Immunomodulatory and Antiaging Mechanisms of Resveratrol, Rapamycin, and Metformin: Focus on mTOR and AMPK Signaling Networks DOI Creative Commons
Vincenzo Sorrenti, Francesca Benedetti, Alessandro Buriani

et al.

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(8), P. 912 - 912

Published: July 23, 2022

Aging results from the progressive dysregulation of several molecular pathways and mTOR AMPK signaling have been suggested to play a role in complex changes key biological networks involved cellular senescence. Moreover, multiple factors, including poor nutritional balance, drive immunosenescence progression, one meaningful aspects aging. Unsurprisingly, nutraceutical pharmacological interventions could help maintain an optimal response by providing essential bioactive micronutrients required for development, maintenance, expression immune at all stages life. In this regard, many studies provided evidence potential antiaging properties resveratrol, as well rapamycin metformin. Indeed, vitro vivo models demonstrated these molecules number positive effects associated with healthy The current review focuses on mechanisms action three important compounds their use clinical treatment

Language: Английский

Accelerated aging in bipolar disorder: A comprehensive review of molecular findings and their clinical implications DOI
Gabriel R. Fries,

Madeline J. Zamzow,

Taylor Andrews

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2020, Volume and Issue: 112, P. 107 - 116

Published: Feb. 1, 2020

Language: Английский

Citations

85
Metformin as an anti-inflammatory agent: a short review DOI Open Access

Robin Kristófi,

Jan W. Eriksson

Journal of Endocrinology, Journal Year: 2021, Volume and Issue: 251(2), P. R11 - R22

Published: Aug. 31, 2021

Metformin is a biguanide drug widely used as the initial treatment of type 2 diabetes. Despite its widespread use, precise mechanisms action remain incompletely characterised. Its effect in lowering blood glucose largely related to suppression gluconeogenesis liver, which probably accomplished by partial inhibition mitochondrial respiratory chain complex 1 with subsequent increase intracellular AMP levels and activation kinase. Several local systemic anti-inflammatory effects metformin have been described. Many these seem be mediated kinase downstream inhibiting mTOR NF-κB pro-inflammatory signalling cascades. However, there are also studies describing actions independent action. In this review, we summarise currently known on inflammatory pathways clinical evidence underpinning use potential drug.

Language: Английский

Citations

82
Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity, Skin Health and Cellular Senescence DOI Open Access
Jacqueline L. Boyajian, Merry Ghebretatios, Sabrina Schaly

et al.

Nutrients, Journal Year: 2021, Volume and Issue: 13(12), P. 4550 - 4550

Published: Dec. 18, 2021

The role of the microbiome in human aging is important: directly impacts through gastrointestinal system. However, microbial impact on skin has yet to be fully understood. For example, cellular senescence an intrinsic process that been recently associated with imbalance. With age, cells become senescent response stress wherein they undergo irreversible growth arrest while maintaining high metabolic activity. An accumulation linked various and chronic pathologies due overexpression senescence-associated secretory phenotype (SASP) comprised proinflammatory cytokines, chemokines, factors, proteases, lipids extracellular matrix components. In particular, dermatological disorders may promoted by as a common site accumulation. gut microbiota influences disruption gut-skin axis secretion metabolites. Metabolomics can used identify quantify metabolites involved senescence. Moreover, novel anti-senescent therapeutics are warranted given poor safety profiles current pharmaceutical drugs. Probiotics prebiotics effective alternatives, considering relationship between healthy aging. further research composition under status needed develop immunomodulatory therapies.

Language: Английский

Citations

82
Cardiovascular Aging and Longevity DOI Creative Commons

P Pietri,

Christodoulos Stefanadis

Journal of the American College of Cardiology, Journal Year: 2021, Volume and Issue: 77(2), P. 189 - 204

Published: Jan. 1, 2021

Language: Английский

Citations

67
Mitochondria-targeted senotherapeutic interventions DOI
Mehmet Can Atayik, Ufuk Çakatay

Biogerontology, Journal Year: 2022, Volume and Issue: 23(4), P. 401 - 423

Published: July 4, 2022

Language: Английский

Citations

42
Gene Therapy Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice DOI Open Access

Carolina Cano Macip,

Rokib Hasan,

Victoria Hoznek

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 5, 2023

Abstract Aging is a complex process best characterized as the chronic dysregulation of cellular processes leading to deteriorated tissue and organ function. While aging cannot currently be prevented, its impact on lifespan healthspan in elderly can potentially minimized by interventions that aim return these optimal Recent studies have demonstrated partial reprogramming using Yamanaka factors (or subset; OCT4, SOX2 , KLF4; OSK) reverse age-related changes vitro vivo . However, it still unknown whether subset) are capable extending aged wild type mice. Here, we show systemically delivered AAVs, encoding an inducible OSK system, 124-week-old mice extends median remaining 109% over wild-type controls enhances several health parameters. Importantly, observed significant improvement frailty scores indicating were able improve along with increasing lifespan. Furthermore, human keratinocytes expressing exogenous OSK, epigenetic markers age-reversal, suggesting potential reregulation genetic networks younger, healthier state. Together, results may important implications for development age-associated diseases elderly.

Language: Английский

Citations

23
Current perspectives on the cellular and molecular features of epigenetic ageing DOI
Ken Raj, Steve Horvath

Experimental Biology and Medicine, Journal Year: 2020, Volume and Issue: 245(17), P. 1532 - 1542

Published: April 10, 2020

It has been noted for quite some time that DNA methylation levels decline with age. The significance of this change remained unknown until it became possible to measure status specific sites on the DNA. was observed while does indeed decrease age, others increase or remain unchanged. application machine learning methods these quantitative changes in multiple sites, allowed generation a highly accurate estimator called epigenetic clock. clock large human epidemiological data sets revealed discordance between predicted (epigenetic age) and chronological age is associated many age-related pathologies, particularly when former greater than latter. clearly captures degree, biological features accompany ageing process. Despite ever-increasing scope pathologies are found be accelerated ageing, basic principles underlie ticking elusive. Here, we describe known molecular cellular attributes consider their properties, proffer opinions as how they may connected what might underlying mechanism. Emerging from considerations inescapable view begins very early moments after embryonic stem cell stage continues un-interrupted through entire life-course. This appears consequence processes necessary development organism conception maintain thereafter homeostasis. Hence, speed can, affected by external factors, essence process itself an integral part of, life. Impact statement field relatively new, its expansion presents challenge keeping abreast new discoveries implications. Several reviews have already addressed great number health conditions, life-style, stressors rate ageing. While associations highlight affirm ability capture biologically meaningful do not inform us about mechanisms. In period since clock, there rather limited experimental research aimed at uncovering perspective derived available but nevertheless lines evidence together provide seemingly coherent narrative can tested. This, believe would helpful towards workings

Language: Английский

Citations

68
Pharmacology of metformin – An update DOI
Hartmut Glossmann, O. Lutz

European Journal of Pharmacology, Journal Year: 2019, Volume and Issue: 865, P. 172782 - 172782

Published: Nov. 6, 2019

Language: Английский

Citations

55
Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia DOI Creative Commons
Pasquale Mone, Jessica Gambardella,

Antonella Pansini

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(8), P. 2115 - 2115

Published: Aug. 17, 2021

Endothelial dysfunction is a key hallmark of hypertension, which leading risk factor for cognitive decline in older adults with or without frailty. Similarly, hyperglycemia known to impair endothelial function and predictor severe cardiovascular outcomes, independent the presence diabetes. On these grounds, we designed study assess effects high-glucose metformin on brain microvascular cells (ECs) impairment frail hypertensive patients. We tested high-glucose-induced cell death, permeability, generation reactive oxygen species vitro, human ECs. To investigate consequences clinical scenario, recruited patients evaluated their Montreal Cognitive Assessment (MoCA) scores, comparing them according glycemic status (normoglycemic vs. hyperglycemic) use metformin. enrolled 376 patients, 209 successfully completed study. observed significant correlation between MoCA score glycemia. found that hyperglycemic treated had significantly better than insulin (18.32 ± 3.9 14.94 3.8; p < 0.001). Our vitro assays confirmed beneficial our knowledge, this first correlating glycemia adults, showing aggravates impairment.

Language: Английский

Citations

54
Reproductive Longevity and Aging: Geroscience Approaches to Maintain Long-Term Ovarian Fitness DOI Creative Commons
Natalia C. Llarena, Christopher Hine

The Journals of Gerontology Series A, Journal Year: 2020, Volume and Issue: 76(9), P. 1551 - 1560

Published: Aug. 18, 2020

Increases in delayed childbearing worldwide have elicited the need for a better understanding of biological underpinnings and implications age-related infertility. In women 35 years older incidences infertility, aneuploidy, birth defects dramatically increase. These outcomes are result declines both ovarian reserve oocyte quality. addition to waning reproductive function, decline estrogen secretion at menopause contributes multisystem aging initiation frailty. Both hormonal function limited by primordial follicle pool, which is established utero irreversibly until menopause. Because dependent on an mechanisms that regulate follicular growth maintenance pool critical development interventions prolong life span. Multiple pathways related nutrient-sensing converge mammalian ovary quiescence or activation follicles. The PI3K/PTEN/AKT/FOXO3 associated TSC/mTOR central regulation pool; however, aging-associated systems such as insulin-like factor-1/growth hormone pathway, transsulfuration/hydrogen sulfide may also play role. Additionally, sirtuins aid maintaining developmental metabolic competence chromosomal integrity oocyte. Here we review quality, discuss geroscience leverage our these promote longevity.

Language: Английский

Citations

52