human healthy aging and long life. As part of the comprehensive effort toward that goal, the NIA Division of Biology of Aging established the Caenorhabditis Intervention Testing Program (CITP) in 2013. The C. elegans model (with an ~ 21 day lifespan) has led the field in dissection of longevity genetics and offers features that allow for relatively rapid testing and for the...

Phylodynamic inference (PI) quantifies population dynamics and evolutionary trajectories using phylogenetic trees. Single-cell lineage tracing enables phylogenetic tree reconstruction for thousands of cells in multicellular organisms, facilitating PI at the cellular level. However, cell differentiation and somatic evolution challenge the direct application of existing PI frameworks to somatic tissues. We introduce scPhyloX, a computational framework modeling structured cell populations by...

Dysregulated chromatin remodelers have emerged as critical disease targets. However, owing to the pleiotropic functions of chromatin remodelers, the underlying mechanisms of their effects on cancer have been difficult to elucidate. Here, we investigated the helicase lymphoid-specific (HELLS) oncogenic mechanism by identifying a new direct transcriptional target. Using loss or gain experiments, we identified Mitochondrial elongation factor 1 (MIEF1) as a critical target of the HELLS molecular...

Retrotransposable elements (RTEs) are interspersed repetitive sequences that represent a large portion of eukaryotic genomes. Ancestral expansions of RTEs directly contributed to the shaping of these genomes and to the evolution of different species, particularly mammals. RTE activity is tightly regulated by different epigenetic mechanisms but this control becomes compromised as cells age and RTEs are reactivated. This dysregulation of RTEs leads to perturbation of cell function and organ and...

CONCLUSIONS: High-quality trials are needed to clarify the neurobiological impact of music-making, particularly in MCI populations.

This study aimed to investigate the relationship between total antioxidant capacity (TAC) and phenotypic age acceleration (PhenoAgeAccel), a measure of accelerated biological aging, using data from the National Health and Nutrition Examination Survey (NHANES). Data from the 2003-2010 NHANES surveys, encompassing 16,395 participants, were analyzed. Principal component analysis (PCA) was used to reduce data dimensionality. Multivariate logistic regression models were employed to evaluate the...

CONCLUSIONS: Our findings suggest that PA is associated with a better health-related QOL. However, no association was observed between PA and psychological well-being in this population. We found that calisthenics were the most commonly performed and that more physically active older adults performed several types of exercises/sports in addition to calisthenics and walking for longer durations. Since few studies have investigated the types of exercises/sports in this age group, these findings...

The number of patients requiring dialysis therapy continues to increase worldwide because of the lack of effective treatments for chronic kidney disease (CKD). Furthermore, no curative treatments for acute kidney injury (AKI) have been established. The therapeutic effects of human induced pluripotent stem cell-derived nephron progenitor cells (hiPSC-NPCs) on AKI have been reported in mice but not clinically confirmed. There are also no reports examining the therapeutic potential of hiPSC-NPCs on...

CONCLUSIONS: In cohort studies conducted in the United States and Europe, greater wealth was associated with lower mortality, and the association between wealth and mortality appeared to be more pronounced in the United States than in Europe.

Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) contribute to vascular cognitive impairment and dementia (VCID), with aging and hypertension being key risk factors. Mitochondrial oxidative stress is a hallmark of cerebrovascular aging, leading to endothelial dysfunction. This study tests the hypothesis that increased mitochondrial oxidative stress contributes to age-related CMH susceptibility and evaluates the mitochondrial-targeted antioxidative peptide SS-31 (elamipretide)...

Vegetarian diets are increasingly popular worldwide, but their impact on healthy aging in older adults remains unclear. This study examined the association between vegetarian diets and healthy aging among 2,888 healthy older Chinese adults from the Chinese Longitudinal Healthy Longevity Survey. Dietary patterns (vegan, ovo-vegetarian, pesco-vegetarian, omnivorous) were derived from a simplified non-quantitative food frequency questionnaire. Over a median follow-up of 6 years, after accounting...

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CONCLUSION: Different age identities among older adult lead to different identity recognitions, and a positive age identity makes them more willing to participate in society. The government should consider the diversity and complexity of older adult and provide more opportunities for them to participate in social activities in order to improve their quality of life and level of social participation, allowing them to maintain a positive age identity.

The tumor microenvironment (TME) encompasses various cell types, blood and lymphatic vessels, and noncellular constituents like extracellular matrix (ECM) and cytokines. These intricate interactions between cellular and noncellular components contribute to the development of a malignant TME, such as immunosuppressive, desmoplastic, angiogenic conditions, and the formation of a niche for cancer stem cells, but there is limited understanding of the specific subtypes of stromal cells involved in...

With advancing age, the decline in intestinal stem cell (ISC) function can lead to a series of degenerative changes in the intestinal epithelium, a critical factor that increases the risk of intestinal diseases in the elderly. Consequently, there is an urgent imperative to devise effective dietary intervention strategies that target the alterations in senescent ISCs to alleviate senescence-related intestinal dysfunction. The 28-month-old naturally aging mouse model was utilized to discover that...

With advancing age, neurovascular dysfunction manifests as impaired neurovascular coupling (NVC), microvascular rarefaction, and blood-brain barrier (BBB) disruption, contributing to vascular cognitive impairment (VCI). Our previous research established a causal link between vascular senescence induced cerebromicrovascular dysfunction and cognitive decline in accelerated aging models. The present study examines whether chronological aging promotes endothelial senescence, adversely affecting...

Longitudinal investigation of the Apolipoprotein E (APOE) genotype's impact on Alzheimer's disease (AD) biomarker progression, focusing on amyloid beta (Aβ) accumulation and gray matter (GM) atrophy, integrating cognitive decline and baseline levels. Longitudinal florbetapir-PET and T1-weighted MRI data from 100 cognitively normal (CN) and mild cognitive impaired (MCI) participants both with considerable global Aβ accumulation ("high Aβ accumulators") were analyzed using a voxel-wise approach....