Biogerontology最新文献

Heat-induced hormesis in longevity is the increase in life span resulting from the previous exposure to a mild heat stress early in life. Here we examined heat-induced hormesis of Drosophila buzzatii in five mass-mating populations, which were derived from five wild populations along an elevation gradient from 202 to 1855 m above sea level in North-Western Argentina. Five day old flies were exposed to 37.5 °C for 90 min to induce hormesis and its possible variation across altitudinal populations. This heat treatment strongly extended longevity in lowland-derived flies from the most heat-resistant population only. Both heat-induced effects on longevity and heat-knockdown time (heat-stress sensitivity) were negatively correlated to altitude of population of origin. Hormesis was positively correlated to heat-knockdown time across populations. These results indicate that variation in heat-induced hormesis can not be considered as independent of heat-stress sensitivity (or heat-knockdown time) in populations of insects.

The Argonaute family genes (piwi and aub) involved in the production of small RNAs are responsible for the regulation of many cellular processes, including the suppression of genome instability, modulation of gene activity, and transposable elements. Dysfunction of these genes and the associated activation of transposable elements adversely affect reproductive development and quality of life. The role of transposons in contrast to retrotransposons and their interaction with genes of the Argonaute family in aging processes have not been studied. This study considers a scenario in which the piwi and aub genes in the presence of functional hobo transposons can modify the effects from the level of DNA damage to lifespan. The simultaneous presence of mutation (piwi or aub) and hobo (regardless of size) in the genome has practically no effect or (less often) leads to a decrease in the level of DNA damage in ovarian cells. A high level of sterility and low ovarian reserve were noted mainly with a combination of mutations and full-sized hobo elements. The combination of these two genetic factors negatively affects the fertility of young females and embryonic survival. Isolated cases of restoration of reproductive functions with age were noted but only in females that had low fertility in the early period of life. The presence of hobo transposons contributed to an increase in the lifespan of both mutant and non-mutant females. Dysfunction of the piwi and aub genes (without hobo) can reduce the lifespan of both sexes. Together, each mutation and hobo transposons act antagonistically/additively (in females) and synergistically/antagonistically (in males) to change the lifespan. In parameters of locus-specific instability, hobo activation was more pronounced in piwi gene dysfunction. The results obtained complement data on the study of new functions of Argonaute family genes and their interactions with transposable elements in the aging process.

Brain aging is a major risk factor for cognitive diseases such as Alzheimer's disease (AD) and vascular dementia. The rate of aging and age-related pathology are modulated by stress responses and repair pathways that gradually decline with age. However, recent reports indicate that exceptional longevity sustains and may even enhance the stress response. Whether normal and exceptional aging result in either attenuated or enhanced stress responses across all organs is unknown. This question arises from our understanding that biological age differs from chronological age and evidence that the rate of aging varies between organs. Thus, stress responses may differ between organs and depend upon regenerative capacity and ability to manage damaged proteins and proteotoxicity. To answer these questions, we assessed age-dependent changes in brain stress responses with normally aged wild type and long-lived Dwarf mice. Results from this study show that normal aging unfavorably impacts activation of the brain heat shock (HS) axis with key changes noted in the transcription factor, HSF1, and its regulation. Exceptional aging appears to preserve and strengthen many elements of HSF1 activation in the brain. These results support the possibility that reconstitution of aging brain stress responses requires a multi-factorial approach that addresses HSF1 protein levels, its DNA binding, and regulatory elements such as phosphorylation and protein interactions.

Frailty syndrome denotes a decreased capacity of the body to maintain the homeostasis and stress of the internal environment, which simultaneously increases the risk of adverse health outcomes in older adults, including disability, hospitalization, falls, and death. To promote healthy aging, we should find strategies to cope with frailty. However, the pathogenesis of frailty syndrome is not yet clear. Recent studies have shown that the diversity, composition, and metabolites of gut microbiota significantly changed in older adults with frailty. In addition, several frailty symptoms were alleviated by adjusting gut microbiota with prebiotics, probiotics, and symbiosis. Therefore, we attempt to explore the pathogenesis of frailty syndrome in older people from gut microbiota and summarize the existing interventions for frailty syndrome targeting gut microbiota, with the aim of providing timely and necessary interventions and assistance for older adults with frailty.

About a year ago, members of the editorial board of Biogerontology were requested to respond to a query by the editor-in-chief of the journal as to what one question within their field of ageing research still needs to be asked and answered. This editorial is inspired by the wide range and variety of questions, ideas, comments and suggestions received in response to that query. The seven knowledge gaps identified in this article are arranged into three main categories: evolutionary aspects of longevity, biological survival and death aspects, and heterogeneity in the progression and phenotype of ageing. This is not an exhaustive and exclusive list, and may be modified and expanded. Implications of these knowledge gaps, especially in the context of ongoing attempts to develop effective interventions in ageing and longevity are also discussed.

Plasma proteins serve as biomarkers of aging and various age-related diseases. While a number of plasma proteins have been identified that increase or decrease with age, the interpretation of each protein is challenging. This is due to the nature of plasma, which is a mixture of factors secreted by many different tissues and cells. Therefore, the catalog of age-related proteins secreted by a single cell type in a single tissue would be useful for understanding tissue-specific aging patterns. In this study, the author addressed this challenge by integrative data mining of the Human Protein Atlas and the recently published result of large-scale aging proteomics research. Finally, we identified the 17 age-related proteins produced by a single tissue and a single cell type: MBL2 and HP in the liver (hepatocytes), SFTPC in the lung (type II alveolar cells), PRL and POMC in the pituitary (anterior cells), GCG, CUZD1 and CPA2 in the pancreas (pancreatic cells), MYBPC1 in skeletal muscle (myocytes), PTH in the parathyroid gland (glandular cells), LPO and AMY1A in the salivary gland (glandular cells), INSL3 in the male testis (Leydig cells), KLK3 and KLK4 in the male prostate (glandular cells), MPO and ACP5 in immune cells. This list of proteins would be potentially useful for understanding age-related changes in the plasma proteome and inter-tissue networks.

FOXO3 is a member of the FOXO transcription factor family and is known for regulating cellular survival in response to stress caused by various external and biological stimuli. FOXO3 decides cell fate by modulating cellular senescence, apoptosis and autophagy by transcriptional regulation of genes involved in DNA damage response and oxidative stress resistance. These cellular processes are tightly regulated physiologically, with FOXO3 acting as the hub that integrates signalling networks controlling them. The activity of FOXO3 is influenced by post-translational modifications, altering its subcellular localisation. In addition, FOXO3 can also be regulated directly or indirectly by microRNAs (miRNAs) or vice versa. This review discusses the involvement of various miRNAs in FOXO3-driven cellular responses such as senescence, apoptosis, autophagy, redox and inflammation defence. Given that these responses are linked and influence cell fate, a thorough understanding of the complex regulation by miRNAs would provide key information for developing therapeutic strategy and avoid unintended consequences caused by off-site targeting of FOXO3.

Sestrins are a type of highly conserved stress-inducing protein that has antioxidant and mTORC1 inhibitory functions. Metabolic dysfunction and aging are the main risk factors for development of human diseases, such as diabetes, neurodegenerative diseases, and cancer. Sestrins have important roles in regulating glucose and lipid metabolism, anti-tumor functions, and aging by inhibiting the reactive oxygen species and mechanistic target of rapamycin complex 1 pathways. In this review, the structure and biological functions of sestrins are summarized, and how sestrins are activated and contribute to regulation of the downstream signal pathways of metabolic and aging-related diseases are discussed in detail with the goal of providing new ideas and therapeutic targets for the treatment of related diseases.

With the increase of population aging, the prevalence of type 2 diabetes (T2D) is also rising. Aging affects the tissues and organs of the whole body, which is the result of various physiological and pathological processes. Adipose tissue has a high degree of plasticity and changes with aging. Aging changes the distribution of adipose tissue, affects adipogenesis, browning characteristics, inflammatory status and adipokine secretion, and increases lipotoxicity. These age-dependent changes in adipose tissue are an important cause of insulin resistance and T2D. Understanding adipose tissue changes can help promote healthy aging process. This review summarizes changes in adipose tissue ascribable to aging, with a focus on the role of aging adipose tissue in insulin resistance and T2D.

Cellular senescence is characteristic of the development and progression of multiple age-associated diseases. Accumulation of senescent cells in the heart contributes to various age-related pathologies. Several compounds called senolytics have been designed to eliminate these cells within the tissues. In recent years, the use and study of senolytics increased, representing a promising field for finding accessible and safe therapies for cardiovascular disease (CVD) treatment. This mini-review discusses the changes in the aging heart and the participation of senescent cells in CVD, as well as the use of senolytics to prevent the progression of myocardial damage, mainly the effect of dasatinib and quercetin. In particular, the mechanisms and physiological effects of senolytics therapies in the aged heart are discussed.