Aging & Longevity

In a comprehensive study to decipher the multi-layered response to the chemotherapeutic agent temozolomide (TMZ), we analyzed 427 genomes and determined mutational patterns in a collection of ∼40 isogenic DNA repair-deficient human TK6 lymphoblast cell lines. We first demonstrate that the spontaneous mutational background is very similar to the aging-associated mutational signature SBS40 and mainly caused by polymerase zeta-mediated translesion synthesis (TLS). MSH2-/- mismatch repair (MMR)...

Metaxins are a family of evolutionarily conserved proteins that reside on the mitochondria outer membrane (MOM) and participate in the protein import into the mitochondria. Metaxin-2 (Mtx2), a member of this family, has been identified as a key component in the machinery for mitochondrial transport in both C. elegans and human neurons. To deepen our understanding of Mtx2's role in neurons, we examined the homologous genes CG5662 and CG8004 in Drosophila. The CG5662 is a non-essential gene while...

Chronological age is a crucial risk factor for diseases and disabilities among older adults. However, individuals of the same chronological age often exhibit divergent biological aging states, resulting in distinct individual risk profiles. Chronological age estimators based on omics data and machine learning techniques, known as aging clocks, provide a valuable framework for interpreting molecular-level biological aging. Metabolomics is an intriguing and rapidly growing field of study,...

Aging-associated cardiac hypertrophy (AACH) increases susceptibility to heart failure in the elderly. Chromatin remodeling contributes to the gene reprogramming in AACH; however, the intrinsic regulations remain elusive. We performed a transcriptome analysis for AACH in comparison with pressure-overload-induced pathological cardiac hypertrophy in mice and identified myeloid leukemia factor 1 (MLF1) as an aging-sensitive factor whose expression was reduced during aging but could be reversed by...

Double-strand breaks (DSBs) are a formidable threat to genome integrity, potentially leading to cancer and various genetic diseases. The prolonged lifespan of mammalian oocytes increases their susceptibility to DNA damage over time. While somatic cells suppress DSB repair during mitosis, oocytes exhibit a remarkable capacity to repair DSBs during meiotic maturation. However, the precise mechanisms underlying DSB repair in oocytes remain poorly understood. Here, we describe the pivotal role of...

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Cellular senescence is an aging mechanism characterized by cell cycle arrest and a senescence-associated secretory phenotype (SASP). Preclinical studies demonstrate that senolytic drugs, which target survival pathways in senescent cells, can counteract age-associated conditions that span several organs. The comparative efficacy of distinct senolytic drugs for modifying aging and senescence biomarkers in vivo has not been demonstrated. Here, we established aging- and senescence-related plasma...

Carotenoids are naturally occurring pigments found in plants and certain microorganisms. Some carotenoids act as precursors to vitamin A, which is essential for various health aspects, including vision, immune function, and skin health. Carotenoids, including α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin, are known to reduce the risk of age-related diseases and promote healthy aging. This study examines the relationship between dietary carotenoid levels and biological...

Age-associated loss of muscle mass and function and subsequent mobility decline define poor health outcomes, reduced quality of life, and mortality risk. The rate and extent of aging-related muscle loss varies across older adults. It is challenging to understand the molecular pathogenesis of mobility decline, as anthropometric and imaging techniques, primarily used in muscle function assessment, do not offer much molecular information. Small extracellular vesicles (sEV) are lipid membrane-bound,...

Cognitive aging is described as the age-related decline in areas such as memory, executive function, reasoning, and processing speed. Super-Agers, adults over 80 years old, have cognitive function performance comparable to middle-aged adults. To improve cognitive reserve and potentially decrease Alzheimer's disease (AD) risk, it is essential to contrast changes in regional brain volumes between "Positive-Agers" who have superior cognitive performance compared to their age peers but are not 80...

Sarcopenia and AD are both classic degenerative diseases, and there is growing epidemiological evidence of their comorbidity with aging; however, the mechanisms underlying the biology of their commonality have not yet been thoroughly investigated. APP is a membrane protein that is expressed in tissues and is expressed not only in the nervous system but also in the NMJ and muscle. Deposition of its proteolytic cleavage product, Aβ, has been described as a central component of AD pathogenesis....

CONCLUSIONS: Cognitive impairment was more likely to co-occur with those with low and increasing transport restrictions than with those with moderate and decreasing transport restrictions. Addressing transport restriction among older adults holds the potential to ameliorate cognitive outcomes.

CONCLUSION: Near VI is significantly associated with recurrent hospitalization in older US adults. Future studies should determine whether improving near vision affects the likelihood of recurrent hospitalization.

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Proteomics enables the characterization of brain aging biomarkers and discernment of changes during brain aging. We leveraged multimodal brain imaging data from 10,949 healthy adults to estimate brain age gap (BAG), an indicator of brain aging. Proteome-wide association analysis across 4,696 participants of 2,922 proteins identified 13 significantly associated with BAG, implicating stress, regeneration and inflammation. Brevican (BCAN) (β = -0.838, P = 2.63 × 10^(-)^(10)) and growth...

Fibroblast growth factor 21 (FGF21) is a key regulator of metabolism and cardiovascular health. However, its upregulation in aging and age-related disorders suggests the presence of FGF21 resistance. This study aimed to elucidate the mechanisms underlying senescence-associated FGF21 resistance in human umbilical vein endothelial cells (HUVECs) and to explore potential therapeutic interventions. Transcriptomic analysis revealed a significant reduction in the number of FGF21-regulated genes in...

Neurodegenerative diseases (NDDs) are a group of neurological disorders characterized by the progressive loss of neuronal structure and function, leading to cognitive and behavioral impairments. Despite significant research advancements, there is currently no definitive cure for NDDs. With global aging on the rise, the burden of these diseases is becoming increasingly severe, highlighting the urgency of understanding their pathogenesis and developing effective therapeutic strategies. Microglia,...

The rapid aging of the global population necessitates addressing age-related conditions through innovative strategies. Nutritional supplements have emerged as potential interventions for preventing or slowing age-related changes, with betaine being a promising candidate. This systematic review aims to provide a comprehensive analysis of current literature on the impact of betaine on the aging process. Specifically, we summarize the mechanisms through which betaine is proposed to affect aging, we...

CONCLUSIONS: To ascertain the adequacy of the loneliness measure, it is crucial to customize a new short version of the loneliness scale for Chinese older adults through Rasch analysis.