» Articles » PMID: 30458935

Targeting Autophagy in Aging and Aging-Related Cardiovascular Diseases

Overview
Specialty Pharmacology
Date 2018 Nov 22
PMID 30458935
Citations 126
Authors
Affiliations
Soon will be listed here.
Abstract

Aging, an irreversible biological process, serves as an independent risk factor for chronic disease including cancer, pulmonary, neurodegenerative, and cardiovascular diseases. In particular, high morbidity and mortality have been associated with cardiovascular aging, but effective clinical therapeutic remedies are suboptimal for the ever-rising aging population. Recent evidence suggests a unique role for aberrant aggregate clearance and the protein quality control machinery - the process of autophagy - in shortened lifespan, compromised healthspan, and the onset and development of aging-associated cardiovascular diseases. Autophagy degrades and removes long-lived or damaged cellular organelles and proteins, the functions of which decline with advanced aging. Induction of autophagy using rapamycin, resveratrol, nicotinamide derivatives, metformin, urolithin A, or spermidine delays aging, prolongs lifespan, and improves cardiovascular function in aging. Given the ever-rising human lifespan and aging population as well as the prevalence of cardiovascular disease provoked by increased age, it is pertinent to understand the contribution and underlying mechanisms of autophagy and organelle-selective autophagy (e.g., mitophagy) in the regulation of lifespan, healthspan, and cardiovascular aging. Here we dissect the mechanism of action for autophagy failure in aging and discuss the potential rationale of targeting autophagy using pharmacological agents as new avenues in the combating of biological and cardiovascular aging.

Citing Articles

Transcriptomic profiles of single-cell autophagy-related genes (ATGs) in lung diseases.

Liu X, Zhang L, Li L, Hou J, Qian M, Zheng N Cell Biol Toxicol. 2025; 41(1):40.

PMID: 39920481 PMC: 11805875. DOI: 10.1007/s10565-025-09990-w.


Inflammation in atherosclerosis: pathophysiology and mechanisms.

Ajoolabady A, Pratico D, Lin L, Mantzoros C, Bahijri S, Tuomilehto J Cell Death Dis. 2024; 15(11):817.

PMID: 39528464 PMC: 11555284. DOI: 10.1038/s41419-024-07166-8.


Body Roundness Index Trajectories and the Incidence of Cardiovascular Disease: Evidence From the China Health and Retirement Longitudinal Study.

Yang M, Liu J, Shen Q, Chen H, Liu Y, Wang N J Am Heart Assoc. 2024; 13(19):e034768.

PMID: 39319466 PMC: 11681446. DOI: 10.1161/JAHA.124.034768.


LPI-GPR55 promotes endothelial cell activation and inhibits autophagy through inducing LINC01235 expression.

He X, Zhao X, Wang H Ann Med. 2024; 56(1):2407525.

PMID: 39316662 PMC: 11423533. DOI: 10.1080/07853890.2024.2407525.


Bioinformatics Identification and Experimental Verification of Disulfidptosis-Related Genes in the Progression of Osteoarthritis.

Cao S, Wei Y, Yue Y, Wang D, Xiong A, Yang J Biomedicines. 2024; 12(8).

PMID: 39200304 PMC: 11351109. DOI: 10.3390/biomedicines12081840.


References
1.
Yang S, Long L, Li D, Zhang J, Jin S, Wang F . β-Guanidinopropionic acid extends the lifespan of Drosophila melanogaster via an AMP-activated protein kinase-dependent increase in autophagy. Aging Cell. 2015; 14(6):1024-33. PMC: 4693457. DOI: 10.1111/acel.12371. View

2.
Lesniewski L, Seals D, Walker A, Henson G, Blimline M, Trott D . Dietary rapamycin supplementation reverses age-related vascular dysfunction and oxidative stress, while modulating nutrient-sensing, cell cycle, and senescence pathways. Aging Cell. 2016; 16(1):17-26. PMC: 5242306. DOI: 10.1111/acel.12524. View

3.
Turdi S, Fan X, Li J, Zhao J, Huff A, Du M . AMP-activated protein kinase deficiency exacerbates aging-induced myocardial contractile dysfunction. Aging Cell. 2010; 9(4):592-606. PMC: 2910211. DOI: 10.1111/j.1474-9726.2010.00586.x. View

4.
Shirakabe A, Ikeda Y, Sciarretta S, Zablocki D, Sadoshima J . Aging and Autophagy in the Heart. Circ Res. 2016; 118(10):1563-76. PMC: 4869999. DOI: 10.1161/CIRCRESAHA.116.307474. View

5.
Ren J, Yang L, Zhu L, Xu X, Ceylan A, Guo W . Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling: role of Sirt1-mediated autophagy regulation. Aging Cell. 2017; 16(5):976-987. PMC: 5595687. DOI: 10.1111/acel.12616. View