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Nature Reviews. Molecular Cell Biology Jan 2022Dietary restriction with adequate nutrition is the gold standard for delaying ageing and extending healthspan and lifespan in diverse species, including rodents and... (Review)
Review
Dietary restriction with adequate nutrition is the gold standard for delaying ageing and extending healthspan and lifespan in diverse species, including rodents and non-human primates. In this Review, we discuss the effects of dietary restriction in these mammalian model organisms and discuss accumulating data that suggest that dietary restriction results in many of the same physiological, metabolic and molecular changes responsible for the prevention of multiple ageing-associated diseases in humans. We further discuss how different forms of fasting, protein restriction and specific reductions in the levels of essential amino acids such as methionine and the branched-chain amino acids selectively impact the activity of AKT, FOXO, mTOR, nicotinamide adenine dinucleotide (NAD), AMP-activated protein kinase (AMPK) and fibroblast growth factor 21 (FGF21), which are key components of some of the most important nutrient-sensing geroprotective signalling pathways that promote healthy longevity.
Topics: Animals; Caloric Restriction; Disease Models, Animal; Health; Humans; Longevity; Oxidative Stress
PubMed: 34518687
DOI: 10.1038/s41580-021-00411-4 -
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 -
Human Genetics Mar 2020Our understanding of the process of autophagy and its role in health and diseases has grown remarkably in the last two decades. Early work established autophagy as a... (Review)
Review
Our understanding of the process of autophagy and its role in health and diseases has grown remarkably in the last two decades. Early work established autophagy as a general bulk recycling process which involves the sequestration and transport of intracellular material to the lysosome for degradation. Currently, autophagy is viewed as a nexus of metabolic and proteostatic signalling that can determine key physiological decisions from cell fate to organismal lifespan. Here, we review the latest literature on the role of autophagy and lysosomes in stress response and longevity. We highlight the connections between autophagy and metabolic processes, the network associated with its regulation, and the links between autophagic dysfunction, neurodegenerative diseases, and aging.
Topics: Aging; Animals; Autophagy; Humans; Longevity; Lysosomes; Signal Transduction
PubMed: 31144030
DOI: 10.1007/s00439-019-02031-7 -
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 -
Aging Apr 2018Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological...
Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
Topics: Aging; Biomarkers; Epigenesis, Genetic; Humans; Longevity
PubMed: 29676998
DOI: 10.18632/aging.101414 -
Developmental Cell May 2021Lipids play crucial roles in regulating aging and longevity. In the past few decades, a series of genetic pathways have been discovered to regulate lifespan in model... (Review)
Review
Lipids play crucial roles in regulating aging and longevity. In the past few decades, a series of genetic pathways have been discovered to regulate lifespan in model organisms. Interestingly, many of these regulatory pathways are linked to lipid metabolism and lipid signaling. Lipid metabolic enzymes undergo significant changes during aging and are regulated by different longevity pathways. Lipids also actively modulate lifespan and health span as signaling molecules. In this review, we summarize recent insights into the roles of lipid metabolism and lipid signaling in aging and discuss lipid-related interventions in promoting longevity.
Topics: Animals; Humans; Lipid Metabolism; Lipids; Lipoproteins; Longevity; Receptors, Cell Surface; Signal Transduction
PubMed: 33891896
DOI: 10.1016/j.devcel.2021.03.034 -
Biochimica Et Biophysica Acta.... Mar 2020Aging is the main risk factor for chronic diseases and disablement in human societies with a great impact in social and health care expenditures. So far, aging and,... (Review)
Review
Aging is the main risk factor for chronic diseases and disablement in human societies with a great impact in social and health care expenditures. So far, aging and, eventually, death are unavoidable. Nevertheless, research efforts on aging-associated diseases with the aim not only to extend life span but also to increment health span in an attempt to delay, stop and even reverse the aging process have not stopped growing. Caloric restriction extends both health and life span in several short-lived experimental models and has brought to light the role of different molecular effectors involved in nutrient sensing pathways and longevity. This opens the possibility of modulating these molecular effectors also in humans to increase longevity and health span. The difficulty to implement caloric restricted diets in humans has led to the development of new bearable diets such as time-restricted feeding, intermittent fasting or diets with limited amounts of some nutrients and to the search of pharmacological agents, targeted to the effectors that mediate the extension of life and health span in response to these anti-aging diets. Pharmacological approaches that eliminate senescent cells or prevent primary causes of aging such as telomere attrition also emerge as potential anti-aging strategies. In the present article, we review these possible nutritional and pharmacological interventions designed to mitigate and/or delay the aging process and to increase health and life span.
Topics: Aging; Animals; Caloric Restriction; Chronic Disease; Diet; Fasting; Humans; Longevity
PubMed: 31816437
DOI: 10.1016/j.bbadis.2019.165612 -
Revista de Investigacion Clinica;... 2016As human life expectancy is prolonged, age-related diseases are thriving. Aging is a complex multifactorial process of molecular and cellular decline that affects tissue... (Review)
Review
As human life expectancy is prolonged, age-related diseases are thriving. Aging is a complex multifactorial process of molecular and cellular decline that affects tissue function over time, rendering organisms frail and susceptible to disease and death. Over the last decades, a growing body of scientific literature across different biological models, ranging from yeast, worms, flies, and mice to primates, humans and other long-lived animals, has contributed greatly towards identifying conserved biological mechanisms that ward off structural and functional deterioration within living systems. Collectively, these data offer powerful insights into healthy aging and longevity. For example, molecular integrity of the genome, telomere length, epigenetic landscape stability, and protein homeostasis are all features linked to "youthful" states. These molecular hallmarks underlie cellular functions associated with aging like mitochondrial fitness, nutrient sensing, efficient intercellular communication, stem cell renewal, and regenerative capacity in tissues. At present, calorie restriction remains the most robust strategy for extending health and lifespan in most biological models tested. Thus, pathways that mediate the beneficial effects of calorie restriction by integrating metabolic signals to aging processes have received major attention, such as insulin/insulin growth factor-1, sirtuins, mammalian target of rapamycin, and 5' adenosine monophosphate-activated protein kinase. Consequently, small-molecule targets of these pathways have emerged in the impetuous search for calorie restriction mimetics, of which resveratrol, metformin, and rapamycin are the most extensively studied. A comprehensive understanding of the molecular and cellular mechanisms that underlie age-related deterioration and repair, and how these pathways interconnect, remains a major challenge for uncovering interventions to slow human aging while extending molecular and physiological youthfulness, vitality, and health. This review summarizes key molecular mechanisms underlying the biology of healthy aging and longevity.
Topics: Age Factors; Aging; Animals; Caloric Restriction; Humans; Life Expectancy; Longevity; Mice; Models, Biological
PubMed: 27028172
DOI: No ID Found -
The Lancet. Healthy Longevity Nov 2022Intrinsic capacity, a crucial concept in healthy ageing, is defined by WHO as "the composite of all the physical and mental capacities that an individual can draw on at... (Review)
Review
Intrinsic capacity, a crucial concept in healthy ageing, is defined by WHO as "the composite of all the physical and mental capacities that an individual can draw on at any point in time". Vitality capacity is considered the underlying physiological determinant of intrinsic capacity. To advance the measurement and monitoring of vitality capacity, a working group of WHO staff members and twenty experts representing six WHO regions was convened to discuss and clarify the attributes of vitality capacity and to develop a clear working definition of the concept. Potential biomarkers to measure vitality capacity were identified, and the following consensual working definition was developed: vitality capacity is a physiological state (due to normal or accelerated biological ageing processes) resulting from the interaction between multiple physiological systems, reflected in (the level of) energy and metabolism, neuromuscular function, and immune and stress response functions of the body.
Topics: Humans; Longevity; Health Status; Aging; Healthy Aging; World Health Organization
PubMed: 36356628
DOI: 10.1016/S2666-7568(22)00200-8 -
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