Abstract
Autophagy is a conserved process that degrades intracellular components through lysosomes, thereby maintaining energy homeostasis and renewal of organelles. Mounting evidence indicates that autophagy plays a key role in aging and aging-related diseases. Enhanced autophagy can delay aging and prolong life span. The absence of autophagy leads to the accumulation of mutant and misfolded proteins in the cell, which is the basis for the emergence and development of neurodegenerative diseases and other aging-related diseases. It will be of importance to develop approaches to extend the lifespan and improve the health of elderly individuals through the modulation of autophagy.
Keywords
- Autophagy
- Aging
- Longevity
This is a preview of subscription content, access via your institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAbbreviations
- CMA:
-
Chaperone-mediated autophagy
- FOXO3a:
-
Forkhead transcription factor
- HSP70:
-
Heat shock protein 70
- IGF-1:
-
Insulin-like growth factor 1
- LAMP2a:
-
Lysosome-associated membrane protein type 2a
- LC3:
-
Microtubule-associated protein 1 light chain 3
- Nrf2:
-
NF-related nuclear factor
- SAMP8:
-
Senescence-accelerated mouse P8
- TOR:
-
Target of rapamycin
- TSC1:
-
Tuberous sclerosis complex 1
- ULK1:
-
Unc-51-like autophagy activating kinase 1
References
Avet-Rochex A, Carvajal N, Christoforou CP, Yeung K, Maierbrugger KT, Hobbs C, Lalli G, Cagin U, Plachot C, McNeill H, Bateman JM (2014) Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control. PLoS Genet 10:e1004624
Crews L, Spencer B, Desplats P, Patrick C, Paulino A, Rockenstein E, Hansen L, Adame A, Galasko D, Masliah E (2010) Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy. PLoS ONE 5:e9313
Cuervo AM, Wong E (2014) Chaperone-mediated autophagy: roles in disease and aging. Cell Res 24:92–104
de Cabo R, Carmona-Gutierrez D, Bernier M, Hall MN, Madeo F (2014) The search for antiaging interventions: from elixirs to fasting regimens. Cell 157:1515–1526
Garcia-Prat L, Munoz-Canoves P, Martinez-Vicente M (2016) Dysfunctional autophagy is a driver of muscle stem cell functional decline with aging. Autophagy 12:612–613
Guarente L (2007) Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol 72:483–488
Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395
Italiano A, Chen CL, Thomas R, Breen M, Bonnet F, Sevenet N, Longy M, Maki RG, Coindre JM, Antonescu CR (2012) Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas: a pattern distinct from other sarcomas with complex genomics. Cancer 118:5878–5887
Kamada Y (2010) Prime-numbered Atg proteins act at the primary step in autophagy: unphosphorylatable Atg13 can induce autophagy without TOR inactivation. Autophagy 6:415–416
Leidal AM, Levine B, Debnath J (2018) Autophagy and the cell biology of age-related disease. Nat Cell Biol 20:1338–1348
Liu S, Lu B (2010) Reduction of protein translation and activation of autophagy protect against PINK1 pathogenesis in Drosophila melanogaster. PLoS Genet 6:e1001237
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217
Luo Y, Hartford SA, Zeng R, Southard TL, Shima N, Schimenti JC (2014) Hypersensitivity of primordial germ cells to compromised replication-associated DNA repair involves ATM-p53-p21 signaling. PLoS Genet 10:e1004471
Ma Q, Qiang J, Gu P, Wang Y, Geng Y, Wang M (2011) Age-related autophagy alterations in the brain of senescence accelerated mouse prone 8 (SAMP8) mice. Exp Gerontol 46:533–541
Ma Y, Qi M, An Y, Zhang L, Yang R, Doro DH, Liu W, Jin Y (2018) Autophagy controls mesenchymal stem cell properties and senescence during bone aging. Aging Cell 17
Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183:795–803
Owusu-Ansah E, Song W, Perrimon N (2013) Muscle mitohormesis promotes longevity via systemic repression of insulin signaling. Cell 155:699–712
Radpour R, Barekati Z, Haghighi MM, Kohler C, Asadollahi R, Torbati PM, Holzgreve W, Zhong XY (2010) Correlation of telomere length shortening with promoter methylation profile of p16p16/Rb and p53/p21 pathways in breast cancer. Mod Pathol 23:763–772
Ryu D, Mouchiroud L, Andreux PA, Katsyuba E, Moullan N, Nicolet-Dit-Felix AA, Williams EG, Jha P, Lo Sasso G, Huzard D, Aebischer P, Sandi C, Rinsch C, Auwerx J (2016) Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med 22:879–88
Sahin E, Depinho RA (2012) Axis of ageing: telomeres, p53 and mitochondria. Nat Rev Mol Cell Biol 13:397–404
Saini N, Oelhafen S, Hua H, Georgiev O, Schaffner W, Bueler H (2010) Extended lifespan of Drosophila parkin mutants through sequestration of redox-active metals and enhancement of anti-oxidative pathways. Neurobiol Dis 40:82–92
Wang L, Sesso HD, Glynn RJ, Christen WG, Bubes V, Manson JE, Buring JE, Gaziano JM (2014) Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians’ Health Study II randomized trial. Am J Clin Nutr 100:915–923
Weatherill DB, Dyer J, Sossin WS (2010) Ribosomal protein S6 kinase is a critical downstream effector of the target of rapamycin complex 1 for long-term facilitation in Aplysia. J Biol Chem 285:12255–12267
Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 14:959–965
Ziv E, Hu D (2011) Genetic variation in insulin/IGF-1 signaling pathways and longevity. Ageing Res Rev 10:201–204
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Science Press and Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Luo, L., Qin, ZH. (2019). Autophagy, Aging, and Longevity. In: Qin, ZH. (eds) Autophagy: Biology and Diseases. Advances in Experimental Medicine and Biology, vol 1206. Springer, Singapore. https://doi.org/10.1007/978-981-15-0602-4_24
Download citation
DOI: https://doi.org/10.1007/978-981-15-0602-4_24
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-0601-7
Online ISBN: 978-981-15-0602-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)