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JACC. Cardiovascular Imaging May 2024Population aging is one of the most important demographic transformations of our time. Increasing the "health span"-the proportion of life spent in good health-is a... (Review)
Review
Population aging is one of the most important demographic transformations of our time. Increasing the "health span"-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.
Topics: Humans; Aging; Cardiovascular Diseases; Cardiovascular System; Predictive Value of Tests; Age Factors; Aged; Healthy Aging; Prognosis; Middle Aged; Female; Male; Aged, 80 and over; Animals; Cellular Senescence
PubMed: 38597854
DOI: 10.1016/j.jcmg.2024.03.001 -
Cell Reports Jul 2023Aging impairs the capacity to respond to novel antigens, reducing immune protection against pathogens and vaccine efficacy. Dietary restriction (DR) extends life- and...
Aging impairs the capacity to respond to novel antigens, reducing immune protection against pathogens and vaccine efficacy. Dietary restriction (DR) extends life- and health span in diverse animals. However, little is known about the capacity of DR to combat the decline in immune function. Here, we study the changes in B cell receptor (BCR) repertoire during aging in DR and control mice. By sequencing the variable region of the BCR heavy chain in the spleen, we show that DR preserves diversity and attenuates the increase in clonal expansions throughout aging. Remarkably, mice starting DR in mid-life have repertoire diversity and clonal expansion rates indistinguishable from chronic DR mice. In contrast, in the intestine, these traits are unaffected by either age or DR. Reduced within-individual B cell repertoire diversity and increased clonal expansions are correlated with higher morbidity, suggesting a potential contribution of B cell repertoire dynamics to health during aging.
Topics: Mice; Animals; B-Lymphocytes; Aging; Receptors, Antigen, B-Cell
PubMed: 37384530
DOI: 10.1016/j.celrep.2023.112722 -
Epigenetics Dec 2023Occupational characteristics have been studied as risk factors for several age-related diseases and are thought to impact the ageing process, although there has been...
Occupational characteristics have been studied as risk factors for several age-related diseases and are thought to impact the ageing process, although there has been limited empirical work demonstrating an association between adverse occupational characteristics and accelerated ageing and this prior work has yielded mixed results. We used the 2010 and 2016 waves of the Health and Retirement Study ( = 1,251) to examine the association between occupation categories and self-reported working conditions of American adults at midlife and their subsequent epigenetic ageing as measured through five epigenetic clocks: PCHorvath, PCHannum, PCPhenoAge, PCGrimAge, and DunedinPACE. We found that individuals working in sales/clerical, service, and manual work show evidence of epigenetic age acceleration compared to those working in managerial/professional jobs and that the associations were stronger with second- and third-generation clocks. Individuals reporting high stress and high physical effort at work showed evidence of epigenetic age acceleration only on PCGrimAge and DunedinPACE. Most of these associations were attenuated after adjustment for race/ethnicity, educational attainment, and lifestyle-related risk factors. Sales/clerical work remained significantly associated with PCHorvath and PCHannum, while service work remained significantly associated with PCGrimAge. The results suggest that manual work and occupational physical activity may appear to be risk factors for epigenetic age acceleration through their associations with socioeconomic status, while stress at work may be a risk factor for epigenetic age acceleration through its associations with health behaviours outside of work. Additional work is needed to understand when in the life course and the specific mechanisms through which these associations occur.
Topics: Humans; United States; Aged; DNA Methylation; Aging; Ethnicity; Epigenesis, Genetic
PubMed: 37300823
DOI: 10.1080/15592294.2023.2218763 -
Aging Cell Oct 2023Aging has been considered as a risk factor in many diseases, thus, comprehensively understanding the cellular and molecular mechanisms of delayed aging is important....
Aging has been considered as a risk factor in many diseases, thus, comprehensively understanding the cellular and molecular mechanisms of delayed aging is important. Here we investigated whether Krüppel-like factor 14 (KLF14) is a suppressor of cellular senescence and aging. In our research, KLF14 levels significantly decreased not only in the lymphocytes of healthy people but also in the cells and tissues of mice with aging. We performed in vitro and in vivo experiments on cells and mice to reveal the function of KLF14 in aging. KLF14 deficiency facilitates cellular senescence and aging-related pathologies in C57BL/6J mice, whereas KLF14 overexpression attenuates cellular senescence. Mechanistically, KLF14 delays aging by binding to the POLD1 promoter to positively regulate POLD1 expression. Remarkably, cellular senescence mediated by KLF14 downregulation could be alleviated by POLD1 expression. In addition, perhexiline, an agonist of KLF14, could delay cellular senescence and aging-related pathologies in senescence-accelerated P8 mice by inducing POLD1 expression, as perhexiline could enhance the effect of KLF14's transcription activation to POLD1 by elevating the binding level of KLF14 to the POLD1 promoter. Our data indicate that KLF14 might be a critical element in aging by upregulating POLD1 expression, indicating that the activation of KLF14 may delay aging and aging-associated diseases.
Topics: Animals; Humans; Mice; Aging; Cellular Senescence; Down-Regulation; Kruppel-Like Transcription Factors; Mice, Inbred C57BL; Perhexiline
PubMed: 37551728
DOI: 10.1111/acel.13950 -
Journal of Internal Medicine May 2024The older population is increasing worldwide, and life expectancy is continuously rising, predominantly thanks to medical and technological progress. Healthspan refers... (Review)
Review
The older population is increasing worldwide, and life expectancy is continuously rising, predominantly thanks to medical and technological progress. Healthspan refers to the number of years an individual can live in good health. From a gerontological viewpoint, the mission is to extend the life spent in good health, promoting well-being and minimizing the impact of aging-related diseases to slow the aging process. Biologically, aging is a malleable process characterized by an intra- and inter-individual heterogeneous and dynamic balance between accumulating damage and repair mechanisms. Cellular senescence is a key component of this process, with senescent cells accumulating in different tissues and organs, leading to aging and age-related disease susceptibility over time. Removing senescent cells from the body or slowing down the burden rate has been proposed as an efficient way to reduce age-dependent deterioration. In animal models, senotherapeutic molecules can extend life expectancy and lifespan by either senolytic or senomorphic activity. Much research shows that dietary and physical activity-driven lifestyle interventions protect against senescence. This narrative review aims to summarize the current knowledge on targeting senescent cells to reduce the risk of age-related disease in animal models and their translational potential for humans. We focused on studies that have examined the potential role of senotherapeutics in slowing the aging process and modifying age-related disease burdens. The review concludes with a general discussion of the mechanisms underlying this unique trajectory and its implications for future research.
Topics: Animals; Humans; Clinical Relevance; Aging; Longevity; Life Expectancy; Cellular Senescence
PubMed: 38446642
DOI: 10.1111/joim.13775 -
Journal of Medical Ethics May 2024Räsänen draws a distinction between chronological age and biological age and argues that biological ageing is (sometimes) desirable. To demonstrate this, he asks us to...
Räsänen draws a distinction between chronological age and biological age and argues that biological ageing is (sometimes) desirable. To demonstrate this, he asks us to consider the case of April, who like Karel Čapek's Elina Makropulos, has stopped biologically ageing. Unlike Makropulos, though, April's biological ageing was halted before puberty, so she will never mature into adulthood. Räsänen contends this case shows ageing can be desirable, but this equivocates between maturing and ageing. Here I argue biological ageing, or the wear and tear normally associated with chronological ageing, is undesirable, but that maturing can be desirable.
Topics: Humans; Aging; Female; Sexual Maturation
PubMed: 37553223
DOI: 10.1136/jme-2023-109418 -
Current Molecular Medicine 2024In the last years, with the increase in the average life expectancy, the world's population is progressively aging, which entails social, health and economic problems.... (Review)
Review
In the last years, with the increase in the average life expectancy, the world's population is progressively aging, which entails social, health and economic problems. In this sense, the need to better understand the physiology of the aging process becomes an urgent need. Since the study of aging in humans is challenging, cellular and animal models are widely used as alternatives. Omics, namely metabolomics, have emerged in the study of aging, with the aim of biomarker discovering, which may help to uncomplicate this complex process. This paper aims to summarize different models used for aging studies with their advantages and limitations. Also, this review gathers the published articles referring to biomarkers of aging already discovered using metabolomics approaches, comparing the results obtained in the different studies. Finally, the most frequently used senescence biomarkers are described, along with their importance in understanding aging.
Topics: Humans; Metabolomics; Aging; Biomarkers; Animals; Cellular Senescence
PubMed: 37026499
DOI: 10.2174/1566524023666230407123727 -
Biomedical Journal Apr 2024
Topics: Humans; Cellular Senescence; Aging; Animals
PubMed: 38160717
DOI: 10.1016/j.bj.2023.100697 -
Biogerontology Dec 2023The Zbp1 gene has recently emerged as a potential therapeutic target for age-related diseases. Multiple studies have reported that Zbp1 plays a key role in regulating... (Review)
Review
The Zbp1 gene has recently emerged as a potential therapeutic target for age-related diseases. Multiple studies have reported that Zbp1 plays a key role in regulating several aging hallmarks, including cellular senescence, chronic inflammation, DNA damage response, and mitochondrial dysfunction. Regarding cellular senescence, Zbp1 appears to regulate the onset and progression of senescence by controlling the expression of key markers such as p16INK4a and p21CIP1/WAF1. Similarly, evidence suggests that Zbp1 plays a role in regulating inflammation by promoting the production of pro-inflammatory cytokines, such as IL-6 and IL-1β, through activation of the NLRP3 inflammasome. Furthermore, Zbp1 seems to be involved in the DNA damage response, coordinating the cellular response to DNA damage by regulating the expression of genes such as p53 and ATM. Additionally, Zbp1 appears to regulate mitochondrial function, which is crucial for energy production and cellular homeostasis. Given the involvement of Zbp1 in multiple aging hallmarks, targeting this gene represents a potential strategy to prevent or treat age-related diseases. For example, inhibiting Zbp1 activity could be a promising approach to reduce cellular senescence and chronic inflammation, two critical hallmarks of aging associated with various age-related diseases. Similarly, modulating Zbp1 expression or activity could also improve DNA damage response and mitochondrial function, thus delaying or preventing the development of age-related diseases. Overall, the Zbp1 gene appears to be a promising therapeutic target for age-related diseases. In the current review, we have discussed the molecular mechanisms underlying the involvement of Zbp1 in aging hallmarks and proposed to develop effective strategies to target this gene for therapeutic purposes.
Topics: Humans; Aging; Cellular Senescence; Mitochondria; Inflammation
PubMed: 37199888
DOI: 10.1007/s10522-023-10039-w -
Human Reproduction (Oxford, England) Oct 2023In modern post-transition societies, we are reproducing later and living longer. While the impact of age on female reproductive function has been well studied, much less...
In modern post-transition societies, we are reproducing later and living longer. While the impact of age on female reproductive function has been well studied, much less is known about the intersection of age and male reproduction. Our current understanding is that advancing age brings forth a progressive decline in male fertility accompanied by a reduction in circulating testosterone levels and the appearance of age-dependent reproductive pathologies including benign prostatic hypertrophy and erectile dysfunction. Paternal ageing is also associated with a profound increase in sperm DNA damage, the appearance of multiple epigenetic changes in the germ line and an elevated mutational load in the offspring. The net result of such changes is an increase in the disease burden carried by the progeny of ageing males, including dominant genetic diseases such as Apert syndrome and achondroplasia, as well as neuropsychiatric conditions including autism and spontaneous schizophrenia. The genetic basis of these age-related effects appears to involve two fundamental mechanisms. The first is a positive selection mechanism whereby stem cells containing mutations in a mitogen-activated protein kinase pathway gain a selective advantage over their non-mutant counterparts and exhibit significant clonal expansion with the passage of time. The second is dependent on an age-dependent increase in oxidative stress which impairs the steroidogenic capacity of the Leydig cells, disrupts the ability of Sertoli cells to support the normal differentiation of germ cells, and disrupts the functional and genetic integrity of spermatozoa. Given the central importance of oxidative stress in defining the impact of chronological age on male reproduction, there may be a role for antioxidants in the clinical management of this process. While animal studies are supportive of this strategy, carefully designed clinical trials are now needed if we are to realize the therapeutic potential of this approach in a clinical context.
Topics: Animals; Male; Female; Semen; Reproduction; Aging; Spermatozoa; Mutation
PubMed: 37568254
DOI: 10.1093/humrep/dead157