Aging & Longevity

Transcriptome analysis has become increasingly utilized in aging research. However, the identification of the key molecular changes underlying aging processes and longevity-promoting regimens from transcriptome data remains challenging. Here, we present Transcriptomic CLassification via Adaptive learning of Signature States (T-CLASS), an online tool that identifies, from transcriptome data, gene sets of several hundred genes that provide an optimal representation of longevity and aging...

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Global warming can postpone the autumn date of foliar senescence (DFS). Nevertheless, warming-associated droughts may induce earlier DFS. However, pre-season drought thresholds triggering an earlier DFS (PDT-DFS) are not clearly established. Using site-level DFS data since 1951, satellite-derived DFS data for 1982‒2021, and drought indices, we construct a copula-based Bayesian framework to identify the PDT-DFS over the Northern Hemisphere (>30°N). A higher probability of droughts is associated...

CONCLUSIONS: Reduced HGS and the presence of dynapenia were significantly associated with lower HRQoL, particularly among women. These findings highlight the critical role of muscle strength in maintaining the well-being of aging populations. Further longitudinal studies are warranted to validate these associations and elucidate potential causal mechanisms.

CONCLUSIONS: Caregiver burden is a multidimensional construct with significant implications for caregiver well-being. Key predictors of reduced well-being include self-perceived burden, multifaceted strain, and a diminished sense of life satisfaction. Gender differences were notable, with women reporting higher levels of strain and role overload. These findings underscore the need for comprehensive and gender-sensitive support strategies. Addressing social, financial, physical, and psychological...

Perturbations to the immune system influence organismal aging, yet identifying effective therapeutic targets that mitigate aging-related tissue decline or the pathogenesis of aging-related diseases, such as cancer, remains challenging. In this Perspective, we focus on the dysfunction and loss of resident tissue macrophages (RTMs) with aging of certain tissues, which promote local inflammation, compromise tissue health and contribute to tumorigenesis. The abnormal genesis of RTMs from the bone...

The classical role of adaptive immunity as a protector against external threats has expanded to include its functions in cancer surveillance, tissue repair and regeneration, and, more recently, it has emerged as a regulator of the aging process. In this Perspective, we discuss the mechanisms by which the deterioration of adaptive immunity contributes to inflammaging, cellular senescence and age-associated pathologies. We propose that age-related changes in lymphocytes contribute to aging through...

Immune responses underlying autoimmune diseases follow the same principles that protect individuals from infection and malignancies. However, while protective immunity wanes with progressive age, the risk for autoimmune disease steadily increases; incidence rates for many autoimmune diseases peak in later life. Here, we discuss whether aging predisposes to autoimmunity, arguing that disease progression in the autoimmune vasculitis giant cell arteritis is driven by age-inappropriate sustenance of...

Senescent cells are intrinsically immunogenic and can be eliminated by the immune system to facilitate tissue repair and regeneration. However, immune-mediated elimination is compromised with age, causing senescent cell accumulation in tissues, thus limiting healthspan and lifespan and promoting age-related diseases such as cancer. Here, we review how different components of the innate and adaptive immune systems, including natural killer cells, macrophages, neutrophils, dendritic cells, T cells...

All biological activities require energy through the intake and generation of metabolites. After reproductive age, altered metabolism, together with cellular and molecular perturbations in the immune system, are linked to organismal functional decline. Unresolved chronic inflammation originating from innate immune cells and loss of naive T cells with restriction of T cell receptor repertoire diversity emanating from age-related thymic involution are some of the mechanisms that limit healthspan...

Cellular aging of the immune system, commonly referred to as 'immunosenescence', drives a substantial decline in vaccine efficacy among older adults, who are already typically at a higher risk of reduced infection control. Therefore, preventive medicine requires novel strategies to improve vaccination in older adults, particularly by finding ways to mitigate immunosenescence and chronic inflammation. Here, we review how technical innovations, such as increased antigen amounts, improved adjuvants...

Inflammaging describes a chronic, systemic, low-grade inflammatory state that is recognized as a major risk factor for age-related diseases (ARDs) and a pivotal convergence point of multiple biological mechanisms involved in aging. Here, we discuss the heterogeneity of inflammaging, proposing that it emerges as a consequence of each individual's lifelong exposures to inflammatory stimuli, shaped by a unique combination of genetics, lifestyle, socioeconomic conditions and environmental factors...

Resilience-the ability to recover and maintain function following stresses-is a critical factor influencing treatment tolerance and recovery in older adults with cancer. Despite the high incidence of gynecologic cancers in postmenopausal individuals, resilience in this population remains underexplored, even though patients commonly face compounded stress from both chemotherapy and surgery. The goal of our research is (1) to test the feasibility of cognitive and physical function assessments in...

Male infertility remains a major unmet medical challenge, with poorly defined molecular mechanisms and no effective therapies. Here, we identify a stress granule-mediated necroptotic pathway as a key driver of non-obstructive azoospermia, a severe form of male infertility marked by the loss of spermatogenesis. Environmental or physiological stress activates eIF2α kinases, inducing stress granule formation and the recruitment of ZBP1 and RIPK3 into a cytoplasmic complex. This assembly triggers...

Protein aggregation is a hallmark of neurodegenerative diseases and is also observed in the brains of elderly individuals without such conditions, suggesting that aging drives the accumulation of protein aggregates. However, the comprehensive understanding of age-dependent protein aggregates involved in brain aging remains unclear. Here, we investigated proteins that become sarkosyl-insoluble with age and identified hyaluronan and proteoglycan link protein 2 (HAPLN2), a hyaluronic acid-binding...

The aging population worldwide necessitates the development of novel therapeutics that enhance the quality of life by preventing and treating age-related diseases. In this review, we first discuss the advantages of a dual-purpose target identification strategy for aging and age-related diseases, with assessment of the hallmarks of aging as an approach to identify such dual-purpose targets. Resulting from a convergence of aging research with machine learning (ML) and other artificial intelligence...

Late-onset depression (LOD) is closely linked to Alzheimer's disease (AD), marked by shared biological pathways and common risk factors. The neurobiological alterations associated with depression, particularly the dysregulation of amyloid-β (Aβ), play a critical role in the acceleration of disease progression. In individuals suffering from LOD, Aβ peptides - specifically Aβ40 and Aβ42 - exhibit distinct profiles in plasma, cerebrospinal fluid (CSF), and brain tissue, highlighting the substantial...

Aging is a series of adverse changes over time that increases mortality risk. Several hypotheses have been proposed to explain aging, including Leslie Orgel's Error-Catastrophe Theory, which asserts that translation errors erode the translational machinery, become self-amplifying, and eventually lead to death. Evidence for the theory is scarce, especially regarding intra-specific fidelity-longevity correlations. Here, we demonstrate that the correlation can be hidden by the constrained evolution...

The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues from 24 organ donors aged 20-75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal...

Calorie restriction (CR) improves health and longevity. CR induces a periodic fasting cycle in mammals; our study compares CR with unanticipated fasting (F), when the food is unexpectedly withheld. F induces hepatic steatosis, whereas CR reduces it; surprisingly, the difference is not due to hepatic β-oxidation. Liver transcriptome analysis identifies fatty acid transporters (Slc27a1 and Slc27a2), triglyceride (TAG) synthesis (Gpat4), and lipid storage (Plin2 and Cidec) genes to be upregulated...