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Genes Jul 2019Research on longevity and healthy aging promises to increase our lifespan and decrease the burden of degenerative diseases with important social and economic effects.... (Review)
Review
Research on longevity and healthy aging promises to increase our lifespan and decrease the burden of degenerative diseases with important social and economic effects. Many aging theories have been proposed, and important aging pathways have been discovered. Model organisms have had a crucial role in this process because of their short lifespan, cheap maintenance, and manipulation possibilities. Yeasts, worms, fruit flies, or mammalian models such as mice, monkeys, and recently, dogs, have helped shed light on aging processes. Genes and molecular mechanisms that were found to be critical in simple eukaryotic cells and species have been confirmed in humans mainly by the functional analysis of mammalian orthologues. Here, we review conserved aging mechanisms discovered in different model systems that are implicated in human longevity as well and that could be the target of anti-aging interventions in human.
Topics: Aging; Animals; Biomarkers; Cellular Senescence; Drosophila; Eukaryota; Humans; Longevity; Mammals; Models, Animal; Models, Biological; Signal Transduction; Yeasts
PubMed: 31324014
DOI: 10.3390/genes10070518 -
Human Genetics Dec 2013Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of... (Review)
Review
Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and rare alleles, with impeccable control for population stratification and consideration of non-genetic factors such as environment.
Topics: Aging; Epigenesis, Genetic; Gene-Environment Interaction; Genetic Linkage; Genetic Variation; Genome-Wide Association Study; Health; Humans; Life Expectancy; Longevity
PubMed: 23925498
DOI: 10.1007/s00439-013-1342-z -
Plant Foods For Human Nutrition... Mar 2022Diet provides energy and nutrition for human survival, and also provides various joy of taste. Extensive studies have shown that the major components of diet, such as... (Review)
Review
Diet provides energy and nutrition for human survival, and also provides various joy of taste. Extensive studies have shown that the major components of diet, such as protein, carbohydrate and fat, play important roles in regulating aging and longevity. Whether other dietary ingredients can help prevent aging and extend longevity is a very interesting question. Here based on recent findings, we discussed dietary plant ingredients that can extend longevity by regulation of metabolism, targeting TRP channels, mitophagy, senescence pathways and circadian rhythms. Better understanding of the detailed effects and mechanisms of dietary ingredients on longevity regulation, would be helpful for developing new intervention tools for preventing aging and aging related diseases.
Topics: Diet; Longevity; Phytochemicals
PubMed: 35025006
DOI: 10.1007/s11130-021-00946-z -
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 -
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 -
International Journal of Molecular... Sep 2019Aging is a natural phenomenon that occurs in all living organisms. In humans, aging is associated with lowered overall functioning and increased mortality out of the... (Review)
Review
Aging is a natural phenomenon that occurs in all living organisms. In humans, aging is associated with lowered overall functioning and increased mortality out of the risk for various age-related diseases. Hence, researchers are pushed to find effective natural interventions that can promote healthy aging and extend lifespan. Royal jelly (RJ) is a natural product that is fed to bee queens throughout their entire life. Thanks to RJ, bee queens enjoy an excellent reproductive function and lengthened lifespan compared with bee workers, despite the fact that they have the same genome. This review aimed to investigate the effect of RJ and/or its components on lifespan/healthspan in various species by evaluating the most relevant studies. Moreover, we briefly discussed the positive effects of RJ on health maintenance and age-related disorders in humans. Whenever possible, we explored the metabolic, molecular, and cellular mechanisms through which RJ can modulate age-related mechanisms to extend lifespan. RJ and its ingredients-proteins and their derivatives e.g., royalactin; lipids e.g., 10-hydroxydecenoic acid; and vitamins e.g., pantothenic acid-improved healthspan and extended lifespan in worker honeybees , flies, crickets, silkworms, nematodes, and mice. The longevity effect was attained via various mechanisms: downregulation of insulin-like growth factors and targeting of rapamycin, upregulation of the epidermal growth factor signaling, dietary restriction, and enhancement of antioxidative capacity. RJ and its protein and lipid ingredients have the potential to extend lifespan in various creatures and prevent senescence of human tissues in cell cultures. These findings pave the way to inventing specific RJ anti-aging drugs. However, much work is needed to understand the effect of RJ interactions with microbiome, diet, activity level, gender, and other genetic variation factors that affect healthspan and longevity.
Topics: Animals; Fatty Acids; Female; Humans; Longevity; Male; Models, Biological
PubMed: 31547049
DOI: 10.3390/ijms20194662 -
Nature Jul 2019For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented... (Review)
Review
For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. Here we summarize the milestones that mark this scientific triumph, discuss different ageing pathways and processes, and suggest that ageing research is entering a new era that has unique medical, commercial and societal implications. We argue that this era marks an inflection point, not only in ageing research but also for all biological research that affects the human healthspan.
Topics: Aging; Biomedical Research; Circadian Clocks; Clinical Trials as Topic; Healthy Aging; Humans; Inflammation; Longevity; Mitochondria; Nutritional Status; Oxidative Stress; Rejuvenation; Signal Transduction
PubMed: 31292558
DOI: 10.1038/s41586-019-1365-2 -
The Journals of Gerontology. Series A,... Nov 2019Interventions meant to promote longevity and healthy aging have often been designed or observed to modulate very specific gene or protein targets. If there are naturally... (Review)
Review
Interventions meant to promote longevity and healthy aging have often been designed or observed to modulate very specific gene or protein targets. If there are naturally occurring genetic variants in such a target that affect longevity as well as the molecular function of that target (eg, the variants influence the expression of the target, acting as "expression quantitative trait loci" or "eQTLs"), this could support a causal relationship between the pharmacologic modulation of the target and longevity and thereby validate the target at some level. We considered the gene targets of many pharmacologic interventions hypothesized to enhance human longevity and explored how many variants there are in those targets that affect gene function (eg, as expression quantitative trait loci). We also determined whether variants in genes associated with longevity-related phenotypes affect gene function or are in linkage disequilibrium with variants that do, and whether pharmacologic studies point to compounds exhibiting activity against those genes. Our results are somewhat ambiguous, suggesting that integrating genetic association study results with functional genomic and pharmacologic studies is necessary to shed light on genetically mediated targets for longevity-enhancing drugs. Such integration will require more sophisticated data sets, phenotypic definitions, and bioinformatics approaches to be useful.
Topics: Forecasting; Humans; Longevity; Preliminary Data; Quantitative Trait Loci
PubMed: 31724058
DOI: 10.1093/gerona/glz206 -
Mechanisms of Ageing and Development Jan 1990The phenomenon of longevity hormesis is reviewed. The life-prolonging effects of longevity hormesis are compared and contrasted with those resulting from depressed food... (Review)
Review
The phenomenon of longevity hormesis is reviewed. The life-prolonging effects of longevity hormesis are compared and contrasted with those resulting from depressed food intake. The use of age-specific mortality rate analysis as a tool to characterize the separate and distinct effects of longevity hormesis, cumulative toxicity and depressed food intake on the survival of laboratory animals is illustrated. Finally, model systems through which the mechanism(s) of longevity hormesis may be elucidated are discussed.
Topics: Animals; Longevity; Toxins, Biological
PubMed: 2405215
DOI: 10.1016/0047-6374(90)90158-c -
Interdisciplinary Topics in Gerontology 2014Regulation of longevity depends on genetic and environmental factors. According to Svanborg, a Swedish geriatrician, over the last decades human life expectancy... (Review)
Review
Regulation of longevity depends on genetic and environmental factors. According to Svanborg, a Swedish geriatrician, over the last decades human life expectancy increased as well as the age at onset of fatal diseases. Nevertheless, autopsies of centenarians revealed the presence of several severe pathologies which could have killed them much earlier. Therefore, the emphasis is on regulation of resistance dependent on the expression of genes such as Sirtuins, mTOR pathway and others controlling body resistance. Only a small fraction (<1%) of centenarians live to become supercentenarians (110 years), indicating a limit of performance and resistance of the body. This limit can be interpreted as 'tinkering' of nature instead of producing masterpieces as suggested by F. Jacob. These facts and theories are described in this chapter.
Topics: Aged, 80 and over; Aging; Biological Evolution; Elastin; Environment; Humans; Life Style; Longevity; Sirtuins
PubMed: 24862022
DOI: 10.1159/000358907