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Cell Metabolism Jan 2020
Topics: Diabetes Mellitus; Editorial Policies; Humans; Liver Diseases; Longevity; Microbiota; Neoplasms
PubMed: 31914375
DOI: 10.1016/j.cmet.2019.12.010 -
Biochemistry. Biokhimiia Dec 2016The mitochondrial genome provides not only respiratory chain function, but it also ensures the impact of mitochondria on nearly all crucial metabolic processes. It is... (Review)
Review
The mitochondrial genome provides not only respiratory chain function, but it also ensures the impact of mitochondria on nearly all crucial metabolic processes. It is well known that mitochondria regulate aging and lifespan. However, until now there were no direct experimental data concerning the influence of various mitochondrial DNA variants on lifespan of animals with identical nuclear genome. In a recent paper of J. A. Enríquez and coworkers (Latorre-Pellicer, A., et al. (2016) Nature, 535, 561-565), it was shown that mice carrying nuclear DNA from one strain and mitochondrial DNA from another had longer median lifespan and retarded development of various aging traits. This review critically analyzes that paper and considers some aspects of the crosstalk between the nuclear and mitochondrial genomes. We also discuss new perspectives of gerontology in the light of the discovery made by Enríquez's group.
Topics: Aging; Animals; DNA, Mitochondrial; Evolution, Molecular; Genetic Association Studies; Genome, Mitochondrial; Humans; Longevity; Reactive Oxygen Species
PubMed: 28259117
DOI: 10.1134/S0006297916120014 -
Journal of the American College of... Jan 2021Cardiovascular aging and longevity are interrelated through many pathophysiological mechanisms. Many factors that promote atherosclerotic cardiovascular disease are also... (Review)
Review
Cardiovascular aging and longevity are interrelated through many pathophysiological mechanisms. Many factors that promote atherosclerotic cardiovascular disease are also implicated in the aging process and vice versa. Indeed, cardiometabolic disorders such as hyperglycemia, insulin resistance, dyslipidemia, and arterial hypertension share common pathophysiological mechanisms with aging and longevity. Moreover, genetic modulators of longevity have a significant impact on cardiovascular aging. The current knowledge of genetic, molecular, and biochemical pathways of aging may serve as a substrate to introduce interventions that might delay cardiovascular aging, thus approaching the goal of longevity. In the present review, the authors describe pathophysiological links between cardiovascular aging and longevity and translate these mechanisms into clinical data by reporting genetic, dietary, and environmental characteristics from long-living populations.
Topics: Cardiovascular System; Environment; Epigenesis, Genetic; Healthy Lifestyle; Humans; Longevity
PubMed: 33446313
DOI: 10.1016/j.jacc.2020.11.023 -
Gerontology 2020Across species, development and longevity are tightly linked. We discuss the relevant literature and suggest that the root for this stringent relationship is the rate of... (Review)
Review
Across species, development and longevity are tightly linked. We discuss the relevant literature and suggest that the root for this stringent relationship is the rate of development. The basis for the relationship between rate of development and longevity lies in adaptations that have occurred through evolution at multiple levels of biological complexity: organism, organ, cellular, and molecular. Thus, the analysis of the relationship is of interest for multiple fields of biology.
Topics: Aging; Animals; Cellular Senescence; Humans; Longevity; Telomere
PubMed: 32036369
DOI: 10.1159/000505327 -
International Journal of Molecular... May 2022Several studies on the genetics of longevity have been reviewed in this paper. The results show that, despite efforts and new technologies, only two genes, APOE and... (Review)
Review
Several studies on the genetics of longevity have been reviewed in this paper. The results show that, despite efforts and new technologies, only two genes, APOE and FOXO3A, involved in the protection of cardiovascular diseases, have been shown to be associated with longevity in nearly all studies. This happens because the genetic determinants of longevity are dynamic and depend on the environmental history of a given population. In fact, population-specific genes are thought to play a greater role in the attainment of longevity than those shared between different populations. Hence, it is not surprising that GWAS replicated associations of common variants with longevity have been few, if any, as these studies pool together different populations. An alternative way might be the study of long-life families. This type of approach is proving to be an ideal resource for uncovering protective alleles and associated biological signatures for healthy aging phenotypes and exceptional longevity.
Topics: Genetics, Population; Healthy Aging; Longevity; Phenotype
PubMed: 35628444
DOI: 10.3390/ijms23105635 -
Philosophical Transactions of the Royal... Dec 1997A broad biological approach makes it possible to understand why ageing exists and also why different mammalian species have very different maximum longevities. The adult... (Review)
Review
A broad biological approach makes it possible to understand why ageing exists and also why different mammalian species have very different maximum longevities. The adult organism is maintained in a functional state by at least ten major mechanisms, which together comprise a substantial proportion of all biological processes. These maintenance mechanisms eventually fail, because the evolved physiological and anatomical design of higher animals is incompatible with continual survival. The lifespan of each mammalian species depends on the efficiency of maintenance of their cells, tissues and organisms, and there is much evidence that such maintenance is more effective in long-lived species, such as man, than in short-lived small mammals. It is also evident that there is an inverse relationship between reproductive potential and longevity, which would be expected if total metabolic resources are shared between investment in reproduction, and investment in the preservation of the adult body. It is proposed that the eventual failure of maintenance leads to the pathological changes seen in age-associated disease. Although we now have a biological understanding of the ageing process, much future research will be needed to uncover the cellular and molecular changes which give rise to age-associated diseases. The major aim of such research is to devise procedures to delay or prevent the onset of these diseases.
Topics: Adult; Aging; Animals; Biological Evolution; Disease; Humans; Life Expectancy; Longevity; Mammals; Models, Biological; Reproduction
PubMed: 9460062
DOI: 10.1098/rstb.1997.0163 -
Nature Jul 2009Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies;...
Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.
Topics: Administration, Oral; Aging; Animals; Carrier Proteins; Diet; Disease Susceptibility; Female; Longevity; Male; Mice; Phosphotransferases (Alcohol Group Acceptor); Sirolimus; Specific Pathogen-Free Organisms; Survival Analysis; TOR Serine-Threonine Kinases; Time Factors
PubMed: 19587680
DOI: 10.1038/nature08221 -
Medecine Sciences : M/S 2022New approaches allow precise measurement of somatic mutations in tissues. Applied to a diverse set of mammals, these methods show that somatic mutation load increases...
New approaches allow precise measurement of somatic mutations in tissues. Applied to a diverse set of mammals, these methods show that somatic mutation load increases with age (as expected) but reaches similar levels near the end of life for animals with extremely different longevity. This is an important result that has many repercussions on concepts of aging and of evolution of longevity.
Topics: Aging; Animals; Longevity; Mammals; Mutation
PubMed: 36094245
DOI: 10.1051/medsci/2022098 -
Annual Review of Animal Biosciences Feb 2023Naked mole-rats (NMRs, ) are the longest-lived rodents with a maximum life span exceeding 37 years. They exhibit a delayed aging phenotype and resistance to age-related... (Review)
Review
Naked mole-rats (NMRs, ) are the longest-lived rodents with a maximum life span exceeding 37 years. They exhibit a delayed aging phenotype and resistance to age-related functional decline/diseases. Specifically, they do not display increased mortality with age, maintain several physiological functions until nearly the end of their lifetime, and rarely develop cancer and Alzheimer's disease. NMRs live in a hypoxic environment in underground colonies in East Africa and are highly tolerant of hypoxia. These unique characteristics of NMRs have attracted considerable interest from zoological and biomedical researchers. This review summarizes previous studies of the ecology, hypoxia tolerance, longevity/delayed aging, and cancer resistance of NMRs and discusses possible mechanisms contributing to their healthy aging. In addition, we discuss current issues and future perspectives to fully elucidate the mechanisms underlying delayed aging and resistance to age-related diseases in NMRs.
Topics: Animals; Healthy Aging; Aging; Longevity; Mole Rats; Hypoxia
PubMed: 36318672
DOI: 10.1146/annurev-animal-050322-074744 -
Cell Reports Sep 2023The naked mole rat (NMR) is the longest-lived rodent, resistant to multiple age-related diseases including neurodegeneration. However, the mechanisms underlying the...
The naked mole rat (NMR) is the longest-lived rodent, resistant to multiple age-related diseases including neurodegeneration. However, the mechanisms underlying the NMR's resistance to neurodegenerative diseases remain elusive. Here, we isolated oligodendrocyte progenitor cells (OPCs) from NMRs and compared their transcriptome with that of other mammals. Extracellular matrix (ECM) genes best distinguish OPCs of long- and short-lived species. Notably, expression levels of CD44, an ECM-binding protein that has been suggested to contribute to NMR longevity by mediating the effect of hyaluronan (HA), are not only high in OPCs of long-lived species but also positively correlate with longevity in multiple cell types/tissues. We found that CD44 localizes to the endoplasmic reticulum (ER) and enhances basal ATF6 activity. CD44 modifies proteome and membrane properties of the ER and enhances ER stress resistance in a manner dependent on unfolded protein response regulators without the requirement of HA. HA-independent role of CD44 in proteostasis regulation may contribute to mammalian longevity.
Topics: Animals; Longevity; Endoplasmic Reticulum Stress; Unfolded Protein Response; Transcriptome; Mole Rats
PubMed: 37708026
DOI: 10.1016/j.celrep.2023.113130