Is Impaired Proteodynamics a Key to Understand the Biomarkers of Human Cellular Aging?

Background: Life expectancy is increasing all over the world, although neurodegenerative disorders might drastically affect the individual activity of aged people. Of those, Alzheimer’s Disease (AD) is one of the most social-cost age-linked diseases of industrialized countries. To date, retinal diseases seem to be more common in the developing world and characterize principally aged people. Agerelated Macular Degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with AD, including stress stimuli such as oxidative stress, inflammation and amyloid formations. Method: In both diseases, the detrimental intra/extra-cellular deposits have many similarities. Aging, hypercholesterolemia, hypertension, obesity, arteriosclerosis and smoking are risk factors to develop both diseases. Cellular aging routes have similar organelle and signaling patterns in retina and brain. The possibility to find out new research strategies represent a step forward to disclose potential treatment for both of them. Essential trace metals play critical roles in both physiological and pathological condition of retina, optic nerve and brain, by influencing metabolic processes chiefly upon complex multifactorial pathogenesis. Conclusion: Hence, this review addresses current knowledge about some up-to-date investigated essential trace metals associated with AD and AMD. Changes in the levels of systemic and ocular fluid essential metals might reflect the early stages of AMD, possibly disclosing neurodegeneration pathways shared with AD, which might open to potential early detection.

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Production and scavenging of reactive oxygen species both affect reproductive success in male and female Drosophila melanogaster

Biogerontology ◽

10.1007/s10522-021-09922-1 ◽

2021 ◽

Author(s):

Biz R. Turnell ◽

Luisa Kumpitsch ◽

Klaus Reinhardt

Keyword(s):

Reactive Oxygen Species ◽

Drosophila Melanogaster ◽

Reactive Oxygen ◽

Cellular Aging ◽

Ros Production ◽

Oxygen Species ◽

Wild Type ◽

Ros Scavenging ◽

Respiratory Pathway ◽

Male And Female

AbstractSperm aging is accelerated by the buildup of reactive oxygen species (ROS), which cause oxidative damage to various cellular components. Aging can be slowed by limiting the production of mitochondrial ROS and by increasing the production of antioxidants, both of which can be generated in the sperm cell itself or in the surrounding somatic tissues of the male and female reproductive tracts. However, few studies have compared the separate contributions of ROS production and ROS scavenging to sperm aging, or to cellular aging in general. We measured reproductive fitness in two lines of Drosophila melanogaster genetically engineered to (1) produce fewer ROS via expression of alternative oxidase (AOX), an alternative respiratory pathway; or (2) scavenge fewer ROS due to a loss-of-function mutation in the antioxidant gene dj-1β. Wild-type females mated to AOX males had increased fecundity and longer fertility durations, consistent with slower aging in AOX sperm. Contrary to expectations, fitness was not reduced in wild-type females mated to dj-1β males. Fecundity and fertility duration were increased in AOX and decreased in dj-1β females, indicating that female ROS levels may affect aging rates in stored sperm and/or eggs. Finally, we found evidence that accelerated aging in dj-1β sperm may have selected for more frequent mating. Our results help to clarify the relative roles of ROS production and ROS scavenging in the male and female reproductive systems.

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Assessment of the Telomere Length and Its Effect on the Symptomatology of Parkinson’s Disease

Antioxidants ◽

10.3390/antiox10010137 ◽

2021 ◽

Vol 10 (1) ◽

pp. 137

Author(s):

Tina Levstek ◽

Sara Redenšek ◽

Maja Trošt ◽

Vita Dolžan ◽

Katarina Trebušak Podkrajšek

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Telomere Length ◽

Repetitive Sequences ◽

Housekeeping Gene ◽

Cellular Aging ◽

Brain Diseases ◽

Motor Complications ◽

Telomere Attrition ◽

Significant Difference

Telomeres, which are repetitive sequences that cap the end of the chromosomes, shorten with each cell division. Besides cellular aging, there are several other factors that influence telomere length (TL), in particular, oxidative stress and inflammation, which play an important role in the pathogenesis of neurodegenerative brain diseases including Parkinson’s disease (PD). So far, the majority of studies have not demonstrated a significant difference in TL between PD patients and healthy individuals. However, studies investigating the effect of TL on the symptomatology and disease progression of PD are scarce, and thus, warranted. We analyzed TL of peripheral blood cells in a sample of 204 PD patients without concomitant autoimmune diseases and analyzed its association with several PD related phenotypes. Monochrome multiplex quantitative PCR (mmqPCR) was used to determine relative TL given as a ratio of the amount of DNA between the telomere and albumin as the housekeeping gene. We found a significant difference in the relative TL between PD patients with and without dementia, where shorter TL presented higher risk for dementia (p = 0.024). However, the correlation was not significant after adjustment for clinical factors (p = 0.509). We found no correlations between TLs and the dose of dopaminergic therapy when the analysis was adjusted for genetic variability in inflammatory or oxidative factors. In addition, TL influenced time to onset of motor complications after levodopa treatment initiation (p = 0.0134), but the association did not remain significant after adjustment for age at inclusion and disease duration (p = 0.0781). Based on the results of our study we conclude that TL contributes to certain PD-related phenotypes, although it may not have a major role in directing the course of the disease. Nevertheless, this expends currently limited knowledge regarding the association of the telomere attrition and the disease severity or motor complications in Parkinson’s disease.

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Kindness and cellular aging: A pre-registered experiment testing the effects of prosocial behavior on telomere length and well-being

Brain, Behavior, & Immunity - Health ◽

10.1016/j.bbih.2020.100187 ◽

2021 ◽

Vol 11 ◽

pp. 100187

Author(s):

Megan M. Fritz ◽

Lisa C. Walsh ◽

Steven W. Cole ◽

Elissa Epel ◽

Sonja Lyubomirsky

Keyword(s):

Prosocial Behavior ◽

Telomere Length ◽

Well Being ◽

Cellular Aging

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Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes

Scientific Reports ◽

10.1038/s41598-021-84728-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tsung-Po Lai ◽

Mark Simpson ◽

Krunal Patel ◽

Simon Verhulst ◽

Jungsik Noh ◽

...

Keyword(s):

Dna Damage ◽

Preterm Birth ◽

Telomere Length ◽

Human Placenta ◽

Replicative Senescence ◽

Preterm Births ◽

Full Term ◽

Cellular Aging ◽

Telomere Dysfunction ◽

Replicative Aging

AbstractRecent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births.

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Ursodeoxycholic Acid May Inhibit Environmental Aging-Associated Hyperpigmentation

Antioxidants ◽

10.3390/antiox10020267 ◽

2021 ◽

Vol 10 (2) ◽

pp. 267

Author(s):

Ik Jun Moon ◽

Hanju Yoo ◽

Seung Hwan Paik ◽

Hak Tae Kim ◽

Su Yeon Kim ◽

...

Keyword(s):

Ursodeoxycholic Acid ◽

Type I Collagen ◽

Uv Light ◽

Antioxidant Properties ◽

Dermal Fibroblasts ◽

Cellular Aging ◽

Type I ◽

Intracellular Signals ◽

Environmental Aging ◽

Normal Human

Extrinsic aging of the skin caused by ultraviolet (UV) light or particulate matter is often manifested by hyperpigmentation due to increased melanogenesis in senescent skin. Ursodeoxycholic acid (UDCA), which has been commonly used as a health remedy for liver diseases, is known to possess antioxidant properties. This study was done to investigate whether UDCA inhibits cellular aging processes in the cells constituting human skin and it reduces melanin synthesis. ROS, intracellular signals, IL-1α, IL-8, TNF-α, cyclooxygenase (COX)-2, type I collagen, and matrix metalloproteinases (MMPs) levels were measured in human dermal fibroblasts treated with or without UDCA after UV exposure. Melanin levels and mechanistic pathways for melanogenesis were investigated. UDCA decreased ROS, senescence-associated secretory phenotype (SASP), and proinflammatory cytokines induced by UV treatment. UDCA reduced melanogenesis in normal human melanocytes cocultured with skin constituent cells. Our results suggest that UDCA could be a comprehensive agent for the treatment of environmental aging-associated hyperpigmentation disorders.

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Telomere Shortening and Accelerated Aging in US Military Veterans

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041743 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1743

Author(s):

Jeffrey T. Howard ◽

Jud C. Janak ◽

Alexis R. Santos-Lozada ◽

Sarah McEvilla ◽

Stephanie D. Ansley ◽

...

Keyword(s):

Telomere Length ◽

Military Service ◽

Accelerated Aging ◽

Cellular Aging ◽

Veterans Health ◽

Cvd Risk ◽

Base Pairs ◽

Telomere Shortening ◽

Race Ethnicity ◽

Service Data

A growing body of literature on military personnel and veterans’ health suggests that prior military service may be associated with exposures that increase the risk of cardiovascular disease (CVD), which may differ by race/ethnicity. This study examined the hypothesis that differential telomere shortening, a measure of cellular aging, by race/ethnicity may explain prior findings of differential CVD risk in racial/ethnic groups with military service. Data from the first two continuous waves of the National Health and Nutrition Examination Survey (NHANES), administered from 1999–2002 were analyzed. Mean telomere length in base pairs was analyzed with multivariable adjusted linear regression with complex sample design, stratified by sex. The unadjusted mean telomere length was 225.8 base shorter for individuals with prior military service. The mean telomere length for men was 47.2 (95% CI: −92.9, −1.5; p < 0.05) base pairs shorter for men with military service after adjustment for demographic, socioeconomic, and behavioral variables, but did not differ significantly in women with and without prior military service. The interaction between military service and race/ethnicity was not significant for men or women. The results suggest that military service may contribute to accelerated aging as a result of health damaging exposures, such as combat, injury, and environmental contaminants, though other unmeasured confounders could also potentially explain the results.

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Maternal biological age assessed in early pregnancy is associated with gestational age at birth

Scientific Reports ◽

10.1038/s41598-021-94281-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eva E. Lancaster ◽

Dana M. Lapato ◽

Colleen Jackson-Cook ◽

Jerome F. Strauss ◽

Roxann Roberson-Nay ◽

...

Keyword(s):

Risk Factors ◽

Preterm Birth ◽

Early Pregnancy ◽

Gestational Age ◽

Cellular Aging ◽

Biological Age ◽

Potential Candidate ◽

A Genome ◽

Gestational Age At Birth ◽

Age At Birth

AbstractMaternal age is an established predictor of preterm birth independent of other recognized risk factors. The use of chronological age makes the assumption that individuals age at a similar rate. Therefore, it does not capture interindividual differences that may exist due to genetic background and environmental exposures. As a result, there is a need to identify biomarkers that more closely index the rate of cellular aging. One potential candidate is biological age (BA) estimated by the DNA methylome. This study investigated whether maternal BA, estimated in either early and/or late pregnancy, predicts gestational age at birth. BA was estimated from a genome-wide DNA methylation platform using the Horvath algorithm. Linear regression methods assessed the relationship between BA and pregnancy outcomes, including gestational age at birth and prenatal perceived stress, in a primary and replication cohort. Prenatal BA estimates from early pregnancy explained variance in gestational age at birth above and beyond the influence of other recognized preterm birth risk factors. Sensitivity analyses indicated that this signal was driven primarily by self-identified African American participants. This predictive relationship was sensitive to small variations in the BA estimation algorithm. Benefits and limitations of using BA in translational research and clinical applications for preterm birth are considered.

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