Age-Associated Decrease in Proteasome Content and Activities in Human Dermal Fibroblasts: Restoration of Normal Level of Proteasome Subunits Reduces Aging Markers in Fibroblasts From Elderly Persons

Hwang, Jung Sun; Hwang, Jae Sung; Chang, Ih-Seop; Kim, Sujong

doi:10.1093/gerona/62.5.490

Cited by 88 publications

(66 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observed coregulation of b-type subunits has also been confirmed in other cell types, such as the lens epithelial cells (23) or the murine neuroblastoma cells (24), following overexpression of the b 5 subunit. Moreover, it was recently shown that restoration of the normal level of proteasome subunits in aged human fibroblasts reduces the levels of various aging biomarkers (25), thereby confirming our assumption regarding the vital association between optimal proteasome function and retention of cellular homeostasis. Finally, we have recently achieved proteasomal upregulation via overexpression of hUMP1/POMP protein (26).…”

Section: Genetic Activation Of the Proteasomesupporting

confidence: 80%

Proteasome activation as a novel antiaging strategy

Chondrogianni

Gonos

2008

IUBMB Life

View full text Add to dashboard Cite

SummaryHomeostasis is a key feature of cellular lifespan. Maintenance of cellular homeostasis influences the rate of aging and is determined by several factors, including efficient proteolysis of damaged proteins. Protein degradation is predominately catalyzed by the proteasome. Specifically, the proteasome is responsible for cell clearance of abnormal, denatured or in general damaged proteins as well as for the regulated degradation of short-lived proteins. As proteasome has an impaired function during aging, emphasis has been given recently in identifying ways of its activation. A number of studies have shown that the proteasome can be activated by genetic manipulations as well as by factors that affect its conformation and stability. Importantly the developed proteasome activated cell lines exhibit an extended lifespan. This review article discusses in details the various factors that are involved in proteasome biosynthesis and assembly and how they contribute to its activation. Finally as few natural compounds have been identified having proteasome activation properties, we discuss the advantages of this novel antiaging strategy. PROTEASOME, A KEY COMPONENT FOR PROTEIN DEGRADATION AND MAINTENANCE OF CELLULAR HOMEOSTASISHomeostasis is a key feature that determines organismal lifespan. Maintenance of homeostasis is influenced by several intracellular functions, which, in turn, determine the quality and the extent of cellular and organismal lifespan (1). Efficient protein degradation is one of the major factors that contribute to the retention of cellular homeostatic balance.Protein degradation is predominately catalyzed by the proteasome. The proteasome is responsible for cell clearance of abnormal, denatured or in general damaged proteins as well as, for the regulated degradation of short-lived proteins (2, 3). The 20S proteasome, a 700 kDa multisubunit enzyme complex, is a barrel-shape stack of four heptameric rings localized in both cytoplasm and nucleus. The two outer a-subunits rings (a 1-7 ) embrace two central head-to-head oriented rings containing b-subunits (b 1-7 ). The internal chamber that is composed by b-subunits hosts the proteolytic active sites. Three of the b-subunits, b 1 , b 2 , and b 5 , are responsible for the proteasome hydrolyzing activities that cleave peptide bonds on the carboxyl site of acidic (peptidylglutamylpeptide hydrolyzing activity, PGPH), basic (trypsin-like activity, T-L), and hydrophobic (chymotrypsin-like activity, CT-L) amino acids, respectively (3).Capping of each side of 20S particle by 19S regulatory complexes gives rise to 26S proteasome that is responsible for the ATP/ubiquitin-dependent protein degradation. The 19S particle is composed of two subcomplexes, namely the lid and the base. The lid covers the base and it is involved in the recognition and ubiquitin chain processing of substrates before their translocation and degradation. The base is consisted of six ATPase subunits involved in the unfolding and further translocation of the substrate (4). The target pro...

show abstract

Section: Genetic Activation Of the Proteasomesupporting

confidence: 80%

Proteasome activation as a novel antiaging strategy

Chondrogianni

Gonos

2008

IUBMB Life

View full text Add to dashboard Cite

show abstract

“…A decrease in the proteasomal activity has been shown in human tissue for muscle (Ferrington et al, 2005;Husom et al, 2004), lens (Viteri et al, 2004) (but not in the nucleus of the lens, except for cases of cataract-formation (Zetterberg et al, 2003)), lymphocytes and epidermal cells like keratinocytes and fibroblasts (Sitte et al, 2000c,d;Hwang et al, 2007). An intracellular increase of oxidatively modified but not degraded proteins was found, too (Stadtman, 1992).…”

Section: The Proteasomal System and Agingmentioning

confidence: 96%

“…During intrinsic skin aging, lipofuscin, known to be a protein aggregate occurring during time, is also thought to be a reason of proteasome inhibition (Sitte et al, 2000b). Hwang et al (2007) measured proteasome activities and the levels of proteasome subunits in dermal fibroblasts from individuals aged 20-82 years. They showed that proteasome activities changed with age in a biphasic manner, decreasing significantly up to 50 years of age and showing no significant change between 50 and 78 years of age.…”

Section: Intrinsic Skin Agingmentioning

confidence: 99%

The proteasomal system

Jung

Karademir

Grune

2009

Molecular Aspects of Medicine

364

311

View full text Add to dashboard Cite

“…Overexpression of catalytic subunits of the proteasome has demonstrated not only an effective improvement in proteolysis in the cells, but also confer resistance to oxidant-induced damage (186). Further, recent studies have shown that restoration of normal levels of proteasomal subunits and activity are responsible in the reduction of aging biomarkers in a cellular model of senescence (155). Kwak and colleagues have demonstrated that cancer chemopreventatives, such as oltipraz and D3T, are potent inducers of proteasome genes (187).…”

Section: E Induction Of Ups As a Mechanism For Intervention In Immunmentioning

confidence: 99%

Aging and Immune Function: Molecular Mechanisms to Interventions

Ponnappan

2011

Antioxidants & Redox Signaling

290

266

View full text Add to dashboard Cite

The immune system of an organism is an essential component of the defense mechanism aimed at combating pathogenic stress. Age-associated immune dysfunction, also dubbed ''immune senescence,'' manifests as increased susceptibility to infections, increased onset and progression of autoimmune diseases, and onset of neoplasia. Over the years, extensive research has generated consensus in terms of the phenotypic and functional defects within the immune system in various organisms, including humans. Indeed, age-associated alterations such as thymic involution, T cell repertoire skewing, decreased ability to activate naïve T cells and to generate robust memory responses, have been shown to have a causative role in immune decline. Further, understanding the molecular mechanisms underlying the generation of proteotoxic stress, DNA damage response, modulation of ubiquitin proteasome pathway, and regulation of transcription factor NFkB activation, in immune decline, have paved the way to delineating signaling pathways that cross-talk and impact immune senescence. Given the role of the immune system in combating infections, its effectiveness with age may well be a marker of health and a predictor of longevity. It is therefore believed that a better understanding of the mechanisms underlying immune senescence will lead to an effective interventional strategy aimed at improving the health span of individuals. Antioxid. Redox Signal. 14, 1551-1585.

show abstract

Age-Associated Decrease in Proteasome Content and Activities in Human Dermal Fibroblasts: Restoration of Normal Level of Proteasome Subunits Reduces Aging Markers in Fibroblasts From Elderly Persons

Cited by 88 publications

References 23 publications

Proteasome activation as a novel antiaging strategy

Proteasome activation as a novel antiaging strategy

The proteasomal system

Aging and Immune Function: Molecular Mechanisms to Interventions

Contact Info

Product

Resources

About