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Renal αKlotho along with fibroblast growth factor 23 regulates phosphate and vitamin D metabolism. Its cleavage yields soluble Klotho controlling intracellular processes. αKlotho has anti-inflammatory and antioxidant effects and is nephro- and cardioprotective. AMP-dependent kinase (AMPK) is a nephro- and cardioprotective energy sensor. Given that both αKlotho and AMPK have beneficial effects in similar organs, we studied whether AMPK regulates αKlotho gene expression in Madin-Darby canine kidney, normal rat kidney 52E, and human kidney 2 cells. Using quantitative real-time PCR and western blotting, we measured αKlotho expression upon pharmacological manipulation or siRNA-mediated knockdown of AMPKα. AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) enhanced αKlotho expression, an effect reduced in the presence of AMPK inhibitor compound C or siRNA targeting AMPK catalytic α-subunits (α1 and α2). Similarly, AMPK activators metformin and phenformin upregulated αKlotho transcripts. Taken together, our results suggest that AMPK is a powerful inducer of αKlotho and could thereby contribute to the development of future therapeutic interventions.
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BACKGROUND: Proteostasis is a critical aging hallmark responsible for removing damaged or misfolded proteins and their aggregates by improving proteasomal degradation through the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS). Research on the impact of heat-killed probiotic bacteria and their structural components on aging hallmarks and innate immune responses is scarce, yet enhancing these effects could potentially delay age-related diseases. RESULTS: This study introduces a novel heat-killed Levilactobacillus brevis strain MKAK9 (HK MKAK9), along with its exopolysaccharide (EPS), demonstrating their ability to extend longevity by improving proteostasis and immune responses in wild-type Caenorhabditis elegans. We elucidate the underlying mechanisms through a comprehensive approach involving mRNA- and small RNA sequencing, proteomic analysis, lifespan assays on loss-of-function mutants, and quantitative RT-PCR. Mechanistically, HK MKAK9 and its EPS resulted in downregulation of the insulin-like signaling pathway in a DAF-16-dependent manner, enhancing protein ubiquitination and subsequent proteasomal degradation through activation of the ALP pathway, which is partially mediated by microRNA mir-243. Importantly, autophagosomes engulf ubiquitinylated proteins, as evidenced by increased expression of the autophagy receptor sqst-3, and subsequently fuse with lysosomes, facilitated by increased levels of the lysosome-associated membrane protein (LAMP) lmp-1, suggesting the formation of autolysosomes for degradation of the selected cargo. Moreover, HK MKAK9 and its EPS activated the p38 MAPK pathway and its downstream SKN-1 transcription factor, which are known to regulate genes involved in innate immune response (thn-1, ilys-1, cnc-2, spp-9, spp-21, clec-47, and clec-266) and antioxidation (sod-3 and gst-44), thereby reducing the accumulation of reactive oxygen species (ROS) at both cellular and mitochondrial levels. Notably, SOD-3 emerged as a transcriptional target of both DAF-16 and SKN-1 transcription factors. CONCLUSION: Our research sets a benchmark for future investigations by demonstrating that heat-killed probiotic and its specific cellular component, EPS, can downregulate the insulin-signaling pathway, potentially improving the autophagy-lysosome pathway (ALP) for degrading ubiquitinylated proteins and promoting organismal longevity. Additionally, we discovered that increased expression of microRNA mir-243 regulates insulin-like signaling and its downstream ALP pathway. Our findings also indicate that postbiotic treatment may bolster antioxidative and innate immune responses, offering a promising avenue for interventions in aging-related diseases.
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BACKGROUND: There have been mixed results reported internationally when associating vegetarian dietary patterns with all-cause and cause-specific mortalities. OBJECTIVE: To extend our previous results by evaluating, with a larger number of deaths (N=12515), cause-specific mortalities comparing different vegetarian types to non-vegetarians. METHODS: This prospective study used data from the Adventist Health Study-2 cohort. Mortality was ascertained between study baseline, 2002-2007 and follow-up through 2015. Dietary data were collected at baseline using a validated quantitative food frequency questionnaire and then categorized into five dietary patterns: non-vegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo-vegetarian, and vegan. Main outcomes and measures include all-cause and cause-specific mortalities using Cox proportional hazards regression models and competing risk methods. RESULTS: The analytic sample included 88400 participants who provided 971424 person-years of follow-up. We report results as estimated at ages 65 and 85 years due to age-dependence of many hazard ratios (HR's). Compared to non-vegetarians, vegetarians had lower risks of mortality (HR's and 95% confidence interval - 95% CI at age 65; followed by same at age 85 years in parentheses), overall (0.89[0.83,0.95];0.98[0.91,1.04]), from renal failure (0.52[0.38,0.70]; 0.65[0.55,0.76]), infectious disease (0.57[0.40,0.82];0.90[0.70,1.17]), diabetes (0.51[0.33,0.78]; 0.69[0.53,0.88]), select cardiac (0.75[0.65,0.87]; 0.89[0.83,0.95]), and ischemic heart disease causes (0.730.59,0.90]; 0.84[0.75,0.94]). Vegans, lacto-ovo-vegetarians and pesco-vegetarians were also observed to have lower risks of total mortality and several similar cause-specific mortalities. However, higher cause-specified neurological mortalities were observed among older vegetarians (estimated at age 85 years), specifically stroke (HR=1.17[1.02,1.33]), dementia (HR=1.13[1.00,1.27]), and Parkinson's Disease (HR=1.37[0.98,1.91]). Results in Black subjects for vegetarian/nonvegetarian comparisons largely followed the same trends, but HR's were less precise due to smaller numbers. CONCLUSIONS: Vegetarian diets are associated with lower risk for all-cause and many cause-specific mortalities, especially among males and in younger subjects. However, higher risks were observed among older vegetarians for stroke and dementia. These results need further support and investigation.
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Recent progress on the underlying biological mechanisms of healthy longevity has propelled the field from elucidating genetic modification of healthy longevity hallmarks to defining mechanisms of gut microbiota influencing it. Importantly, the role of gut microbiota in the healthy longevity of the host may provide unprecedented opportunities to decipher the plasticity of lifespan on a natural evolutionary scale and shed light on using microbiota-targeted strategies to promote healthy aging and combat age-related diseases. This review investigates how gut microbiota affects healthy longevity, focusing on the mechanisms through which gut microbiota modulates it. Specifically, we focused on the ability of gut microbiota to enhance the intestinal barrier integrity, provide protection from inflammaging, ameliorate nutrientsensing pathways, optimize mitochondrial function, and improve defense against age-related diseases, thus participating in enhancing longevity and healthspan.
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BACKGROUND: This study compared the mortality risk of long-lived siblings with the U.S. population average and their spouse controls, and investigated the leading causes of death and the familial effect in death pattern. METHODS: In the Long Life Family Study (LLFS), 1,264 proband siblings (Mean age 90.1, SD 6.4) and 172 spouses (83.8, 7.2) from 511 U.S.-based families were recruited and followed over 12 years. Their survival function was compared with a birth cohort-, baseline age-, sex-, and race-matched pseudo sample from U.S. census data. To examine underlying and contributing causes, we examined in detail 338 deaths with complete death adjudication at the University of Pittsburgh Field Center through the year 2018. A familial effect on survival and death pattern was examined using mixed effect models. RESULTS: The LLFS siblings had better survival than the matched U.S. population average. They also had slightly but not significantly better survival than their spouses' (HR=1.18 [95%CI 0.94-1.49]) after adjusting for age and sex. Age at death ranged from 75-104 years, mean 91.4. The leading causes of death were cardiovascular disease (33.1%), dementia (22.2%), and cancer (10.7%). Mixed effect model shows a significant random effect of family in survival, with adjustment of baseline age and sex. There was no significant familial effect in the underlying cause of death or conditions directly contributing to death among siblings recruited by the University of Pittsburgh Field Center. CONCLUSION: Our findings demonstrate a higher survival in the LLFS siblings than the U.S. census data, with a familial component of survival. We did not find significant correspondence in causes of death between siblings within families.
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Kombucha, a beverage traditionally obtained through the fermentation of tea, is believed to have beneficial health properties. Therefore, characterizing the microorganisms responsible for this fermentation is essential to demonstrate its potential health benefits and to identify candidates for new probiotics. In this study, four probiotic yeast strains isolated from kombucha tea were identified, by the PCR-RFLP analysis of the ribosomal ITS region and the sequence of the D1/D2 domain of the 26S rDNA, as Brettanomyces bruxellensis (UVI55 and UVI56) and B. anomalus (UVI57 and UVI58). Properties relevant to probiotics were also studied in these strains. All of them showed excellent survival in simulated gastric (99%-100%) and duodenal (95%-100%) juices. The ability to self-aggregate (38%-100%), adhesion to xylene (15%-50%) and, above all, adhesion to Caco-2 cells (4%-21%), revealed its potential capacity to adhere to the intestinal epithelium. In addition, the tested strains showed excellent antioxidant capacity (82%-94%), antimicrobial activity against different pathogens (Escherichia coli, Staphylococcus aureus, Salmonella enterica, Listeria monocytogenes, and Bacillus cereus), as well as remarkable cytotoxic activity against colon, melanoma and ovarian tumor cell lines. Finally, using Caenorhabditis elegans as a model, strain UVI56 exhibited ability to both extend the lifespan of the nematode and protect it against infection by S. enterica. These results support the probiotic and functional properties of the analyzed strains. In conclusion, the study revealed that kombucha tea could be a source of potential probiotics that contribute to its health-promoting properties and that the characterized Brettanomyces strains could be exploited directly as probiotics or for the development of new functional foods.
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The study of longevity and its determinants has been revitalized with the rise of microbiome scholarship. The gut microbiota have been established to play essential protective, metabolic, and physiological roles in human health and disease. The gut dysbiosis has been identified as an important factor contributing to the development of multiple diseases. Accordingly, it is reasonable to hypothesize that the gut microbiota of long-living individuals have healthy antiaging-associated gut microbes, which, by extension, might provide specific molecular targets for antiaging treatments and interventions. In the present study, we compared the gut microbiota of Chinese individuals in two different age groups, long-living adults (aged over 90 years) and elderly adults (aged 65-74 years) who were free of major diseases. We found significantly lower relative abundances of bacteria in the genera Sutterella and Megamonas in the long-living individuals. Furthermore, we established that while biological processes such as autophagy (GO:0006914) and telomere maintenance through semiconservative replication (GO:0032201) were enhanced in the long-living group, response to lipopolysaccharide (GO:0032496), nicotinamide adenine dinucleotide oxidation (GO:0006116), and S-adenosyl methionine metabolism (GO:0046500) were weakened. Moreover, the two groups were found to differ with respect to amino acid metabolism. We suggest that these compositional and functional differences in the gut microbiota may potentially be associated with mechanisms that contribute to determining longevity or aging.
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This review explores the role and health impacts of probiotics, focusing specifically on Bifidobacterium spp. It highlights the functionalities that Bifidobacteria can provide, underscored by the historical evolution of definitions and technological advancements related to probiotics. By examining the association between Bifidobacteria and longevity, this review suggests new avenues for health enhancement. Highlighting case studies of centenarians, it presents examples related to human aging, illuminating the potential links to longevity through research on Bifidobacterium strains found in centenarians. This review not only emphasizes the importance of current research but also advocates for further investigation into the health benefits of Bifidobacteria, underlining the necessity for continuous study in the nutraceutical field.
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Background: Digital transformation in rural areas has become a key policy priority worldwide. China is also implementing a digital village strategy and actively promoting the digital transformation of rural governance to improve the well-being of rural residents. The literature suggests that digital governance is linked to health, but the mechanisms behind this relationship remain unclear. Methods: Using data from the 2021 China Land Economic Survey (CLES), this paper examines the impact of digital governance on the health, longevity, and mental health of rural residents. To enhance the robustness of the conclusions, this paper also introduces a dual machine learning model to solve the endogeneity problem of the model. Conclusion and discussion: This study concludes that digital governance has a significant positive impact on the health of rural residents. This finding remains consistent even after addressing endogeneity issues and conducting numerous robustness tests. Mechanistic analyses indicate that digital governance can enhance rural residents' health by improving village governance (environmental governance) and increasing the efficiency of access to personal information. Further analysis reveals that digital governance significantly increases the life expectancy of rural residents but that its effect on mental health is not significant. This study provides new insights into how digital governance affects health, with important implications for health policy development.
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População Rural , Humanos , China , Saúde Mental , Inquéritos e Questionários , Feminino , MasculinoRESUMO
BACKGROUND: Use of permanent hair dyes causes unintended oxidative damage during the short time frame of the dyeing process that leads to perceivable changes in the feel, manageability and appearance of hair. Moreover, after hair has been dyed, regular exposure to the sun as a key environmental stressor continues to stimulate additional oxidative damage and to induce newly developed hair colours to fade prematurely or undergo changes in colour quality. OBJECTIVE: To document the utility of acetyl zingerone methyl ether (MAZ) as a newly designed haircare ingredient to afford extra protection against oxidative damage and safeguard the integrity of hair colour. RESULTS: We demonstrate that MAZ is compatible chemically with the high alkaline conditions required for the colouring process and from theoretical calculations preferentially binds Fe and Cu ions relative to Ca or Zn ions. In model Fenton reactions MAZ effectively chelated active redox metals (Fe and Cu ions) in the presence of excess Ca+2 ions to inhibit the production of hydroxyl radicals, and in separate studies, MAZ neutralized singlet oxygen with greater efficiency than α-tocopherol by a factor of 2.5. When mixed into permanent dyes prior to hair tress application, MAZ significantly reduced combing forces, and SEM images led to substantial reductions in visual signs of surface damage. In a 28-day clinical study, relative to controls, mixing MAZ into hair dyes prior to application interfered neither with colour development nor with ability to cover grey hair and led to significant improvements in perceived attributes associated with hair's condition immediately following the dyeing process. Over a 28-day maintenance phase, especially between Day 14 and Day 28, continued use of shampoo and conditioner containing MAZ significantly preserved gloss measurements and hair colour in terms of longevity and colour quality as remaining desired and fresh compared to use of control shampoo and conditioner. CONCLUSION: This work establishes MAZ as a next-generation hair care ingredient for use in permanent dyes to attenuate oxidative damage and in shampoos and conditioners to promote longevity of hair colour and to maintain overall health and appearance of hair on a daily basis.
CONTEXTE: L'utilisation de colorants capillaires permanents provoque des dommages oxydatifs involontaires pendant la courte période du processus de teinture, ce qui entraîne des changements perceptibles dans la texture, la maniabilité et l'aspect des cheveux. De plus, après la teinture des cheveux, une exposition régulière au soleil comme facteur de stress environnemental clé continue de stimuler des dommages oxydatifs supplémentaires et d'induire une décoloration prématurée des nouvelles couleurs de cheveux ou des changements dans la qualité de la couleur. OBJECTIF: Documenter l'utilité de l'éther méthylique d'acétyl zingérone (MAZ) en tant qu'ingrédient de soin capillaire nouvellement conçu pour offrir une protection supplémentaire contre les dommages oxydatifs et sauvegarder l'intégrité de la couleur des cheveux. RÉSULTATS: Nous démontrons que le MAZ est chimiquement compatible avec les conditions alcalines élevées requises pour le processus de coloration et, d'après les calculs théoriques, lie de préférence les ions Fe et Cu aux ions Ca ou Zn. Dans les réactions de Fenton, le MAZ chélate efficacement les métaux redox actifs (atomes de Fe et de Cu) en présence d'un excès d'ions Ca+2 pour inhiber la production de radicaux hydroxyles et, dans des études séparées, le MAZ neutralise l'oxygène seul avec une efficacité supérieure à celle de l'αtocophérol, d'un facteur de 2.5. Lorsqu'il est mélangé à des teintures permanentes avant l'application de la coiffure, le MAZ réduit de manière significative les forces de peignage et, d'après les images SEM, conduit à des réductions substantielles des signes visuels de dommages à la surface. Dans une étude clinique de 28 jours, le mélange de MAZ dans les teintures capillaires avant l'application n'interfère pas avec le développement de la couleur ni avec la capacité à couvrir les cheveux gris et conduit à des améliorations significatives des attributs perçus associés à l'état des cheveux immédiatement après le processus de teinture. Au cours d'une phase d'entretien de 28 jours, en particulier entre le 14ème et le 28ème jour, l'utilisation continue du shampooing et de l'aprèsshampooing contenant du MAZ a permis de préserver de manière significative les mesures de brillance et la couleur des cheveux en termes de longévité et de qualité de la couleur, qui reste telle que désirée et nette, par rapport à l'utilisation du shampooing et de l'aprèsshampooing de contrôle. CONCLUSION: Ces travaux font du MAZ un ingrédient de nouvelle génération pour les soins capillaires, à utiliser dans les teintures permanentes pour atténuer les dommages oxydatifs et dans les shampooings, et aprèsshampooings pour promouvoir la longévité de la couleur des cheveux et maintenir la santé et l'apparence générales des cheveux au quotidien.
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Although it is well established that a vegetable-rich (Mediterranean) diet is associated with health benefits in later life, the mechanisms and biological origins of this benefit are not well established. This review seeks to identify the components a healthful diet that reduce the individual's suffering from non-communicable disease and extend longevity. We note the difference between the claims made for an essential diet (that prevents deficiency syndromes) and those argued for a diet that also prevents or delays non-communicable diseases and ask: what chemicals in our food induce this added resilience, which is effective against cardiovascular and neurodegenerative diseases, diabetes and even cancer? Working in the framework of acquired resilience (tissue resilience induced by a range of stresses), we arguethat the toxins evolved by plants as part of allelopathy (the competition between plant species) are key in making the 'healthful difference'. We further suggest the recognition of a category of micronutrients additional to the established 'micro' categories of vitamins and trace elements and suggest also that the new category be called 'trace toxins'. Implications of these suggestions are discussed.
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There are two major subtypes of adipose tissue, i.e., white adipose tissue (WAT) and brown adipose tissue (BAT). It has been known for a long time that WAT mediates obesity and impairs healthful longevity. More recently, interest has focused on BAT, which, unlike WAT, actually augments healthful aging. The goal of this review is to examine the role of BAT in mediating healthful longevity. A major role for BAT and its related beige adipose tissue is thermogenesis, as a mechanism to maintain body temperature by producing heat through uncoupling protein 1 (UCP1) or through UCP1-independent thermogenic pathways. Our hypothesis is that healthful longevity is, in part, mediated by BAT. BAT protects against the major causes of impaired healthful longevity, i.e., obesity, diabetes, cardiovascular disorders, cancer, Alzheimer's disease, reduced exercise tolerance, and impaired blood flow. Several genetically engineered mouse models have shown that BAT enhances healthful aging and that their BAT is more potent than wild-type (WT) BAT. For example, when BAT, which increases longevity and exercise performance in mice with disruption of the regulator of G protein signaling 14 (RGS14), is transplanted to WT mice, their exercise capacity is enhanced at 3 days after BAT transplantation, whereas BAT transplantation from WT to WT mice also resulted in increased exercise performance, but only at 8 weeks after transplantation. In view of the ability of BAT to mediate healthful longevity, it is likely that a pharmaceutical analog of BAT will become a novel therapeutic modality.
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In an era marked by scientific stagnation, Decentralized Science (DeSci) challenges the inefficiencies of traditional funding and publishing systems. DeSci employs blockchain technology to address the misalignment of incentives in academic research, emphasizing transparency, rapid funding, and open-source principles. Centralized institutions have been linked to a deceleration of progress, which is acutely felt in the field of longevity science-a critical discipline as aging is the #1 risk factor for most diseases. DeSci proposes a transformative model where decentralized autonomous organizations (DAOs) facilitate community-driven funding, promoting high-risk, high-reward research. DeSci, particularly within longevity research, could catalyze a paradigm shift towards an equitable, efficient, and progressive scientific future.
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The social service approach for the elderly that emerged in the USSR in the late 1980s and was introduced within the framework of a federal law in 1995 was oriented towards care and service provision. However, various authors have noted that the needs of the elderly and the availability of services often do not coincide, and this gap is growing with the change of generations of the elderly. The modern approach, the founder of which was the Polish demographer E.Rosset, reflected in a number of international documents, prioritizes supporting employment and maintaining independence for the elderly for as long as possible. However, there is still little research clarifying the specific services needed by the elderly themselves. The aim of this article is to demonstrate that the needs and capabilities of the «older generation¼ are changing noticeably, and the existing approach to the provision of social services, which largely took shape in the 1990s, is outdated. Our research question is: do the digital ecosystems (services) being developed by the Information and Analytical Center of St. Petersburg Government correspond to the needs of the elderly on the one hand, and the provisions enshrined in the Madrid Plan on the other? The study employed qualitative methods: an analysis of a pilot survey of users of the «Active Longevity¼ service and the opinions of participants in a focus group (age of informants 60-75 years) of elderly individuals conducted on 16.03.2024.
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Serviço Social , Humanos , Idoso , Serviço Social/organização & administração , Federação Russa , Masculino , Feminino , Necessidades e Demandas de Serviços de Saúde , Serviços de Saúde para Idosos/organização & administração , Serviços de Saúde para Idosos/tendências , Avaliação das Necessidades , Pessoa de Meia-Idade , Grupos Focais , Idoso de 80 Anos ou maisRESUMO
There is a growing interest in social behavior change with age,1,2,3,4,5 and the impacts of sociality on longevity,6,7,8 but current knowledge is broadly limited to primates, societies structured by dominance hierarchies, or single-sex studies. It is less clear how social aging patterns emerge in carnivores. The African lion (Panthera leo), a species that lives in egalitarian fission-fusion societies, presents an exceptional opportunity to examine social aging. Across felids, lions are unique in their dependence on conspecifics for many essential processes,9,10,11 and there is vast knowledge of lion behavioral ecology,10,11,12,13,14 including documented reproductive senescence in both sexes.14,15 Applying spatial-social network analyses across 30 years of data on the wild Serengeti lion population, we show that sex strongly modulates patterns of social aging and longevity. Group size increased with age for both sexes, but only males experienced significant changes in associate numbers (degree), specifically to females, which peaked in mid-life before declining. While aging females experienced declines in intra-sex connectivity (strength) and bond strength (mean strength), they peaked in both to males during mid-life. Male inter-sex strength also peaked in mid-life, while conversely their intra-sex strength and mean strength significantly dipped in mid-life. Although social associations were important for survival in both sexes, the investment diverged significantly: females' overall network connectivity was key for longevity, while the number of associates was important for males. These findings illustrate important potential effects of social aging in a wild carnivore and demonstrate how these diverge strongly between the sexes.
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Background: Previous researched has demonstrated potent health and survival advantages across three-generations in longevity-enriched families. However, the survival advantage associated with familial longevity may manifest earlier in life than previously thought. Methods: We conducted a matched cohort study comparing early health trajectories in third-generation grandchildren (n = 5,637) and fourth-generation great-grandchildren (n = 14,908) of longevity-enriched sibships to demographically matched births (n = 41,090) in Denmark between 1973 and 2018. Results: Lower risk was observed across a range of adverse early life outcomes in the grandchildren, including infant mortality (Hazard Ratio (HR) = 0.53, 95% CI [0.36, 0.77]), preterm birth (Odds Ratio (OR) = 0.82, [0.72, 0.93]), small for gestational age (OR = 0.83, [0.76, 0.90]) and neonatal respiratory disorders (OR = 0.77, [0.67, 0.88]). Relative advantages in parental education and maternal smoking were observed in both generations to a similar degree. However, a much smaller reduction in infant mortality was observed in the great-grandchildren (HR = 0.90, [0.70, 1.17]) and benefits across other outcomes were also less consistent, despite persisting socioeconomic and behavioural advantages. Lastly, maternal, and paternal lines of transmission were equipotent in the transmission of infant survival advantages. Conclusions: Descendants of longevity-enriched sibships exhibit a broad health advantage manifesting as early the perinatal period. However, this effect is strongly diluted over successive generations. Our findings suggest that exceptional health and survival may have early developmental components and implicate heritable genetic and or epigenetic factors in their specific transmission.
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This study aimed to provide a comprehensive picture of the life expectancy of dogs in Portugal, focusing on the impact of diverse factors including breed, sex, size, and skull shape. The final dataset, gathering data from the national registry database, consisted of 278,116 dogs with confirmed deaths. The mean lifespan at birth for all the dogs was around 8.91 years, with the female dogs tended to have a similar lifespan to male dogs. The analysis of life expectancy at birth for the 20 most common non-Portuguese breeds and 10 Portuguese breeds revealed that Yorkshire Terriers had the highest life expectancy (10.89 years) and French Bulldogs the lowest (6.27 years). Size and cephalic index were found to be influential factors, with large brachycephalic breeds exhibiting shorter life expectancies and smaller, mesocephalic breeds experiencing longer lifespans. Additionally, the cephalic index had a more substantial impact on life expectancy compared to body size. These findings enhance the understanding of the factors influencing canine longevity and aid in developing strategies to improve the health and lifespan of companion dogs.
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Geroscience posits that molecular drivers underlie the aging process. Gerotherapeutics entail strategies to counter molecular drivers of aging to reduce the chronic diseases and geriatric syndromes they trigger. Although the concept of gerotherapeutics for prevention has generated much excitement, the implications of prescribing potentially harmful medications to older adults who are "healthy" have been associated with many delays. Concerns regarding safety and valid endpoints have contributed to holdups. In contrast, it has been relatively easier to implement trials of medications with gerotherapeutic properties as novel approaches to remedy disease. In these applications, the risks of the medications are easier to justify when therapeutic benefits are perceived as outweighing the harms of the disease. Likewise, metrics of effective disease treatments are often seen as more reliable and quantifiable than metrics of health prolongation. Overall, clarifying geroscience mechanisms in disease therapeutic applications provides key opportunities to advance translational geroscience, especially as preventive geroscience trials are often encumbered. In this review, gerotherapeutic benefits of canakinumab, cholchicine, and zoledronic acid as parts of disease management are considered. Longevity Clinics and other opportunities to advance translational geroscience as parts of contemporary care are also discussed.
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Envelhecimento , Pesquisa Translacional Biomédica , Humanos , Envelhecimento/fisiologia , Idoso , Gerociência , Geriatria/métodosRESUMO
Given the unprecedented rate of global aging, advancing aging research and drug discovery to support healthy and productive longevity is a pressing socioeconomic need. Holistic models of human and population aging that account for biomedical background, environmental context, and lifestyle choices are fundamental to address these needs, but integration of diverse data sources and large data sets into comprehensive models is challenging using traditional approaches. Recent advances in artificial intelligence and machine learning, and specifically multimodal transformer-based neural networks, have enabled the development of highly capable systems that can generalize across multiple data types. As such, multimodal transformers can generate systemic models of aging that can predict health status and disease risks, identify drivers, or breaks of physiological aging, and aid in target discovery against age-related disease. The unprecedented capacity of transformers to extract and integrate information from large and diverse data modalities, combined with the ever-increasing availability of biological and medical data, has the potential to revolutionize healthcare, promoting healthy longevity and mitigating the societal and economic impacts of global aging.
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Envelhecimento , Descoberta de Drogas , Humanos , Envelhecimento/fisiologia , Descoberta de Drogas/métodos , Inteligência Artificial , Longevidade/efeitos dos fármacos , Aprendizado de Máquina , Redes Neurais de ComputaçãoRESUMO
The human lifespan is influenced by various factors, with physical activity being a significant contributor. Despite the clear benefit of exercise on health and longevity, the association between different types of sports and lifespan is yet to be considered. Accordingly, we aimed to study this association in a large international cohort of former athletes using a robust linear regression model. We collected data on athletes from public sources, accumulating a total of 95,210 observations, 95.5% of which were accounted for by males. The dataset represented athletes born between 1862 and 2002 from 183 countries across 44 sports disciplines. We calculated the change in lifespan by measuring the difference in age between athletes and the corresponding reference populations, while accounting for variations caused by sex, year of death, and country. The results revealed that various sports impacted lifespan differently, with male athletes being more likely to experience benefits from sports than female athletes. Among male athletes, pole vaulting and gymnastics were linked to the highest extension in lifespan (8.4 years, 95% CI [6.8, 9.9] and 8.2 years, 95% CI [7.4, 9], respectively), while volleyball and sumo wrestling were the most negatively associated with lifespan (- 5.4 years, 95% CI [- 7, - 3.8]; - 9.8 years, 95% CI [- 11, - 8.6], respectively). The association between lifespan and popular team sports in males was positive for cricket, rowing, baseball, water polo, Australian rules, hurling, lacrosse, field hockey, minimal for rugby, canoeing and kayaking, basketball, gridiron football, and football (soccer), and negative for handball and volleyball. Racquet sports (i.e., tennis and badminton) exhibited a consistent and positive association in both male and female athletes, as shown by an extended lifespan of up to 5.7 years in males (95% CI [5, 6.5]) and 2.8 years in females (95% CI [1.8, 3.9]). Although lacking conclusive evidence, we theorize that the observed results may be attributed to the aerobic and anaerobic characteristics of each sport, with mixed sports yielding the maximum benefits for the lifespan. While results from female athletes should be cautiously interpreted, our study highlights the complex interplay between sports and lifespan and contributes to the growing body of knowledge on the multifaceted relationship between physical activity and human longevity.