Hormone-brain-aging relationships, broadly reactive with imidazole-containing dipeptides: targeting of telomere attrition as an aging biomarker and dynamic telomerase activity flirting

2015 ◽  
Vol 26 (2) ◽  
Author(s):  
Mark A. Babizhayev ◽  
Khava S. Vishnyakova ◽  
Yegor E. Yegorov
Keyword(s):  
Healthy Aging ◽  
Brain Aging ◽  
The United States ◽  
Telomerase Activity ◽  
Therapeutic Drug ◽  
Physiological Control ◽  
Telomere Shortening ◽  
Therapeutic Concept ◽  
Telomere Attrition ◽  
Age Related

AbstractIt has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, and telomere length (TL) may be an informative biomarker of healthy aging. Hormone-brain-aging behavior-modulated telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state, and these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. We raise and support a therapeutic concept of using nonhydrolyzed forms of naturally occurring neuron-specific imidazole dipeptide-based compounds carnosine and carcinine, making it clinically possible that slowing down the rate of telomere shortening could slow down the human aging process in specific tissues where proliferative senescence is known to occur, with the demonstrated evidence of telomere shortening that appeared to be a hallmark of oxidative stress and disease. Carnosine released from skeletal muscle during exercise may be transported into the hypothalamic tuberomammillary nucleus (TMN) histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and hormone-like antiaging physiological function. The preliminary longitudinal studies of elderly individuals suggest that longer telomeres are associated with better survival, and an advanced oral nutritional support with nonhydrolyzed carnosine (or carcinine and patented compositions thereof) is a useful therapeutic tool for a critical TL maintenance that may fundamentally be applied in the treatment of age-related sight-threatening eye disorders, prolonged life expectancy, increased survival and chronological age of an organism in health control, smoking behavior, and disease.  “Our pleasures were simple—they included survival.”   —Dwight D. Eisenhower, 34th President of the United States, 1953–1961

scholarly journals The Use of Natural Agents to Counteract Telomere Shortening: Effects of a Multi-Component Extract of Astragalus mongholicus Bunge and Danazol

Biomedicines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 31 ◽  
Author(s):  
Isabelle Guinobert ◽  
Claude Blondeau ◽  
Bruno Colicchio ◽  
Noufissa Oudrhiri ◽  
Alain Dieterlen ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Telomerase Activity ◽  
Peripheral Blood Lymphocytes ◽  
Root Extract ◽  
Telomere Shortening ◽  
Patients With Cancer ◽  
Natural Agents ◽  
Age Related ◽  
Healthy Donors ◽  
Aging People

A link between telomere shortening and oxidative stress was found in aging people and patients with cancer or inflammatory diseases. Extracts of Astragalus spp. are known to stimulate telomerase activity, thereby compensating telomere shortening. We characterized a multi-component hydroethanolic root extract (HRE) of Astragalus mongholicus Bunge and assessed its effects on telomeres compared to those of danazol. Astragalosides I to IV, flavonoids, amino acids and sugars were detected in the HRE. Samples of peripheral blood lymphocytes with short telomeres from 18 healthy donors (mean age 63.5 years; range 32–86 years) were exposed to a single dose of 1 µg/mL HRE or danazol for three days. Telomere length and telomerase expression were then measured. Significant elongation of telomeres associated to a less toxicity was observed in lymphocytes from 13/18 donors following HRE treatment (0.54 kb (0.15–2.06 kb)) and in those from 9/18 donors after danazol treatment (0.95 kb (0.06–2.06 kb)). The rate of cells with short telomeres (<3 kb) decreased in lymphocytes from all donors after exposure to either HRE or danazol, telomere elongation being telomerase-dependent. These findings suggest that the HRE could be used for the management of age-related diseases.

scholarly journals Update on the NAS-NRC Twin Registry

2006 ◽  
Vol 9 (6) ◽  
pp. 985-987 ◽  
Author(s):  
William F. Page
Keyword(s):  
Risk Factor ◽  
Healthy Aging ◽  
Morphological Changes ◽  
White Male ◽  
National Research Council ◽  
The United States ◽  
Age Related Macular Degeneration ◽  
Aging Brain ◽  
Twin Registry ◽  
Age Related

AbstractThe National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the United States. It consists of 15,924 white male twin pairs born in the years 1917 to 1927 (inclusive), both of whom served in the armed forces, mostly during World War II. This article updates activity in this registry since the earlier 2002 article in Twin Research. The results of clinically based studies on dementia, Parkinson's disease, age-related macular degeneration, and primary osteoarthritis were published, as well as articles based on previously collected questionnaire data on chronic fatigue syndrome, functional limitations, and healthy aging. In addition, risk factor studies are being planned to merge clinical data with earlier collected risk factor data from questionnaires. Examination data from the subset of National Heart, Lung, and Blood Institute (NHLBI) twins resulted in a number of articles, including the relationship of endogenous sex hormones to coronary heart disease and morphological changes in aging brain structures. The NEO Five-Factor Personality Inventory (a paper-and-pencil self-administered questionnaire) has been fielded for the first time. A push to consolidate the various data holdings of the registry is being made.

scholarly journals CHILDHOOD SOCIOECONOMIC STATUS AND SENSE OF CONTROL OVER COGNITIVE AGING: DO GENES MODERATE?

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S881-S881
Author(s):  
Addam S Reynolds ◽  
Emily Greenfield
Keyword(s):  
Socioeconomic Status ◽  
Cognitive Aging ◽  
Early Life ◽  
Parental Education ◽  
Protective Factor ◽  
Brain Aging ◽  
The United States ◽  
Environment Interaction ◽  
Sense Of Control ◽  
Age Related

Abstract Individuals who lack a sense of control over cognitive aging (SOC-CA) believe little can be done to optimize their cognitive functioning. While prior research indicates that higher SOC-CA is a protective factor against age-related cognitive decline, few studies have examined predictors of change in SOC-CA. To address this gap, we used data from the Midlife in the United States (MIDUS) study. Guided by prior research on linkages between socioeconomic status (SES) and control beliefs, we examined childhood SES as an early life course influence on changes in SOC-CA. The analytic sample consisted of 663 White participants, ages 34 to 81, who were interviewed in 2004 and approximately nine years later. SOC-CA was measured by using three items from the Personality in Aging Context scale, and childhood SES encompassed retrospective reports of parental education and occupational status. A hierarchical linear model was estimated, which modeled SOC-CA at baseline, as well as change over the study period, controlling for gender, age, ancestry, and adult SES. While childhood SES was not associated with SOC-CA at baseline nor over time, a statistically significant gene-environment interaction was found over the 9-year study period. Specifically, participants who scored high on a polygenetic measure for cognitive ability and reported high childhood SES demonstrated a faster rate of decline in SOC-CA. These findings indicate that inter-individual differences stemming from early life influence people’s SOC-CA as they age. Overall, results suggest the importance of subgroup differences within efforts to engage individuals in preventive measures to optimize healthy brain aging.

scholarly journals PML is required for telomere stability in non-neoplastic human cells

Oncogene ◽  
2015 ◽  
Vol 35 (14) ◽  
pp. 1811-1821 ◽  
Author(s):  
M Marchesini ◽  
R Matocci ◽  
L Tasselli ◽  
V Cambiaghi ◽  
A Orleth ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
Human Fibroblasts ◽  
Telomerase Activity ◽  
Telomere Shortening ◽  
Normal Cells ◽  
Telomere Attrition ◽  
Shelterin Complex ◽  
Alternative Lengthening ◽  
Physiologic Function ◽  
Normal Human

Abstract Telomeres interact with numerous proteins, including components of the shelterin complex, whose alteration, similarly to proliferation-induced telomere shortening, initiates cellular senescence. In tumors, telomere length is maintained by Telomerase activity or by the Alternative Lengthening of Telomeres mechanism, whose hallmark is the telomeric localization of the promyelocytic leukemia (PML) protein. Whether PML contributes to telomeres maintenance in normal cells is unknown. We show that in normal human fibroblasts the PML protein associates with few telomeres, preferentially when they are damaged. Proliferation-induced telomere attrition or their damage due to alteration of the shelterin complex enhances the telomeric localization of PML, which is increased in human T-lymphocytes derived from patients genetically deficient in telomerase. In normal fibroblasts, PML depletion induces telomere damage, nuclear and chromosomal abnormalities, and senescence. Expression of the leukemia protein PML/RARα in hematopoietic progenitors displaces PML from telomeres and induces telomere shortening in the bone marrow of pre-leukemic mice. Our work provides a novel view of the physiologic function of PML, which participates in telomeres surveillance in normal cells. Our data further imply that a diminished PML function may contribute to cell senescence, genomic instability, and tumorigenesis.

scholarly journals Influence of music therapy on the telomere length: a brief review and a pilot study

Biologija ◽  
2019 ◽  
Vol 64 (4) ◽  
Author(s):  
Irina M. Spivak ◽  
Tatiana Yu. Smirnova ◽  
Arina S. Urazova ◽  
Andrey L. Runov ◽  
Anastasia A. Vasilishina ◽  
...  
Keyword(s):  
Music Therapy ◽  
Telomere Length ◽  
Music Perception ◽  
Classical Music ◽  
Telomerase Activity ◽  
Adaptive Performance ◽  
Telomere Shortening ◽  
Age Related ◽  
Psychological Training ◽  
Before And After

Relation between music perception and telomere length is discussed. Telomeres are now considered as markers of general health and as possible predictor of life expectancy, while their length correlates with either the risk of age-related pathologies or with higher adaptive performance. The ability to withstand agerelated telomere shortening by means of practicing psychological training is discussed. Problems and prospects of present-day music therapy are reviewed, as well as absence of studies of alteration of telomere length, related to music perception. Sixty-three practically healthy young (aged 24 ± 5 years) randomly selected Russian-speaking students were divided into three subgroups, each of which listened to music of a specific type for 14 days, 90 minutes each day. Before and after the two-week course, the telomere length and telomerase activity in blood samples were measured. A limited but statistically reliable increase in the telomere length and in telomerase activity is demonstrated to have occurred as a result of completing the music course. Classical music tends to bring about less stress, positively affect one’s mood, and physiology, and, finally, such essential aging markers as telomerase activity and the telomere length. Non-classical music conditioned manifestation of some stress, which tended to affect the telomere length in a negative way. In order to cope with this difficulty, telomerase was activated.

scholarly journals ATR cooperates with CTC1 and STN1 to maintain telomeres and genome integrity in Arabidopsis

2012 ◽  
Vol 23 (8) ◽  
pp. 1558-1568 ◽  
Author(s):  
Kara A. Boltz ◽  
Katherine Leehy ◽  
Xiangyu Song ◽  
Andrew D. Nelson ◽  
Dorothy E. Shippen
Keyword(s):  
Genome Stability ◽  
First Generation ◽  
Telomerase Activity ◽  
Ataxia Telangiectasia Mutated ◽  
Telomere Shortening ◽  
Telomere Attrition ◽  
Damage Response ◽  
Chromosome Fusions ◽  
Repair Genes ◽  
Prolonged Absence

The CTC1/STN1/TEN1 (CST) complex is an essential constituent of plant and vertebrate telomeres. Here we show that CST and ATR (ataxia telangiectasia mutated [ATM] and Rad3-related) act synergistically to maintain telomere length and genome stability in Arabidopsis. Inactivation of ATR, but not ATM, temporarily rescued severe morphological phenotypes associated with ctc1 or stn1. Unexpectedly, telomere shortening accelerated in plants lacking CST and ATR. In first-generation (G1) ctc1 atr mutants, enhanced telomere attrition was modest, but in G2 ctc1 atr, telomeres shortened precipitously, and this loss coincided with a dramatic decrease in telomerase activity in G2 atr mutants. Zeocin treatment also triggered a reduction in telomerase activity, suggesting that the prolonged absence of ATR leads to a hitherto-unrecognized DNA damage response (DDR). Finally, our data indicate that ATR modulates DDR in CST mutants by limiting chromosome fusions and transcription of DNA repair genes and also by promoting programmed cell death in stem cells. We conclude that the absence of CST in Arabidopsis triggers a multifaceted ATR-dependent response to facilitate maintenance of critically shortened telomeres and eliminate cells with severe telomere dysfunction.

scholarly journals Accelerated telomere attrition in children and teenagers with α1-antitrypsin deficiency

2016 ◽  
Vol 48 (2) ◽  
pp. 350-358 ◽  
Author(s):  
Amparo Escribano ◽  
Sara Pastor ◽  
Ana Reula ◽  
Silvia Castillo ◽  
Silvia Vicente ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Risk ◽  
Telomere Length ◽  
Telomerase Activity ◽  
Multiple Hypothesis Testing ◽  
Intermediate Risk ◽  
Telomere Shortening ◽  
Telomere Attrition ◽  
Antitrypsin Deficiency ◽  
Risk Patients

Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of α1-antitrypsin deficiency (AATD), we hypothesised that telomere shortening would be accelerated in AATD patients. This study aimed to assess telomere length in AATD patients and to study its association with α1-antitrypsin phenotypes.Telomere length, telomerase activity, telomerase reverse transcriptase (hTERT) expression and biomarkers of oxidative stress were measured in 62 children and teenagers (aged 2–18 years) diagnosed with AATD and 18 controls (aged 3–16 years).Our results show that intermediate-risk (MZ; SZ) and high-risk (ZZ) AATD patients have significantly shorter telomeres and increased oxidative stress than controls. Correlation studies indicate that telomere length was related to oxidative stress markers in AATD patients. Multiple hypothesis testing revealed an association between telomere length, telomerase activity, hTERT expression and AATD phenotypes; high-risk patients showed shorter telomeres, lower hTERT expression and decreased telomerase activity than intermediate-risk and low-risk patients.AATD patients show evidence of increased oxidative stress leading to telomere attrition. An association between telomere and α1-antitrypsin phenotypes is observed suggesting that telomere length could be a promising biomarker for AATD disease progression.

scholarly journals Gut Microbiota: Critical Controller and Intervention Target in Brain Aging and Cognitive Impairment

2021 ◽  
Vol 13 ◽  
Author(s):  
Hui Li ◽  
Junjun Ni ◽  
Hong Qing
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Healthy Aging ◽  
Brain Aging ◽  
Current Trend ◽  
The Body ◽  
Dietary Interventions ◽  
Age Related ◽  
Functional Features ◽  
The Brain

The current trend for the rapid growth of the global aging population poses substantial challenges for society. The human aging process has been demonstrated to be closely associated with changes in gut microbiota composition, diversity, and functional features. During the first 2 years of life, the gut microbiota undergoes dramatic changes in composition and metabolic functions as it colonizes and develops in the body. Although the gut microbiota is nearly established by the age of three, it continues to mature until adulthood, when it comprises more stable and diverse microbial species. Meanwhile, as the physiological functions of the human body deteriorated with age, which may be a result of immunosenescence and “inflammaging,” the guts of elderly people are generally characterized by an enrichment of pro-inflammatory microbes and a reduced abundance of beneficial species. The gut microbiota affects the development of the brain through a bidirectional communication system, called the brain-gut-microbiota (BGM) axis, and dysregulation of this communication is pivotal in aging-related cognitive impairment. Microbiota-targeted dietary interventions and the intake of probiotics/prebiotics can increase the abundance of beneficial species, boost host immunity, and prevent gut-related diseases. This review summarizes the age-related changes in the human gut microbiota based on recent research developments. Understanding these changes will likely facilitate the design of novel therapeutic strategies to achieve healthy aging.

scholarly journals FOXO3, Telomere Dynamics, and Healthy Brain Aging: A COBRE Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 368-368
Author(s):  
Bradley Willcox ◽  
Kamal Masaki ◽  
Richard Allsopp ◽  
Kalpana Kallianpur
Keyword(s):  
Brain Aging ◽  
Peripheral Blood Leukocyte ◽  
Telomerase Activity ◽  
Cellular Aging ◽  
Human Longevity ◽  
Telomere Shortening ◽  
Wide Range ◽  
Brain Structure And Function ◽  
Blood Leukocyte ◽  
And Function

Abstract Human longevity is linked to genetic, cellular, and other complex biological and psychosocial traits. Aging is typically accompanied by gradual brain atrophy and cognitive decline, but the mechanisms are unclear. Cellular aging, characterized by telomere shortening and altered telomerase activity, is related to mortality and brain aging. Decelerated brain aging is associated with greater peripheral blood leukocyte telomere length (LTL) and, we hypothesize, may be linked to FOXO3 genotype. We will use MRI to assess brain structure and function cross-sectionally in 100 Kuakini Honolulu Heart Program Offspring. Atrophy and disrupted functional connectivity, markers of brain aging, will be examined in relation to FOXO3 and LTL. Associations between brain structural and functional differences, FOXO3 genotype and LTL will be investigated over a wide range of ages, controlling for other biological and psychosocial factors. Results may provide insight into mechanisms influencing the rate of brain aging, and may eventually extend human healthspan.

scholarly journals TECPR2 a positive regulator of autophagy is implicated in healthy brain ageing

2017 ◽  
Author(s):  
John Alexander ◽  
Thomas Ströbel ◽  
Marianthi Georgitsi ◽  
Michael Schuster ◽  
Thomas Penz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Healthy Aging ◽  
Brain Aging ◽  
Neuroprotective Effect ◽  
Cell Cycle Control ◽  
Cell Cycle Checkpoint ◽  
Functional Variants ◽  
Age Related ◽  
Brain Ageing ◽  
Synonymous Variant

ABSTRACTUnderstanding the healthy brain aging process is key to uncovering the mechanisms leading to pathological age-related neurodegeneration, including progression to Alzheimer’s disease (AD). Here, we report the first deep whole genome sequencing study aiming to identify variants that are associated specifically to healthy brain aging defined on both clinical and neuropathological level, thus tacking the issue of pathological heterogeneity that often underlies a clinical AD diagnosis. We studied samples from the VITA brain bank and followed an extreme phenotypic ends study design comparing neuropathologically “healthy” aging individuals above 80 years of age with pure AD patients of the same age. Focusing on the extreme ends of the phenotypic distribution, and potentially functional variants, we discover a single variant (rs10149146) carried by 53.6% of the “healthy” brain elderly individuals in our study (15/28 individuals) and none of the 12 AD cases. This variant lies on the autophagy and cell cycle associated TECPR2 gene. Autophagy dysfunction has been previously implicated in multiple progressive neurodegenerative diseases. An additional non-synonymous variant on the CINP gene (encoding a cell-cycle checkpoint protein) is also found in 46% of healthy controls and absent from all the AD cases. TECPR2 and CINP appear to be “partner” genes in terms of regulation and their associated transcription factors have been previously implicated in AD and neurodegeneration. Our study is the first to support the hypothesis that a TECPR2 non-synonymous variant carries a significant neuroprotective effect pointing to key molecules for the involvement of autophagy and cell cycle control in protection from neurodegeneration.

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