Aging & Longevity

Metformin is the most commonly prescribed glucose-lowering agent worldwide for the treatment of type II diabetes. Due to evidence of improvements in healthspan and lifespan in model organisms, and mechanistic data relevant to the hallmarks of aging, it has been considered a promising candidate in the search for pharmacological interventions that may attenuate the ageing process in humans. Various epidemiological studies have been influential in generating support for this hypothesis. These...

COVID-19 mortality disproportionately affects the elderly, yet the cellular and molecular factors contributing to age-related immune system remodeling remain unclear. Using SARS-CoV-derived ssRNA sequences, we modeled age-dependent immune responses in mice. Aged mice exhibited higher mortality and severe lung inflammation upon viral ssRNA challenge, mirroring clinical observations. We uncovered a pre-existing inflammatory state in aged mice, characterized by elevated baseline levels of specific...

Influenza poses a significant threat to older adults, exacerbated by age-related immune decline and the high prevalence of chronic conditions. Despite being the most effective preventive measure, influenza vaccination rates among this population remain alarmingly low, with Italy and Europe failing to meet the World Health Organization’s target of 75% coverage for individuals aged 65 and over. This review, informed by a geriatric conference in Enna, Sicily, examines the epidemiology of influenza...

Lifespan is a highly variable life trait across the Tree of Life, governed by complex and multifactorial mechanisms. While some conserved pathways regulating longevity have been identified in various species, the molecular basis of this phenotype is far from being understood. In this context, the adoption of new model species and methods of investigation may offer opportunities to explore the molecular underpinnings of longevity in animals. In this study, we investigated the genomic resources of...

CONCLUSIONS: Those aged > 70, at risk of malnutrition, and having dementia had higher odds of sarcopenia. In contrast, having an educational level of a diploma or lower, ≥ one session of physical activity per week, and having hypertension showed a reverse association with sarcopenia. Findings underscore the importance of targeted interventions to mitigate sarcopenia risk in aging populations.

Advanced age is one of the most recognizable risk factors for dry eye. Dry eye disease affects millions worldwide and can result from age-related lacrimal gland dysfunction, which correlates with a decline in lacrimal gland secretory cell function and chronic inflammation. This study investigated the potential of calorie restriction to maintain lacrimal gland and ocular surface health. Adult female C57BL/6 J mice were subjected to a 40% calorie restriction for 4 months, starting at 6-7 months...

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Cytochrome b(5) reductase 3 (CYB5R3) overexpression mimics several metabolic benefits of calorie restriction, with sex- and tissue-specific effects. This study aimed to investigate how CYB5R3 overexpression impacts hepatic metabolism in young mice, focusing on mitochondrial biogenesis, lipid metabolism, autophagy and nutrient sensing pathways thus establishing a baseline that allows for subsequent comparisons with older animals. The accrual of CYB5R3 polypeptide exhibited marked sexual...

CONCLUSIONS: Working and non-working older adults showed similar biological circadian rhythms, but working ones had a more robust rest-activity rhythm and higher levels and intensity of physical activity.

A previous study employing fMRI measures of retrieval-related neural selectivity reported that young, but not older, adults employ 'retrieval gating' to attenuate aspects of an episodic memory that are irrelevant to the retrieval goal. We examined whether the weak memories of the older adults in that study rendered goal-irrelevant memories insufficiently intrusive to motivate retrieval gating. Young and older participants studied words superimposed on rural or urban scenes, or on scrambled...

Aging is considered as an independent risk factor for cardiovascular diseases. Common hallmarks of vascular aging include endothelial dysfunction, vascular inflammation, elevated oxidative stress, and telomere dysfunction. Perivascular adipose tissue (PVAT) is the local aggregate of adipose tissue surrounding the vascular bed, serving as a critical regulator of vascular function via either paracrine or endocrine manners. Aging-dependent malfunction of adipose tissues increases the risk of...

The development of a multicellular organism is a highly intricate process tightly regulated by numerous genes and pathways in both spatial and temporal manners. Here, we present Flysta3D-v2, a comprehensive multi-omics atlas of the model organism Drosophila spanning its developmental lifespan from embryo to pupa. Our datasets encompass 3D single-cell spatial transcriptomic, single-cell transcriptomic, and single-cell chromatin accessibility information. Through the integration of multimodal...

Pancreatic β-cells are essential for maintaining glucose homeostasis throughout life. Although rodent models have been instrumental in elucidating β-cell biology, notable differences exist between rodents and humans across fetal, postnatal and adult stages. This review provides a comparative analysis of β-cell development, proliferation and regenerative capacity between these two species, highlighting critical divergences that must be considered when translating preclinical findings to human...

Heteroplasmic pathogenic mitochondrial DNA (mtDNA) mutations are key drivers of mitochondrial diseases, yet their tissue-specific and cell-specific accumulation patterns during aging and the mechanistic links to pathology remain poorly understood. In this study, we employed DddA-derived cytosine base editor technology to generate three mouse models harboring distinct pathogenic mitochondrial tRNA mutations. These mutations exhibited age-dependent accumulation in the kidneys, leading to severe...

Muscle atrophy around joints is a common issue for people with osteoarthritis (OA), but its causes are poorly understood. Here we demonstrate that chronic inflammation in quadriceps muscle coincides with OA in mice, characterized by an increase in macrophages, activation of inflammatory pathways and tissue vascularization. We show that, during OA progression, macrophages progressively exhibit increasing phenotypes of senescence and promote muscle atrophy through paracrine induction of...

RNA engineering has yielded a new class of medicines but faces limitations depending on RNA size and function. Here we demonstrate the synthesis and enzymatic stabilization of telomerase RNA component (TERC), a therapeutically relevant long non-coding RNA (lncRNA) that extends telomere length and replicative lifespan in human stem cells. Compared with therapeutic mRNAs, engineered TERC RNA (eTERC) depends on avoiding nucleoside base modifications and incorporates a distinct trimethylguanosine 5'...

Diabetes has long-term, potentially severe implications for healthspan and lifespan and imposes an immense burden on global healthcare, the economy and society. Although a repertoire of medications is available to treat diabetes, these do not properly address the eventual lack of functional pancreatic beta cells that are needed to secrete insulin and maintain glucose homeostasis. Human islet cell transplantation from deceased donors is an established treatment for insulin-requiring type 1...

Cholesterol metabolism disorders have been shown to correlate with multiple physiopathologic aspects of cellular aging. However, whether indicators reflecting cholesterol metabolism [e.g., remnant cholesterol (RC)] can serve as biomarkers for biological aging remains unclear. To address this gap, this study aimed to explore the relationship between RC and phenotypic age acceleration (PhenoAgeAccel) using data from the National Health and Nutrition Examination Survey (NHANES) database. First,...

Ageing is associated with declines in neuromuscular function, yet the neural mechanisms underlying strength adaptations in older adults remain unclear. While the corticospinal tract (CST) is the primary pathway for voluntary movement, the reticulospinal tract (RST) may play a compensatory role with age. This study investigated CST and RST responses following a single session of high-intensity metronome-paced strength training (MPST) in young and older adults. Thirty-five participants (17 young,...

With aging, deviation of human blood counts from their normal range accompanies the transition from health to disease. Hematopoietic stem and progenitor cells (HSPCs) deliver life-long multi-lineage output, but their variation across healthy humans with aging, and their diagnostic utility, haven't been characterized in depth thus far. To address this, we introduced an HSPC reference model using single-cell RNA profiling of circulating CD34^(+) HSPCs from 148 healthy age- and sex-diverse...