Abstract:
:Lysosomes are involved in degrading and recycling cellular ingredients, and their disruption with age may contribute to amyloidogenesis, paired helical filaments (PHFs), and α-synuclein and mutant huntingtin aggregation. Lysosomal cathepsins are upregulated by accumulating proteins and more so by the modulator Z-Phe-Ala-diazomethylketone (PADK). Such positive modulators of the lysosomal system have been studied in the well-characterized hippocampal slice model of protein accumulation that exhibits the pathogenic cascade of tau aggregation, tubulin breakdown, microtubule destabilization, transport failure, and synaptic decline. Active cathepsins were upregulated by PADK; Rab proteins were modified as well, indicating enhanced trafficking, whereas lysosome-associated membrane protein and proteasome markers were unchanged. Lysosomal modulation reduced the pre-existing PHF deposits, restored tubulin structure and transport, and recovered synaptic components. Further proof-of-principle studies used Alzheimer disease mouse models. It was recently reported that systemic PADK administration caused dramatic increases in cathepsin B protein and activity levels, whereas neprilysin, insulin-degrading enzyme, α-secretase, and β-secretase were unaffected by PADK. In the transgenic models, PADK treatment resulted in clearance of intracellular amyloid beta (Aβ) peptide and concomitant reduction of extracellular deposits. Production of the less pathogenic Aβ(1-38) peptide corresponded with decreased levels of Aβ(1-42), supporting the lysosome's antiamyloidogenic role through intracellular truncation. Amelioration of synaptic and behavioral deficits also indicates a neuroprotective function of the lysosomal system, identifying lysosomal modulation as an avenue for disease-modifying therapies. From the in vitro and in vivo findings, unique lysosomal modulators represent a minimally invasive, pharmacologically controlled strategy against protein accumulation disorders to enhance protein clearance, promote synaptic integrity, and slow the progression of dementia.
journal_name
Rejuvenation Resjournal_title
Rejuvenation researchauthors
Bahr BA,Wisniewski ML,Butler Ddoi
10.1089/rej.2011.1282subject
Has Abstractpub_date
2012-04-01 00:00:00pages
189-97issue
2eissn
1549-1684issn
1557-8577journal_volume
15pub_type
杂志文章abstract::We have reported the isolation of a unique subpopulation of human stromal cells from bone marrow termed marrow-isolated adult multilineage inducible (MIAMI) cells. The expression of embryonic stem cell markers SSEA-4, Oct-4, Rex-1, and telomerase reverse transcriptase indicates the developmentally immature status of t...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2006.9.10
更新日期:2006-04-01 00:00:00
abstract::Prunella vulgaris L., a well-known traditional Chinese herbal medicine, has anti-inflammatory and antioxidant activities. In the present study, the underlying molecular mechanisms of the protective effect of P. vulgaris extract (PVE) were investigated in UVB-irradiated normal human dermal fibroblasts (NHDFs). The mRNA...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2017.1971
更新日期:2018-08-01 00:00:00
abstract::Human growth hormone-2 (GH-2) is a 191-amino-acid protein also known as human placental hormone. During pregnancy, continuous secretion of GH-2 appears to have important implications for physiological adjustment to gestation, especially in controlling levels of maternal insulin-like growth factor 1. To compare the phy...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2014.1594
更新日期:2015-02-01 00:00:00
abstract::This study aimed at comparing the effects of three chair-based exercise programs on people older than 80 years. Thirty-six participants (87.91 ± 4.70 years) were randomly allocated to an aerobic, muscular resistance, or joint mobility exercise program. The participants exercised 3 days per week during 3 months. A hand...
journal_title:Rejuvenation research
pub_type: 杂志文章,随机对照试验
doi:10.1089/rej.2017.1924
更新日期:2017-10-01 00:00:00
abstract::The aim of the current study was to develop fitness standards associated with maintaining physical capacity in older adults at two different levels-that needed for advanced functioning and that needed for maintaining moderate (independent) functional ability. This was a cross-sectional study of 406 Chilean adults aged...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2016.1913
更新日期:2017-12-01 00:00:00
abstract::Maillard reactions are an unavoidable feature of life that appear to be damaging to cell and organisms. Consequently, all living systems must have ways to protect themselves against this process. As of 2012, several such defense mechanisms have been identified. They are all enzymatic and were found in mesophilic organ...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2012.1401
更新日期:2013-08-01 00:00:00
abstract::Advanced glycation end products are the results of a series of chemical reactions collectively known as the Maillard reaction, or nonenzymatic glycation, and sometimes cross-link proteins, thereby impairing their normal function. Glucosepane is the most abundant protein cross-link found in vivo so far and mainly has b...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2009.0846
更新日期:2009-04-01 00:00:00
abstract::Mitochondria play a central role in cellular physiology. Besides their classic function of energy metabolism, mitochondria are involved in multiple cell functions, including energy distribution through the cell, energy/heat modulation, regulation of reactive oxygen species (ROS), calcium homeostasis, and control of ap...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2015.1704
更新日期:2016-02-01 00:00:00
abstract::The full power of gene modification in higher eukaryotes, including its potential to correct disease-causing mutations, has so far been limited by its low efficiency. Now that power looks set to be released through the use of customized endonuclease "hands," DNA-binding zinc fingers linked to nuclease "thumbs," capabl...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2005.8.211
更新日期:2005-01-01 00:00:00
abstract::The release of mitochondrial cytochrome c followed by activation of caspase cascade has been reported with aging in various tissues, whereas little is known about the caspase-independent pathway involved in mitochondrial dysfunction. To determine the functional impact of cytochrome c loss on mitochondrial respiratory ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2007.0541
更新日期:2007-09-01 00:00:00
abstract::Homocysteine (Hcy) could induce amyloid β (Aβ) accumulation, synaptic dysfunction, and memory impairment as seen in Alzheimer disease (AD), the most prevalent neurodegenerative disorder, which affects more than 25 million people worldwide. Here we investigated the protective effect of hydroxysafflor yellow A (HSYA) on...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2013.1451
更新日期:2013-12-01 00:00:00
abstract::Pursuance of longevity is not only combating decrepitude but it is also extending the health span; otherwise longevity would result in a universal medical and social burden. As revealed by the literature, the attainment of a healthy life could be impacted by the social milieu. An inquiry of this kind could hardly be s...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2010.1071
更新日期:2011-02-01 00:00:00
abstract::Older patients often suffer from multiple co-morbid conditions. Few co-morbidity indices are valid and reliable in elderly patients and comparison between them is rare. Our objective was to compare the performance, relevance, and abilities of six widely used and validated co-morbidity indices--the Charlson Cumulative ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2010.1037
更新日期:2010-12-01 00:00:00
abstract::Baicalein is a flavonoid isolated from the roots of Scutellaria baicalensis Georgi. This study aimed to ascertain the effects and potential underlying mechanisms of baicalein in d-galactose (d-gal)-induced aging rat model by integration of behavior examination, biochemical detection, and 1H nuclear magnetic resonance ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2017.1919
更新日期:2017-12-01 00:00:00
abstract::Astaxanthin (AST), a xanthophyll belonging to the family of carotenoids, is a potent antioxidant. The effect of AST on longevity and its physiological and molecular mechanism are still unclear. In this study, we proved that AST could prolong the life span of Caenorhabditis elegans. To uncover whether AST could delay a...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2020.2355
更新日期:2020-11-30 00:00:00
abstract::Decades of studies of candidate genes show their complex role in aging-related traits. We focus on apolipoprotein E e2/3/4 polymorphism and ages at onset of cardiovascular diseases (CVD) and cancer in the parental and offspring generations of the Framingham Heart Study participants to gain insights on the role of age ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2012.1362
更新日期:2013-02-01 00:00:00
abstract::To determine the prognostic value of frailty and comorbidity for outdoor mobility loss and mortality in the elderly. The retrospective study was conducted among outpatients aged ≥60 years. Patients with ≥3 chronic illnesses were treated by doctors who had undergone a 72-hour geriatric training. The outdoor low-mobilit...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2019.2289
更新日期:2020-07-14 00:00:00
abstract::Alzheimer's disease (AD) is a common form of dementia and amyloid-β peptide (Aβ) aggregation is considered to be one of its main causes. Paeoniflorin has been previously shown to attenuate cognitive damage inflicted by exogenous Aβ protein. Using transgenic Caenorhabditis elegans models expressing human Aβ1-42, we dem...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2017.1966
更新日期:2018-08-01 00:00:00
abstract::The progeroid Werner's syndrome (WS) represents the best current model of human aging. It is caused by loss of the WRN helicase/exonuclease, resulting in high levels of replication fork stalling and genomic instability. Current models suggest that characteristic WS phenotypes of poor S phase progression, low prolifera...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2006.0503
更新日期:2007-03-01 00:00:00
abstract::Availability of reliable prognostic biomarkers that are also able to monitor preventive/therapeutic interventions in patients with mild cognitive impairment (MCI) is crucial. Cerebral brain-derived neurotrophic factor (BDNF) alterations were evidenced in Alzheimer's disease, but the value of blood BDNF in MCI is uncle...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2020.2307
更新日期:2020-10-01 00:00:00
abstract::The human mitochondrion contains a small circular genome that codes for 13 proteins, 22 tRNAs, and 2 rRNAs. The proteins are all inner membrane bound components of complexes involved in the electron transport system and ATP formation. Mutations to any of the 13 proteins affect cellular behavior because energy producti...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2006.9.182
更新日期:2006-07-01 00:00:00
abstract::Aristotle described the study of politics as an "architectonic" science that aspires to bring together insights from different fields of scientific inquiry to ensure that citizens have the opportunities to flourish. To meet the health and economic challenges of aging populations, we must revive this Aristotelian visio...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2010.1023
更新日期:2010-10-01 00:00:00
abstract::The United States has the most expensive healthcare system worldwide. Yet measures of health span and life expectancy are well below the major industrialized nations. With the U.S. population aged 65 years and older projected to double by mid-century, a healthcare crisis is looming. Within this context, huge interest ...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2018.2088
更新日期:2018-06-01 00:00:00
abstract::The mouse Mus musculus chromosomes are all acrocentric; each centromere (CEN) is adjacent to a telomere. The aim of the current work is to find out if at least half of the mouse telomeres (Tel) always follow satellite DNA sequences and if membrane telomere binding protein TRF2/MTBP is always in association with the Te...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2006.9.391
更新日期:2006-10-01 00:00:00
abstract::Theses reviewed in this issue include "Downregulation of the Apelinergic Axis Accelerates Aging, Whereas Its Systemic Restoration Improves the Mammalian Healthspan," "Intracellular Delivery of Exogenous Molecules Via an Ultrahigh Throughput Mechanoporation Microdevice," "Intrinsic and Extrinsic Drivers of Treg Fragili...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2019.2248
更新日期:2019-08-01 00:00:00
abstract::The senescence of the immune system contributes considerably to the age-related diseases that are the main causes of death after the age of 65. In this study, we present an appealing option for the prevention of immune senescence and slowing or reversing the aging process, which can be achieved by heterochronous autol...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2018.2164
更新日期:2020-04-01 00:00:00
abstract::This review discusses the role of estrogens as pro- or antiinflammatory players in immune-inflammatory responses. In particular, their role in Alzheimer's disease (AD), an example of immune-inflammatory disease, is discussed briefly. AD is a progressive neurodegenerative disease, which in Western societies accounts fo...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/rej.2009.0942
更新日期:2010-04-01 00:00:00
abstract::Osteoarthritis is the most common disabling condition of humans in the western world. It has been known for a very long time that aging is the most prominent risk factor for the initiation and progression of the disease, but the explanations for this phenomenon have changed over time. The most longstanding theory is t...
journal_title:Rejuvenation research
pub_type: 杂志文章,评审
doi:10.1089/1549168041552964
更新日期:2004-07-01 00:00:00
abstract:OBJECTIVE:This study examined the impact of estrogen replacement therapy with spirometry on pulmonary function in surgically castrated (salpingo-oophorectomy) postmenopausal women with genital prolapse. METHODS:The study included 60 postmenopausal women with pelvic organ prolapse. The study received institutional Ethi...
journal_title:Rejuvenation research
pub_type: 杂志文章,随机对照试验
doi:10.1089/rej.2012.1337
更新日期:2012-12-01 00:00:00
abstract::A hypothetical mechanism of 14C-generated influence on a person's rate of aging is offered. The mathematical description and the following approbation of the radiocarbon mechanism of aging made it possible to coordinate the Gompertz and Strehler-Mildvan laws and predict the existence of one more, till-now unknown, int...
journal_title:Rejuvenation research
pub_type: 杂志文章
doi:10.1089/rej.2006.9.309
更新日期:2006-07-01 00:00:00