Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Apr 3

PMID 33809718

Citations 40

Authors

Mengdi Yu

Hongxia Zhang

Brian Wang

Yinuo Zhang

Xiaoying Zheng

Bei Shao

Qichuan Zhuge

Kunlin Jin

Affiliations

Soon will be listed here.

Abstract

Aging is a fundamental biological process accompanied by a general decline in tissue function. Indeed, as the lifespan increases, age-related dysfunction, such as cognitive impairment or dementia, will become a growing public health issue. Aging is also a great risk factor for many age-related diseases. Nowadays, people want not only to live longer but also healthier. Therefore, there is a critical need in understanding the underlying cellular and molecular mechanisms regulating aging that will allow us to modify the aging process for healthy aging and alleviate age-related disease. Here, we reviewed the recent breakthroughs in the mechanistic understanding of biological aging, focusing on the adenosine monophosphate-activated kinase (AMPK), Sirtuin 1 (SIRT1) and mammalian target of rapamycin (mTOR) pathways, which are currently considered critical for aging. We also discussed how these proteins and pathways may potentially interact with each other to regulate aging. We further described how the knowledge of these pathways may lead to new interventions for antiaging and against age-related disease.

Citing Articles

Assessment of the Capability of Mesenchymal Stem Cells and/or Pyrroloquinoline Quinone in Compensating the Age-Related Dysfunctions of AMP-Activated Protein Kinase Pathway in Wistar Rats.

Al Nishilli K, El Zayat E, Abdelgayed S, Hosney M, Hassan N Cell Biochem Biophys. 2025; .

PMID: 40048044 DOI: 10.1007/s12013-025-01693-7.

Prevalence of participation of Brazilian aged people in Advanced Activities of Daily Living and associated factors.

Mazer V, Moreira R, de Lima K, Coriolano M, Silva V Rev Bras Epidemiol. 2024; 27:e240070.

PMID: 39699466 PMC: 11654639. DOI: 10.1590/1980-549720240070.

The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review.

Miceli G, Basso M, Pennacchio A, Cocciola E, Pintus C, Cuffaro M Medicina (Kaunas). 2024; 60(11).

PMID: 39596981 PMC: 11596194. DOI: 10.3390/medicina60111796.

Full-length direct RNA sequencing reveals extensive remodeling of RNA expression, processing and modification in aging Caenorhabditis elegans.

Schiksnis E, Nicastro I, Pasquinelli A Nucleic Acids Res. 2024; 52(22):13896-13913.

PMID: 39558169 PMC: 11662692. DOI: 10.1093/nar/gkae1064.

Elucidation of anti-human melanoma and anti-aging mechanisms of compounds from green seaweed Caulerpa racemosa.

Wicaksono D, Taslim N, Lau V, Syahputra R, Alatas A, Putra P Sci Rep. 2024; 14(1):27534.

PMID: 39528552 PMC: 11555072. DOI: 10.1038/s41598-024-78464-6.

References

Li B, Wu G, Dai W, Wang G, Su H, Shen X . Aescin-induced reactive oxygen species play a pro-survival role in human cancer cells via ATM/AMPK/ULK1-mediated autophagy. Acta Pharmacol Sin. 2018; 39(12):1874-1884. PMC: 6289397. DOI: 10.1038/s41401-018-0047-1. View

Kueck A, Opipari Jr A, Griffith K, Tan L, Choi M, Huang J . Resveratrol inhibits glucose metabolism in human ovarian cancer cells. Gynecol Oncol. 2007; 107(3):450-7. DOI: 10.1016/j.ygyno.2007.07.065. View

Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L . The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012; 483(7388):218-21. DOI: 10.1038/nature10815. View

Escande C, Nin V, Price N, Capellini V, Gomes A, Barbosa M . Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes. 2012; 62(4):1084-93. PMC: 3609577. DOI: 10.2337/db12-1139. View

Zainabadi K, Liu C, Caldwell A, Guarente L . SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis. PLoS One. 2017; 12(9):e0185236. PMC: 5609767. DOI: 10.1371/journal.pone.0185236. View

Chellappa K, Brinkman J, Mukherjee S, Morrison M, Alotaibi M, Carbajal K . Hypothalamic mTORC2 is essential for metabolic health and longevity. Aging Cell. 2019; 18(5):e13014. PMC: 6718533. DOI: 10.1111/acel.13014. View

Camacho-Pereira J, Tarrago M, Chini C, Nin V, Escande C, Warner G . CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016; 23(6):1127-1139. PMC: 4911708. DOI: 10.1016/j.cmet.2016.05.006. View

Soukas A, Hao H, Wu L . Metformin as Anti-Aging Therapy: Is It for Everyone?. Trends Endocrinol Metab. 2019; 30(10):745-755. PMC: 6779524. DOI: 10.1016/j.tem.2019.07.015. View

Yu W, Qin J, Chen C, Fu Y, Wang W . Moderate calorie restriction attenuates age‑associated alterations and improves cardiac function by increasing SIRT1 and SIRT3 expression. Mol Med Rep. 2018; 18(4):4087-4094. DOI: 10.3892/mmr.2018.9390. View

10.

Kapahi P, Zid B, Harper T, Koslover D, Sapin V, Benzer S . Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004; 14(10):885-90. PMC: 2754830. DOI: 10.1016/j.cub.2004.03.059. View

11.

Ramos F, Chen S, Garelick M, Dai D, Liao C, Schreiber K . Rapamycin reverses elevated mTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletal muscle function, and extends survival. Sci Transl Med. 2012; 4(144):144ra103. PMC: 3613228. DOI: 10.1126/scitranslmed.3003802. View

12.

Wang J, Song Y, Li H, Shen Q, Shen J, An X . Exacerbated cardiac fibrosis induced by β-adrenergic activation in old mice due to decreased AMPK activity. Clin Exp Pharmacol Physiol. 2016; 43(11):1029-1037. DOI: 10.1111/1440-1681.12622. View

13.

Fulco M, Cen Y, Zhao P, Hoffman E, McBurney M, Sauve A . Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell. 2008; 14(5):661-73. PMC: 2431467. DOI: 10.1016/j.devcel.2008.02.004. View

14.

Ido Y, Duranton A, Lan F, Weikel K, Breton L, Ruderman N . Resveratrol prevents oxidative stress-induced senescence and proliferative dysfunction by activating the AMPK-FOXO3 cascade in cultured primary human keratinocytes. PLoS One. 2015; 10(2):e0115341. PMC: 4315597. DOI: 10.1371/journal.pone.0115341. View

15.

Kaeberlein M, Powers 3rd R, Steffen K, Westman E, Hu D, Dang N . Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science. 2005; 310(5751):1193-6. DOI: 10.1126/science.1115535. View

16.

Liu Y, Weng W, Gao R, Liu Y . New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach. Oxid Med Cell Longev. 2020; 2019:4598167. PMC: 6930799. DOI: 10.1155/2019/4598167. View

17.

Harman D . Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956; 11(3):298-300. DOI: 10.1093/geronj/11.3.298. View

18.

Mitsuhashi K, Senmaru T, Fukuda T, Yamazaki M, Shinomiya K, Ueno M . Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes. Endocrine. 2015; 51(1):174-84. DOI: 10.1007/s12020-015-0666-y. View

19.

Kaisar M, Villalba H, Prasad S, Liles T, Sifat A, Sajja R . Offsetting the impact of smoking and e-cigarette vaping on the cerebrovascular system and stroke injury: Is Metformin a viable countermeasure?. Redox Biol. 2017; 13:353-362. PMC: 5480985. DOI: 10.1016/j.redox.2017.06.006. View

20.

Tulsian R, Velingkaar N, Kondratov R . Caloric restriction effects on liver mTOR signaling are time-of-day dependent. Aging (Albany NY). 2018; 10(7):1640-1648. PMC: 6075448. DOI: 10.18632/aging.101498. View