Biogerontology最新文献

The integumentary system serves as a crucial protective barrier and is subject to complex signaling pathways that regulate its physiological functions. As the body's first line of defense, the skin is continuously exposed to environmental stressors, necessitating a robust network of signaling molecules to maintain homeostasis. Considering the main cellular components to be keratinocytes, melanocytes, fibroblasts, and fibrous components, collagen of various types, this review explores the intricate signaling mechanisms that govern skin integrity, focusing on key pathways involved in impacts of ageing and environment factors on skin health. The role of growth factors, cytokines, hormones and other molecular mediators in these processes is examined. Specially for women, decrease of estrogen is determinant to alter signaling and to compromise skin structure, especially the dermis. Environmental factors, such as ultraviolet rays and pollution alongside the impact of ageing on signaling pathways, especially TGF-β and proteases (metalloproteinases and cathepsins). Furthermore, with advancing age, the skin's capacity to shelter microbiome challenges diminishes, leading to alterations in signal transduction and subsequent functional decline. Understanding these age-related changes is essential for developing targeted therapies aimed at enhancing skin health and resilience, but also offers a promising avenue for the treatment of skin disorders and the promotion of healthy ageing.

The early-life gut microbiota (GM) is increasingly recognized for its contributions to human health and disease over time. Microbiota composition, influenced by factors like race, geography, lifestyle, and individual differences, is subject to change. The GM serves dual roles, defending against pathogens and shaping the host immune system. Disruptions in microbial composition can lead to immune dysregulation, impacting defense mechanisms. Additionally, GM aids digestion, releasing nutrients and influencing physiological systems like the liver, brain, and endocrine system through microbial metabolites. Dysbiosis disrupts intestinal homeostasis, contributing to age-related diseases. Recent studies are elucidating the bacterial species that characterize a healthy microbiota, defining what constitutes a 'healthy' colonic microbiota. The present review article focuses on the importance of microbiome composition for the development of homeostasis and the roles of GM during aging and the age-related diseases caused by the alteration in gut microbial communities. This article might also help the readers to find treatments targeting GM for the prevention of various diseases linked to it effectively.

Despite frequent claims regarding radical extensions of human lifespan in the near future, many pragmatic scientists caution against excessive and baseless optimism on this front. In this study, we examine the compensation effect of mortality (CEM) as a potential challenge to substantial lifespan extension. The CEM is an empirical mortality regularity, often depicted as relative mortality convergence at advanced ages. Analysis of mortality data from 44 human populations, available in the Human Mortality Database, demonstrated that CEM can be represented as a continuous decline in relative mortality variation (assessed through the coefficient of variation and the standard deviation of the logarithm of mortality) with age, reaching a minimum corresponding to the species-specific lifespan. Through this method, the species-specific lifespan is determined to be 96-97 years, closely aligning with estimates derived from correlations between Gompertz parameters (95-98 years). Importantly, this representation of CEM can be achieved non-parametrically, eliminating the need for estimating Gompertz parameters. CEM is a challenge to lifespan extension, because it suggests that the true aging rate in humans (based on loss of vital elements, e.g., functional cells) remains stable at approximately 1% per year in the majority of human populations and is not affected by environmental or familial longevity factors. Given this rate of functional cell loss, one might anticipate that the total pool of functional cells could be entirely depleted by the age of 115-120 years creating physiological limit to human lifespan. Mortality pattern of supercentenarians (110 + years) aligns with this prediction.

The accumulation of pro-inflammatory senescent cells within tissues is a common hallmark of the aging process and many age-related diseases. This modification has been called the senescence-associated secretory phenotype (SASP) and observed in cultured cells and in cells isolated from aged tissues. Currently, there is a debate whether the accumulation of senescent cells within tissues should be attributed to increased generation of senescent cells or to a defect in their elimination from aging tissues. Emerging studies have revealed that senescent cells display an increased expression of several inhibitory immune checkpoint ligands, especially those of the programmed cell death protein-1 (PD-1) ligand-1 (PD-L1) proteins. It is known that the PD-L1 ligands, especially those of cancer cells, target the PD-1 receptor of cytotoxic CD8⁺ T and natural killer (NK) cells disturbing their functions, e.g., evoking a decline in their cytotoxic activity and promoting their exhaustion and even apoptosis. An increase in the level of the PD-L1 protein in senescent cells was able to suppress their immune surveillance and inhibit their elimination by cytotoxic CD8⁺ T and NK cells. Senescent cells are known to express ligands for several inhibitory immune checkpoint receptors, i.e., PD-1, LILRB4, NKG2A, TIM-3, and SIRPα receptors. Here, I will briefly describe those pathways and examine whether these inhibitory checkpoints could be involved in the immune evasion of senescent cells with aging and age-related diseases. It seems plausible that an enhanced inhibitory checkpoint signaling can prevent the elimination of senescent cells from tissues and thus promote the aging process.

Peritoneal immune cell function is a reliable indicator of aging and longevity in mice and inflammaging is associated with a shorter lifespan. Nevertheless, it is unknown if the content of cytokines in these immune cells is linked to individual differences in lifespan. Therefore, this work aimed to investigate different peritoneal leukocyte populations and their content in intracellular pro-inflammatory (TNF and IL-6) and anti-inflammatory (IL-10) cytokines by flow cytometry in adult (10 months-old, n = 8) and old (18 months-old, n = 20) female Swiss/ICR mice. In addition, old mice were monitored longitudinally throughout their aging process, and the same markers were analyzed at the very old (24 months-old, n = 8) and long-lived (30 months-old, n = 4) ages. The longitudinal follow-up allowed us to relate the investigated parameters to individual lifespans. The results show that long-lived female mice exhibit an adult-like profile in most parameters investigated but also display specific immune adaptations, such as increased CD4+ and CD8+ T cells containing the pro-inflammatory TNF cytokine and CD4+ T cells and macrophages containing the anti-inflammatory cytokine IL-10. These adaptations may underlie their exceptional longevity. In addition, a negative correlation was obtained between the percentage of cytotoxic T cells, KLRG-1/CD4, large peritoneal macrophages, and the percentage of CD4+ T cells containing IL-6 and macrophages containing IL-10 in old age and lifespan, whereas a positive correlation was found between the CD4/CD8 ratio and the longevity of the animals at the same age. These results highlight the crucial role of peritoneal leukocytes in inflammaging and longevity.

The aging process demonstrates notable differences between males and females, which are key factors in disease susceptibility and lifespan. The differences in sex chromosomes are fundamental to the presence of sex bias in organisms. Moreover, sex-specific epigenetic modifications and changes in sex hormone levels impact the development of immunity differently during embryonic development and beyond. Mitochondria, telomeres, homeodynamic space, and intestinal flora are intricately connected to sex differences in aging. These elements can have diverse effects on men and women, resulting in unique biological transformations and health outcomes as they grow older. This review explores how sex interacts with these elements and shapes the aging process.

Aging is defined as a progressive decline in physiological integrity, leading to impaired biological function, including fertility, and rising vulnerability to death. Disorders of DNA replication often lead to replication stress and are identified as factors influencing the aging rate. In this study, we aimed to reveal how the cells that lost strict control of the formation of crucial for replication initiation a pre-initiation complex impact the cells' physiology and aging. As strains with the lower pre-IC control (lowPICC) we used, Saccharomyces cerevisiae heterozygous strains having only one functional copy of genes, encoding essential replication proteins such as Cdc6, Dbf4, Sld3, Sld7, Sld2, and Mcm10. The lowPICC strains exhibited a significant reduction in the respective genes' mRNA levels, causing cell cycle aberrations and doubling time extensions. Additionally, the reduced expression of the lowPICC genes led to an aberrant DNA damage response, affected cellular and mitochondrial DNA content, extended the lifespan of post-mitotic cells, and increased the yeast's reproductive potential. Importantly, we also demonstrated a strong negative correlation between the content of cellular macromolecules (RNA, proteins, lipids, polysaccharides) and aging. The data presented here will likely contribute to the future development of therapies for treating various human diseases.

With the declining birth rates and aging societies in developed countries, the average age of the working population is increasing. Older people tend to get tired more easily, so prevention of fatigue is important to improve the quality of life for older workers. This study aimed to assess the mechanism of fatigue in older people, especially focused on relation between dysfunction of erythrocyte and fatigue. Total power (TP), which is the value of autonomic nerve activity, was measured as a value of fatigue and significantly decreased in workers with aging. As properties of senescent erythrocytes, the erythrocyte sedimentation rate and damaged erythrocytes population increased with aging and correlated with TP. These results suggested that the accumulation of damaged erythrocytes contributes to fatigue. Recent studies revealed that senescence-associated secretory phenotype (SASP), a phenomenon in which senescent cells secrete a variety of cytokines, affected hematopoiesis in bone marrow. We analyzed the effects of SASP factors on erythropoiesis and found that Interleukin -1α (IL-1α) suppressed erythrocyte differentiation of hematopoietic stem cells in vitro. We also showed that IL-1α levels in human blood and saliva increase with aging, suggesting the possibility that IL-1α level in saliva can be used to predict the decline in hematopoietic function.

Many biological mechanisms of aging well converge with radiation's biological effects. We used scientific insights from the field of aging to establish a novel hypoxic-hypercapnic environment (HHE) concept for radioprotection. According to this concept, HHE which possesses an anti-aging and longevity-promoting potential, should also act as a radiomitigator and radioprotector. As such, it might contribute greatly to the safety and wellbeing of individuals exposed to high levels of radiation, whether in planned events (e.g. astronauts) or in unplanned events (e.g. first responders in nuclear accidents).

Aging, a natural biological process, presents challenges in maintaining physiological well-being and is associated with increased vulnerability to diseases. Addressing aging mechanisms is crucial for developing effective preventive and therapeutic strategies against age-related ailments. Rosmarinus officinalis L. is a medicinal herb widely used in traditional medicine, containing diverse bioactive compounds that have been studied for their antioxidant and anti-inflammatory properties, which are associated with potential health benefits. Using network pharmacology, this study investigates the anti-aging function and underlying mechanisms of R. officinalis. Through network pharmacology analysis, the top 10 hub genes were identified, including TNF, CTNNB1, JUN, MTOR, SIRT1, and others associated with the anti-aging effects. This analysis revealed a comprehensive network of interactions, providing a holistic perspective on the multi-target mechanism underlying Rosemary's anti-aging properties. GO and KEGG pathway enrichment analysis revealed the relevant biological processes, molecular functions, and cellular components involved in treating aging-related conditions. KEGG pathway analysis shows that anti-aging targets of R. officinalis involved endocrine resistance, pathways in cancer, and relaxin signaling pathways, among others, indicating multifaceted mechanisms. Genes like MAPK1, MMP9, and JUN emerged as significant players. These findings enhance our understanding of R. officinalis's potential in mitigating aging-related disorders through multi-target effects on various biological processes and pathways. Such approaches may reduce the risk of failure in single-target and symptom-based drug discovery and therapy.