Longevity Research Research Articles

Pterostilbene Targets Hallmarks of Aging in the Gene Expression Landscape in Blood of Healthy Rats.

Polyphenols from the phytoestrogen group, including pterostilbene (PTS), are known for their antioxidant, anti-inflammatory, and anti-cancer effects. In recent reports, phytoestrogens attenuate age-related diseases; however, their pro-longevity effects in healthy models in mammals remain unknown. As longevity research demonstrates age-related transcriptomic signatures in human blood, the current study hypothesizes that phytoestrogen-supplemented diet may induce changes in gene expression that ultimately confer pro-longevity benefits. In the present study, RNA sequencing is conducted to determine transcriptome-wide changes in gene expression in whole blood of healthy rats consuming diets supplemented with phytoestrogens. Ortholog cell deconvolution is applied to analyze the omics data. The study discovered that PTS leads to changes in the gene expression landscape and PTS-target genes are associated with functions counteracting hallmarks of aging, including genomic instability, epigenetic alterations, compromised autophagy, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular interaction, and loss of proteostasis. These functions bridge together under anti-inflammatory effects through multiple pathways, including immunometabolism, where changes in cellular metabolism (e.g., ribosome biogenesis) impact the immune system. The findings provide a rationale for pre-clinical and clinical longevity studies and encourage investigations on PTS in maintaining cellular homeostasis, decelerating the process of aging, and improving conditions with chronic inflammation.

The missions of companies in the Henokiens Association: Content analyses of their configuration with linkages to business longevity

Rapidly changing business environments and fierce competition are making it increasingly difficult for modern companies to maintain competitive advantage and accomplish business longevity. This study can fill the research gap in mission research and longevity research, and provides implications on what form and content of mission should be selected when determining the direction of a company’s corporate strategy. Although a company’s mission is a communication tool that represents the company’s strategic priorities and unique values, it has rarely been considered an important factor in business longevity. This study conducts a content analysis of the mission statements of 43 companies in the Henokiens Association to clarify the linkage between a company’s mission and business longevity and the configurations of long-lived firms’ missions. Our results show most long-lived firms have clear missions and perceptions of familism expansion. The firms’ past, present, and future additions to their concern for products, business growth, unique philosophy, and stakeholders are highlighted in their mission statements. Therefore, the main theoretical contribution of focusing on the corporate mission as a factor of business longevity in this study is not only a new approach to the longevity factor, but also the discovery of new values of the mission in strategic management research. The practical contribution of this study is that it reveals that companies seeking long-term competitive advantage in the market need to design, possess, and share a high-quality mission from a long-term perspective and instill the ideology of extended familyism. It can also provide hints about strategic priorities for small, family-run businesses facing threats to their survival.

Modelling the age distribution of longevity leaders

Human longevity leaders with remarkably long lifespan play a crucial role in the advancement of longevity research. In this paper, we propose a stochastic model to describe the evolution of the age of the oldest person in the world by a Markov process, in which we assume that the births of the individuals follow a Poisson process with increasing intensity, lifespans of individuals are independent and can be characterized by a gamma–Gompertz distribution with time-dependent parameters. We utilize a dataset of the world’s oldest person title holders since 1955, and we compute the maximum likelihood estimate for the parameters iteratively by numerical integration. Based on our preliminary estimates, the model provides a good fit to the data and shows that the age of the oldest person alive increases over time in the future. The estimated parameters enable us to describe the distribution of the age of the record holder process at a future time point.

How maternal caring affects longevity

When it comes to longevity, everyone wants to live for eternity. Longevity research has often led scientists to dark alleys with several candidate molecules responsible for aging. Pioneering genetic studies on model organisms like Caenorhabditis elegans and Drosophila melanogaster discovered the most well-conserved longevity pathways, mainly caloric restriction and the insulin/insulin-like growth factor 1signaling pathways. Apart from these complex molecular circuitries that drive longevity, a recent study published by Zipple et al. (Proceedings of the National Academy of Sciences, 2024) showed that the relationship between mother and grandmother with the child may determine why some animals and humans live longer than expected for their size. Animals that spend more time with their mothers during early life end up living longer but with reduced capacity to produce offspring. This exciting piece of research has far more consequences than just these findings. It implies the importance of the mother in one’s life and the role of parental care in providing longevity and reproductive success.

The Longevity Med Summit: insights on healthspan from cell to society.

In recent years, there has been a paradigm shift with regards to ageing, challenging its traditional perception as an inevitable and natural process. Researchers have collectively identified hallmarks of ageing, nine of which were initially proposed in 2013 and expanded in 2023 to include disabled macroautophagy, chronic inflammation, and dysbiosis, enhancing our understanding of the ageing process at microscopic, cellular, and system-wide levels. Strategies to manipulate these hallmarks present opportunities for slowing, preventing, or reversing age-related diseases, thereby promoting longevity. The interdependence of these hallmarks underscores the necessity of a comprehensive, systems-based approach to address the complex processes contributing to ageing. As a primary risk factor for various diseases, ageing diminishes healthspan, leading to extended periods of compromised health and multiple age-related conditions towards the end of life. The significant gap between healthspan and lifespan holds substantial economic and societal implications. The inaugural Longevity Med Summit (4-5 May 2023, Cascais, Portugal) provided an international forum to discuss the academic and industry landscape of healthy longevity research, preventive medicine and clinical practice to enhance healthspan.

Longevity as a Responsibility: Constructing Healthy Aging by Enacting within Contexts over the Entire Lifespan.

Studying aging now requires going beyond the bio-psycho-social model and incorporating a broader multidisciplinary view capable of capturing the ultimate complexity of being human that is expressed as individuals age. Current demographic trends and the lengthening of life expectancies allow the observation of long-lived individuals in full health. These super-agers are no longer an exception. Indeed, individuals can have a good quality of life even over age 70 and living with chronic or neurodegenerative diseases. This change is driven in part by the cohort effect observed in people who are about to age today (e.g., better schooling, more advanced health conditions, and technologization) but more so by the gradual overcoming of ageist views. An aged person is no longer seen as a quitter but rather as one empowered to direct their own trajectory of potentially healthy longevity. According to this vision, this article proposes a situated lifespan perspective for the study of aging that integrates pedagogical models of developmental ecology with psychological theories of optimal experience to understand the individual motivational perspective on aging. At the same time, it does not disregard analyzing the daily and cultural contexts in which everyone situates and that guide aging trajectories. Nor does it forget that aging people are body-mind (embodied) organisms that, with contexts and through motivations, seize opportunities for action (affordances) to evolve in an optimal way during their lifespan. This theoretical reflection sheds new light on the aging process and on future trends in healthy longevity research.

Short lifespan is one's fate, long lifespan is one's achievement: lessons from Daphnia.

Studies of longevity rely on baseline life expectancy of reference genotypes measured in standardized conditions. Variation among labs, protocols, and genotypes makes longevity intervention studies difficult to compare. Furthermore, extending lifespan under suboptimal conditions or that of a short-lived genotype may be of a lesser theoretical and translational value than extending the maximal possible lifespan. Daphnia is becoming a model organism of choice for longevity research complementing data obtained on traditional models. In this study, we report longevity of several genotypes of a long-lived species D. magna under a variety of protocols, aiming to document the highest lifespan, factors reducing it, and parameters that change with age and correlate with longevity. Combining longevity data from 25 experiments across two labs, we report a strong intraspecific variation, moderate effects of group size and medium composition, and strong genotype-by-environment interactions with respect to food level. Specifically, short-lived genotypes show no caloric restriction (CR) effect, while long-lived ones expand their lifespan even further under CR. We find that the CR non-responsive clones show little correlation between longevity and two measures of lipid peroxidation. In contrast, the long-lived, CR-responsive clones show a positive correlation between longevity and lipid hydroperoxide abundance, and a negative correlation with MDA concentration. This indicates differences among genotypes in age-related accumulation and detoxification of LPO products and their effects on longevity. Our observations support the hypothesis that a long lifespan can be affected by CR and levels of oxidative damage, while genetically determined short lifespan remains short regardless.

RNA analysis of the longest living vertebrate Greenland shark revealed an abundance of LINE-like elements in its transcriptome

The Greenland shark (Somniosus microcephalus) is an enigmatic species known for its exceptional longevity and extraordinary adaptations to the cold environment. This animal lives in the arctic and subarctic regions of the North Atlantic Ocean. Surprisingly, even though it is a vertebrate with the longest known lifespan, its transcriptome has not been studied yet. Therefore, we isolated and analyzed RNA in the Greenland shark samples. Our findings reveal some important information about the possible genetic mechanisms that could contribute to its longevity. We identified a highly expressed long interspersed nuclear element-like transcript (LINE-like) that is supposed to be associated with extended lifespan and resilience to age-related diseases, possibly through an improved telomere maintenance mechanism. This research not only contributes to our understanding of the biology and evolution of the Greenland shark but could also have implications for human longevity research.

The hallmarks of aging as a conceptual framework for health and longevity research.

The inexorability of the aging process has sparked the curiosity of human beings since ancient times. However, despite this interest and the extraordinary scientific advances in the field, the complexity of the process has hampered its comprehension. In this context, The Hallmarks of Aging were defined in 2013 with the aim of establishing an organized, systematic and integrative view of this topic, which would serve as a conceptual framework for aging research. Ten years later and promoted by the progress in the area, an updated version included three new hallmarks while maintaining the original scope. The aim of this review is to determine to what extent The Hallmarks of Aging achieved the purpose that gave rise to them. For this aim, we have reviewed the literature citing any of the two versions of The Hallmarks of Aging and conclude that they have served as a conceptual framework not only for aging research but also for related areas of knowledge. Finally, this review discusses the new candidates to become part of the Hallmarks list, analyzing the evidence that supports whether they should or should not be incorporated.

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

AbstractThe revolution in aging research through the past decade has driven the progress in interventions that promote longevity. Dissection of the “old” hallmarks of aging has provided solid data for the definition of at least three “new” ones, opening avenues for the development of novel hallmark‐targeted pro‐longevity approaches. The quest for geroprotectors is of enormous interest with the ultimate goal of finding the alchemical stone that induces healthy aging and increases lifespan, pushing the limits of human longevity or even uncovering the absence of such limits. Several of the well‐appreciated geroprotectors that are recognized as longevity promoters are of natural origin such as metformin, resveratrol, aspirin, and spermidine. As the search for pharmacological modulators of healthspan and lifespan continues, numerous studies are focusing on the potential of plant secondary metabolites. The current review attempts to critically assess the available interventions and the breakthrough discoveries in the field of longevity research over the past decade. Correspondingly, novel approaches targeting the hallmarks of aging have been outlined, and the future goals in longevity research have been enlightened. Special emphasis has been placed on the potential of plant‐derived compounds as pro‐longevity agents.

Advancing longevity research through decentralized science.

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.

Myotis bat STING attenuates aging-related inflammation in female mice.

Bats, notable as the only flying mammals, serve as natural reservoir hosts for various highly pathogenic viruses in humans (e.g., SARS-CoV and Ebola virus). Furthermore, bats exhibit an unparalleled longevity among mammals relative to their size, particularly the Myotis bats, which can live up to 40 years. However, the mechanisms underlying these distinctive traits remain incompletely understood. In our prior research, we demonstrated that bats exhibit dampened STING-interferon activation, potentially conferring upon them the capacity to mitigate virus- or aging-induced inflammation. To substantiate this hypothesis, we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING ( MdSTING) into the mouse genome. We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process. Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice, as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines, immunopathology, and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo. These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner. Although the underlying mechanism awaits further study, this research has critical implications for bat longevity research, potentially contributing to our comprehension of healthy aging in humans.

Seed Longevity and Ageing: A Review on Physiological and Genetic Factors with an Emphasis on Hormonal Regulation.

Upon storage, seeds inevitably age and lose their viability over time, which determines their longevity. Longevity correlates with successful seed germination and enhancing this trait is of fundamental importance for long-term seed storage (germplasm conservation) and crop improvement. Seed longevity is governed by a complex interplay between genetic factors and environmental conditions experienced during seed development and after-ripening that will shape seed physiology. Several factors have been associated with seed ageing such as oxidative stress responses, DNA repair enzymes, and composition of seed layers. Phytohormones, mainly abscisic acid, auxins, and gibberellins, have also emerged as prominent endogenous regulators of seed longevity, and their study has provided new regulators of longevity. Gaining a thorough understanding of how hormonal signalling genes and pathways are integrated with downstream mechanisms related to seed longevity is essential for formulating strategies aimed at preserving seed quality and viability. A relevant aspect related to research in seed longevity is the existence of significant differences between results depending on the seed equilibrium relative humidity conditions used to study seed ageing. Hence, this review delves into the genetic, environmental and experimental factors affecting seed ageing and longevity, with a particular focus on their hormonal regulation. We also provide gene network models underlying hormone signalling aimed to help visualize their integration into seed longevity and ageing. We believe that the format used to present the information bolsters its value as a resource to support seed longevity research for seed conservation and crop improvement.

HALL: a comprehensive database for human aging and longevity studies.

Diverse individuals age at different rates and display variable susceptibilities to tissue aging, functional decline and aging-related diseases. Centenarians, exemplifying extreme longevity, serve as models for healthy aging. The field of human aging and longevity research is rapidly advancing, garnering significant attention and accumulating substantial data in recent years. Omics technologies, encompassing phenomics, genomics, transcriptomics, proteomics, metabolomics and microbiomics, have provided multidimensional insights and revolutionized cohort-based investigations into human aging and longevity. Accumulated data, covering diverse cells, tissues and cohorts across the lifespan necessitates the establishment of an open and integrated database. Addressing this, we established the Human Aging and Longevity Landscape (HALL), a comprehensive multi-omics repository encompassing a diverse spectrum of human cohorts, spanning from youngadults to centenarians. The core objective of HALL is to foster healthy aging by offering an extensive repository of information on biomarkers that gauge the trajectory of human aging. Moreover, the database facilitates the development of diagnostic tools for aging-related conditions and empowers targeted interventions to enhance longevity. HALL is publicly available at https://ngdc.cncb.ac.cn/hall/index.

AgeAnnoMO: a knowledgebase of multi-omics annotation for animal aging.

Aging entails gradual functional decline influenced by interconnected factors. Multiple hallmarks proposed as common and conserved underlying denominators of aging on the molecular, cellular and systemic levels across multiple species. Thus, understanding the function of aging hallmarks and their relationships across species can facilitate the translation of anti-aging drug development from model organisms to humans. Here, we built AgeAnnoMO (https://relab.xidian.edu.cn/AgeAnnoMO/#/), a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8596 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes multiple aging regulators across species via multi-omics data, comprehensively annotating aging-related genes, proteins, metabolites, mitochondrial genes, microbiotas and age-specific TCR and BCR sequences tied to aging hallmarks for these species and tissues. AgeAnnoMO not only facilitates a deeper and more generalizable understanding of aging mechanisms, but also provides potential insights of the specificity across tissues and species in aging process, which is important to develop the effective anti-aging interventions for diverse populations. We anticipate that AgeAnnoMO will provide a valuable resource for comprehending and integrating the conserved driving hallmarks in aging biology and identifying the targetable biomarkers for aging research.

The role of cardiac resident macrophage in cardiac aging.

Advancements in longevity research have provided insights into the impact of cardiac aging on the structural and functional aspects of the heart. Notable changes include the gradual remodeling of the myocardium, the occurrence of left ventricular hypertrophy, and the decline in both systolic and diastolic functions. Macrophages, a type of immune cell, play a pivotal role in innate immunity by serving as vigilant agents against pathogens, facilitating wound healing, and orchestrating the development of targeted acquired immune responses. Distinct subsets of macrophages are present within the cardiac tissue and demonstrate varied functions in response to myocardial injury. The differentiation of cardiac macrophages according to their developmental origin has proven to be a valuable strategy in identifying reparative macrophage populations, which originate from embryonic cells and reside within the tissue, as well as inflammatory macrophages, which are derived from monocytes and recruited to the heart. These subsets of macrophages possess unique characteristics and perform distinct functions. This review aims to summarize the current understanding of the roles and phenotypes of cardiac macrophages in various conditions, including the steady state, aging, and other pathological conditions. Additionally, it will highlight areas that require further investigation to expand our knowledge in this field.

Reductionism and Holism in the History of Aging and Longevity Research: Does the Whole Have Parts? Part 2. The Upwelling of Holism

Reductionism and Holism in the History of Aging and Longevity Research: Does the Whole Have Parts? Part 2. The Upwelling of Holism

Funding Life-Extension Research.

While the worldwide trend in life expectancy continues to increase slightly overall, the trend for the last few decades in developed countries is that more people are spending more years in poor health with multiple chronic comorbidities. These chronic conditions in aging populations consume high proportions of national healthcare budgets. The relatively young field of longevity research, after accumulating insights into the mechanisms of aging and producing dramatic laboratory demonstrations of life extension in some organisms, is entering the translational phase. This phase, through clinical trials, will confirm or refute the "geroscience hypothesis" that drugs can change the trajectory of the processes of aging within cells, and ultimately in living humans. At the same time, traditional funding patterns do not favor such visionary "moonshot" research, which, despite the potential for ultimately providing benefits for everyone, offers little prospect for rapid return on investment and high probabilities for early phase failure. New radical funding strategies incentivizing innovation will have to be called into play.

Towards AI-driven longevity research: An overview.

While in the past technology has mostly been utilized to store information about the structural configuration of proteins and molecules for research and medical purposes, Artificial Intelligence is nowadays able to learn from the existing data how to predict and model properties and interactions, revealing important knowledge about complex biological processes, such as aging. Modern technologies, moreover, can rely on a broader set of information, including those derived from the next-generation sequencing (e.g., proteomics, lipidomics, and other omics), to understand the interactions between human body and the external environment. This is especially relevant as external factors have been shown to have a key role in aging. As the field of computational systems biology keeps improving and new biomarkers of aging are being developed, artificial intelligence promises to become a major ally of aging research.

DNA methylation states in supercentenarians

Molecular mechanisms contributing to healthy ageing and longevity are not yet completely understood.1 One potential mechanism involved is DNA methylation,1 a process that serves as a dynamic regulator of cell function and can also be a means to define epigenetic age, an indicator of biological age.1,2 Studying the epigenetic patterns of supercentenarians has special relevance in longevity research because epigenetics is the connection between the environment and the inherited genome.1