Aging & Longevity

Trigonelline is an NAD(+) precursor that improves muscle function during ageing and is reduced in human sarcopenia

3 weeks 4 days ago
Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD^(+)) levels are hallmarks of skeletal muscle ageing and sarcopenia^(1-3), but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid⁴, NAD^(+) levels and muscle health in multiple species. In humans, serum trigonelline levels...
Mathieu Membrez

Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis

3 weeks 4 days ago
Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.0-27.9 kg/m² ), to 25% CR or ad-libitum (AL) control (2:1) for 2 years. Prior analyses of CALERIE™ participants' blood chemistries, immunology, and epigenetic data suggest the 2-year CR...
Waylon J Hastings

Genetic and pharmacological modulation of lamin A farnesylation determines its function and turnover

3 weeks 4 days ago
Hutchinson-Gilford Progeria syndrome (HGPS) is a severe premature ageing disorder caused by a 50 amino acid truncated (Δ50AA) and permanently farnesylated lamin A (LA) mutant called progerin. On a cellular level, progerin expression leads to heterochromatin loss, impaired nucleocytoplasmic transport, telomeric DNA damage and a permanent growth arrest called cellular senescence. Although the genetic basis for HGPS has been elucidated 20 years ago, the question whether the Δ50AA or the permanent...
Mattheus Xing Rong Foo

Contrasting somatic mutation patterns in aging human neurons and oligodendrocytes

3 weeks 5 days ago
Characterizing somatic mutations in the brain is important for disentangling the complex mechanisms of aging, yet little is known about mutational patterns in different brain cell types. Here, we performed whole-genome sequencing (WGS) of 86 single oligodendrocytes, 20 mixed glia, and 56 single neurons from neurotypical individuals spanning 0.4-104 years of age and identified >92,000 somatic single-nucleotide variants (sSNVs) and small insertions/deletions (indels). Although both cell types...
Javier Ganz

Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

3 weeks 5 days ago
The potential of immune checkpoint inhibitors (ICI) may be limited in situations where immune cell fitness is impaired. Here, we show that the efficacy of cancer immunotherapies is compromised by the accumulation of senescent cells in mice and in the context of therapy-induced senescence (TIS). Resistance to immunotherapy is associated with a decrease in the accumulation and activation of CD8 T cells within tumors. Elimination of senescent cells restores immune homeostasis within the tumor...
Damien Maggiorani

Metabolic regulation of skeletal cell fate and function

3 weeks 5 days ago
Bone development and bone remodelling during adult life are highly anabolic processes requiring an adequate supply of oxygen and nutrients. Bone-forming osteoblasts and bone-resorbing osteoclasts interact closely to preserve bone mass and architecture and are often located close to blood vessels. Chondrocytes within the developing growth plate ensure that bone lengthening occurs before puberty, but these cells function in an avascular environment. With ageing, numerous bone marrow adipocytes...
Steve Stegen

Stem cell secretome treatment improves whole-body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice

3 weeks 5 days ago
Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral...
Zachary J Fennel

Intermittent fasting and longevity: From animal models to implication for humans

3 weeks 6 days ago
In recent years, intermittent fasting (IF) and its numerous modifications have been increasingly suggested as a promising therapy for age-related problems and a non-pharmacological strategy to extend lifespan. Despite the great variability in feeding schedules that we describe in the current work, underlying physiological processes are the same and include a periodic switch from glucose metabolism (generated by glycogenolysis) to fatty acids and fatty acid-derived ketones. Many of the beneficial...
Olha Strilbytska

Worldwide cohort studies to support healthy ageing research: data availabilities and gaps

3 weeks 6 days ago
CONCLUSIONS: The comprehensive summary of data availability enables timely evidence to contribute to the United Nations Decades of Healthy Ageing goals of promoting healthy ageing for all. Highlighted gaps guide strategies for increased data collection in regions with limited cohort studies. Comprehensive data, encompassing intrinsic capacity and various sociodemographic, social, and environmental factors, is crucial for advancing our understanding of healthy ageing and its underlying pathways.
Saman Khalatbari-Soltani

MicroRNA-7 deficiency ameliorates d-galactose-induced aging in mice by regulating senescence of Kupffer cells

3 weeks 6 days ago
Aging is intricately linked to immune system dysfunction. Recent studies have highlighted the biological function of microRNA-7 (miR-7) as a novel regulator of immune cell function and related diseases. However, the potential role of miR-7 in aging remains unexplored. Here, we investigated the contribution of miR-7 to d-gal-induced aging in mice, focusing on its regulation of senescent Kupffer cells. Our findings revealed that miR-7 deficiency significantly ameliorated the aging process,...
Ya Wang

Senolytic therapeutics: An emerging treatment modality for osteoarthritis

4 weeks ago
Osteoarthritis (OA), a chronic joint disease affecting millions of people aged over 65 years, is the main musculoskeletal cause of diminished joint mobility in the elderly. It is characterized by lingering pain and increasing deterioration of articular cartilage. Aging and accumulation of senescent cells (SCs) in the joints are frequently associated with OA. Apoptosis resistance; irreversible cell cycle arrest; increased p16INK4a expression, secretion of senescence-associated secretory phenotype...
Md Meraj Ansari

Sonic hedgehog signalling pathway contributes in age-related disorders and Alzheimer's disease

4 weeks 1 day ago
Alzheimer's disease (AD) is caused by the aging process and manifested by cognitive deficits and progressive memory loss. During aging, several conditions, including hypertension, diabetes, and cholesterol, have been identified as potential causes of AD by affecting Sonic hedgehog (Shh) signalling. In addition to being essential for cell differentiation and proliferation, Shh signalling is involved in tissue repair and the prevention of neurodegeneration. Neurogenesis is dependent on Shh...
Arun Parashar

Improving geriatric outcomes through nutritional and immunonutritional strategies: Focus on surgical setting by a comprehensive evidence review

4 weeks 1 day ago
The aging population worldwide has led to an increased request for surgical interventions in older, geriatric, and frail patients. However, all the physiological changes related to aging are associated with many challenges in the perioperative period, strongly impacting surgical outcomes. Nutritional status plays a pivotal role in determining the resilience of older adults to surgical stress and their ability to recover postoperatively. It is well known that malnutrition, a prevalent concern in...
Virginia Boccardi

Understanding the intricacies of cellular senescence in atherosclerosis: Mechanisms and therapeutic implications

4 weeks 1 day ago
Cardiovascular disease is currently the largest cause of mortality and disability globally, surpassing communicable diseases, and atherosclerosis is the main contributor to this epidemic. Aging is intimately linked to atherosclerosis development and progression, however, the mechanism of aging in atherosclerosis is not well known. To emphasize the significant research on the involvement of senescent cells in atherosclerosis, we begin by outlining compelling evidence that indicates various types...
Ilyas Ali

A single-nuclei paired multiomic analysis of the human midbrain reveals age- and Parkinson's disease-associated glial changes

4 weeks 1 day ago
Age is the primary risk factor for Parkinson's disease (PD), but how aging changes the expression and regulatory landscape of the brain remains unclear. Here we present a single-nuclei multiomic study profiling shared gene expression and chromatin accessibility of young, aged and PD postmortem midbrain samples. Combined multiomic analysis along a pseudopathogenesis trajectory reveals that all glial cell types are affected by age, but microglia and oligodendrocytes are further altered in PD. We...
Levi Adams

Age-associated accumulation of B cells promotes macrophage inflammation and inhibits lipolysis in adipose tissue during sepsis

4 weeks 1 day ago
Non-canonical lipolysis induced by inflammatory cytokines or Toll-like receptor ligands is required for the regulation of inflammation during endotoxemia and sepsis. Canonical lipolysis induced by catecholamines declines during aging due to factors including an expansion of lymphocytes, pro-inflammatory macrophage polarization, and an increase in chronic low-grade inflammation; however, the extent to which the non-canonical pathway of lipolysis is active and impacted by immune cells during aging...
Anna Carey

Acetyl-CoA carboxylase obstructs CD8<sup>+</sup> T cell lipid utilization in the tumor microenvironment

4 weeks 2 days ago
The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor-infiltrating T cells (TILs), hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to...
Elizabeth G Hunt

Lung-function trajectories: relevance and implementation in clinical practice

4 weeks 2 days ago
Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course. As a result, a range of lung-function trajectories exist in the population. Below average trajectories are associated with respiratory, cardiovascular, metabolic, and mental health...
Erik Melén

Somatic mutations in human ageing: New insights from DNA sequencing and inherited mutations

4 weeks 2 days ago
The accumulation of somatic mutations is a driver of cancer and has long been associated with ageing. Due to limitations in quantifying mutation burden with age in non-cancerous tissues, the impact of somatic mutations in other ageing phenotypes is unclear. Recent advances in DNA sequencing technologies have allowed the large-scale quantification of somatic mutations in ageing tissues. These studies have revealed a gradual accumulation of mutations in normal tissues with age as well as a...
Kasit Chatsirisupachai
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