Blood-derived mitochondrial DNA copy number is associated with Alzheimer disease, Alzheimer-related biomarkers and serum metabolites DOI Creative Commons
Tong Tong, Congcong Zhu, John J. Farrell

et al.

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Oct. 23, 2024

Blood-derived mitochondrial DNA copy number (mtDNA-CN) is a proxy measurement of function in the peripheral and central systems. Abnormal mtDNA-CN not only indicates impaired mtDNA replication transcription machinery but also dysregulated biological processes such as energy lipid metabolism. However, relationship between Alzheimer disease (AD) unclear. We performed two-sample Mendelian randomization (MR) using publicly available summary statistics from GWAS for AD to investigate causal AD. estimated whole-genome sequence data blood brain samples 13,799 individuals Alzheimer's Disease Sequencing Project. Linear Cox proportional hazards models adjusting age, sex, study phase were used assess association with The biomarkers serum metabolites was evaluated Neuroimaging Initiative linear regression. conducted mediation analysis test natural indirect effects change on risk through significantly associated metabolites. MR suggested decreased blood-derived increased (OR = 0.68; P 0.013). Survival showed that higher conversion mild cognitive impairment (HR 0.80; 0.002). identified significant associations FDG-PET (β 0.103; 0.022), amyloid-PET 0.117; 0.034), CSF amyloid-β (Aβ) 42/40 (β=-0.124; 0.017), t-Tau 0.128; 0.015), p-Tau 0.140; 0.008), plasma NFL 0.004) females. Several species, amino acids, biogenic amines mtDNA-CN. Causal analyses about third effect mediated by (P 0.009), this more females < 0.005). Our measured predictive including particularly Further, we illustrate possibly increases dysregulation metabolism inflammation.

Language: Английский

Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging DOI
Domenico Lapenna

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102066 - 102066

Published: Sept. 7, 2023

Language: Английский

Citations

80

The autophagy–NAD axis in longevity and disease DOI Creative Commons

Niall Wilson,

Tetsushi Kataura,

Miriam E. Korsgen

et al.

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(9), P. 788 - 802

Published: March 5, 2023

Autophagy is an intracellular degradation pathway that recycles subcellular components to maintain metabolic homeostasis. NAD essential metabolite participates in energy metabolism and serves as a substrate for series of NAD+-consuming enzymes (NADases), including PARPs SIRTs. Declining levels autophagic activity represent features cellular ageing, consequently enhancing either significantly extends health/lifespan animals normalises cells. Mechanistically, it has been shown NADases can directly regulate autophagy mitochondrial quality control. Conversely, preserve by modulating stress. In this review we highlight the mechanisms underlying bidirectional relationship between autophagy, potential therapeutic targets provides combatting age-related disease promoting longevity.

Language: Английский

Citations

59

Spermidine is essential for fasting-mediated autophagy and longevity DOI Creative Commons
Sebastian J. Hofer, Ioanna Daskalaki, Martina Bergmann

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1571 - 1584

Published: Aug. 8, 2024

Abstract Caloric restriction and intermittent fasting prolong the lifespan healthspan of model organisms improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection reduced incidence cardiovascular neurodegenerative diseases across species borders. Here, we asked whether cellular physiological consequences caloric depend on metabolism. We report that levels increased upon distinct regimens or in yeast, flies, mice volunteers. Genetic pharmacological blockade endogenous synthesis fasting-induced nematodes cells. Furthermore, perturbing pathway vivo abrogated lifespan- healthspan-extending effects, as well cardioprotective anti-arthritic fasting. Mechanistically, mediated these effects via induction hypusination translation regulator eIF5A. In summary, polyamine–hypusination axis emerges a phylogenetically conserved metabolic control hub for fasting-mediated enhancement longevity.

Language: Английский

Citations

43

Aging, cancer, and autophagy: connections and therapeutic perspectives DOI Creative Commons

Begoña Zapatería,

Esperanza Arias

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 28, 2025

Aging and cancer are intricately linked through shared molecular processes that influence both the onset of malignancy progression age-related decline. As organisms age, cellular stress, genomic instability, an accumulation senescent cells create a pro-inflammatory environment conducive to development. Autophagy, process responsible for degrading recycling damaged components, plays pivotal role in this relationship. While autophagy acts as tumor-suppressive mechanism by preventing organelles proteins, often exploit it survive under conditions metabolic stress treatment resistance. The interplay between aging, cancer, reveals key insights into tumorigenesis, senescence, proteostasis dysfunction. This review explores connections these processes, emphasizing potential autophagy-targeted therapies strategies could be further explored aging treatment. Understanding dual roles suppressing promoting offers promising avenues therapeutic interventions aimed at improving outcomes elderly patients while addressing deterioration.

Language: Английский

Citations

4

Targeting Efferocytosis in Inflammaging DOI Creative Commons
Ivan K. H. Poon, Kodi S. Ravichandran

The Annual Review of Pharmacology and Toxicology, Journal Year: 2023, Volume and Issue: 64(1), P. 339 - 357

Published: Aug. 16, 2023

Rapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance tissue homeostasis, resolution inflammation, and repair. However, impaired efferocytosis can result in accumulation cells, subsequently triggering sterile inflammation through release endogenous factors such DNA nuclear proteins from membrane permeabilized dying cells. Here, we review molecular basis three phases that is, detection, uptake, degradation materials phagocytes. We also discuss how defects due to alteration phagocytes contribute low-grade chronic occurs during aging, described inflammaging. Lastly, explore opportunities targeting harnessing efferocytic machinery limit aging-associated inflammatory diseases.

Language: Английский

Citations

30

The obesity-autophagy-cancer axis: Mechanistic insights and therapeutic perspectives DOI Creative Commons
Amir Barzegar Behrooz, Marco Cordani, Alessandra Fiore

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 99, P. 24 - 44

Published: Feb. 1, 2024

Autophagy, a self-degradative process vital for cellular homeostasis, plays significant role in adipose tissue metabolism and tumorigenesis. This review aims to elucidate the complex interplay between autophagy, obesity, cancer development, with specific emphasis on how obesity-driven changes affect regulation of autophagy subsequent implications risk. The burgeoning epidemic obesity underscores relevance this research, particularly given established links various cancers. Our exploration delves into hormonal influence, notably INS (insulin) LEP (leptin), interactions. Further, we draw attention latest findings molecular factors linking cancer, including changes, altered metabolism, secretory autophagy. We posit that targeting modulation may offer potent therapeutic approach obesity-associated pointing promising advancements nanocarrier-based targeted therapies modulation. However, also recognize challenges inherent these approaches, concerning their precision, control, dual roles can play cancer. Future research directions include identifying novel biomarkers, refining therapies, harmonizing approaches precision medicine principles, thereby contributing more personalized, effective treatment paradigm obesity-mediated

Language: Английский

Citations

18

The crosstalk between metabolism and translation DOI
Stefano Biffo, Davide Ruggero, Massimo Santoro

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(9), P. 1945 - 1962

Published: Sept. 1, 2024

Language: Английский

Citations

16

Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease DOI Open Access
Sumit Kumar Anand, Theresea-Anne Governale, Xiangyu Zhang

et al.

American Journal Of Pathology, Journal Year: 2024, Volume and Issue: 194(4), P. 510 - 524

Published: Jan. 1, 2024

Language: Английский

Citations

12

Long-distance microbial mechanisms impacting cancer immunosurveillance DOI
Laurence Zitvogel, Marine Fidelle, Guido Kroemer

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(9), P. 2013 - 2029

Published: Aug. 15, 2024

Language: Английский

Citations

11

Difference in gut microbial dysbiotic patterns between body-first and brain-first Parkinson's disease DOI Creative Commons
Don Gueu Park, Woorim Kang,

In-Ja Shin

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 201, P. 106655 - 106655

Published: Aug. 30, 2024

This study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes Parkinson's disease (PD). could illuminate the unique pathogenic mechanisms within these subtypes.

Language: Английский

Citations

9