Aging & Longevity

How central and peripheral circadian clocks regulate protein metabolism and affect tissue mass homeostasis has been unclear. Circadian shifts in the balance between anabolism and catabolism control muscle growth rate in young zebrafish independent of behavioral cycles. Here, we show that the ubiquitin-proteasome system (UPS) and autophagy, which mediate muscle protein degradation, are each upregulated at night under the control of the muscle peripheral clock. Perturbation of the muscle...

Cerebral small vessel disease (cSVD) refers to all pathologies of the brain's arterioles, capillaries, and venules. cSVD is highly prevalent with ageing and is diagnosed by its characteristic neuro-imaging features. Emerging evidence suggests that circulating immune cells play an important role in cSVD's pathology. However, the specific immune cell populations involved remain poorly understood. This systematic review synthesizes current evidence on circulating immune cells in cSVD and their...

Despite significant advances in aging research, translating these findings into clinical practice remains a challenge. Aging is a complex, multifactorial process shaped by many factors including genetic, metabolic, and environmental factors. While medical advancements have extended lifespan, healthspan remains constrained by cellular senescence, telomere attrition, and systemic inflammation-core hallmarks of biological aging. However, emerging evidence suggests that telomere dynamic is not...

The neuronal tissue is notable for its unique regulation of the immune system, response to DNA damage, endurance against reactive oxygen and nitrogen species, and control of inflammatory pathways. Here, I discuss some uniqueness of the brain's aging process in light of the free radical theory of aging, DNA-damage accumulation, inflammaging, and aging as a consequence of a programmed developmental process. Key points include (i) the resilience of the neuronal tissue to oxidative stress; (ii) the...

Identifying novel compounds with therapeutic potential is a main area of interest in biomedical research. Tetrahydroindenoindole (THII) has emerged as a compound of interest due to both its antioxidant properties and its action as a pharmacological activator of the enzyme cytochrome b(5) reductase 3. However, there is a lack of comprehensive synthesis of findings, particularly concerning the effects of THII on metabolism in mice under non-disease conditions. This systematic review with...

Aging research is often framed within pluralistic frameworks that emphasize cellular and molecular damage processes. Among the most influential are Strategies for Engineered Negligible Senescence (SENS), which aims to counteract biological decline through targeted damage repair, and the Hallmarks of Aging (HoA), which seeks to identify fundamental mechanisms underlying this process. Both proposals, although diverse, significantly influence contemporary approaches to the challenges posed by...

Sphingolipids (SPLs) are essential membrane lipids with significant bioactive roles involved in various cellular processes, and their alterations have been found to be linked to many diseases, including age-related diseases. However, comprehensive studies on the association of plasma sphingolipids with aging in large, diverse cohorts remain limited. The objective of this study was to investigate the relationship between plasma sphingolipid levels and aging in a cohort of 240 normoglycemic,...

CONCLUSION: In postmenopausal osteoporotic women, the CC was positively and independently associated with denosumab treatment response.

Degradation of proteostasis, mitochondrial function, and cellular stress resistance results in a build-up of damaged proteins, oxidative insult, and chronic inflammation, characteristic of aging. CHIP is essential for maintaining protein quality control and cellular homeostasis by having dual E3 ubiquitin ligase and co-chaperone activities. CHIP facilitates proteostasis by maintaining proteostasis in misfolded, aggregated proteins by promoting their degradation. Mitochondrial dysfunction,...

Maintaining genomic stability is essential for detecting DNA damage and activating appropriate responses such as repair, apoptosis, or senescence, primarily mediated by the ATM-p53 axis. ATM is the main sensor of double-strand breaks, and once activated, it will either promote the repair of damaged DNA or eliminate the damaged cells through apoptosis. ATM and p53 mutations upset this equilibrium to cause genomic instability, therapy resistance, and tumor progression in the context of cancer....

Retrotransposable elements (RTEs) have been implicated in the pathogenesis of several age-associated diseases. Although model systems indicate that age- and sex-dependent loss of heterochromatin increases RTE expression, data from large human studies are lacking. Here we assessed the expression levels of 795 blood RTE subfamilies in 2467 participants of the population-based Rhineland Study. We found that the expression of more than 98% of RTE subfamilies increased with both chronological and...

Mitochondria supply most of the energy for cellular functions and coordinate numerous cellular pathways. Their dynamic nature allows them to adjust to stress and cellular metabolic demands, thus ensuring the preservation of cellular homeostasis. Loss of normal mitochondrial function compromises cell survival and has been implicated in the development of many diseases and in aging. Although exposure to continuous or severe stress has adverse effects on cells, mild mitochondrial stress enhances...

CONCLUSION: Resistance training is the most effective exercise modality for enhancing overall cognitive function and inhibitory control in older adults. Physical-mental training offers the greatest benefits for improving working memory and task-switching ability, while aerobic exercise is most beneficial for enhancing memory function. Based on these findings, the recommended exercise protocols are: Resistance Training: 12 weeks, 2-3 times per week, 45 min per session. Aerobic Exercise: 21 weeks,...

Aging is characterized by a steady loss of physiological integrity, leading to impaired function and increased vulnerability to death. Cell senescence is a biological process that progresses with aging and is believed to be a key driver of age-related diseases. Senescence, a hallmark of aging, also demonstrates its beneficial physiological aspects as an anti-cancer, pro-regenerative, homeostatic, and developmental mechanism. A transitory response in which the senescent cells are quickly formed...

Several bat species live >20-40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigate the requirements for malignant transformation in primary fibroblasts from four bat species Myotis lucifugus, Eptesicus fuscus, Eonycteris spelaea, and Artibeus jamaicensis - spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence, express active telomerase, and show attenuated...

Therapy-induced senescence (TIS) is a major challenge in cancer therapy as senescent cancer cells provoke local and systemic inflammation and might be the cause of recurrences. Elucidation of pathways leading to TIS is of utmost importance for establishing strategies to counteract this. Previously we have shown that temozolomide (TMZ), an alkylating drug used forefront in glioma therapy, causes majorly cellular senescence, which is triggered by the primary damage O⁶-methylguanine, activating the...

Age-related changes in sleep have been associated with cognitive decline, yet causal pathways have not been identified. Evidence suggests reduced cardiovascular health may be a consequence of poor sleep and a precursor to cognitive decline. This observational cohort study used path analyses to determine whether cardiovascular disease risk mediated or moderated effects of sleep on yearly longitudinal change in cognition, estimated with linear growth models. Total sleep time (TST), sleep...

CONCLUSIONS AND IMPLICATIONS: Mexican American older adults with multimorbidity and high HGS had a 30% decreased risk of falls over time. Increasing muscle strength through exercise may help prevent falls among those with multimorbidity.

Most genetic conditions are described in pediatric populations, leaving a gap in understanding their clinical progression and management in adulthood. Motivated by other applications of large language models (LLMs), we evaluated whether Llama-2-70b-chat (70b) and GPT-3.5 (GPT) could generate plausible medical vignettes, patient-geneticist dialogues and management plans for a hypothetical child and adult patients across 282 genetic conditions (selected by prevalence and categorized based on...

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