Anti-aging Strategies Research Articles

Pathogenesis and prevention of skin aging

Background: As global life expectancy increases, an interest in maintaining health and beauty in old age has increased. As a barrier organ, the skin is an ideal model for studying both genetically-programmed (intrinsic) and environmentallyinduced (extrinsic) aging.Current Concepts: Among the extrinsic aging factors, solar ultraviolet radiation is the most important, accounting for 80% of facial skin aging. Other nongenetic factors include air pollution, cigarette smoke, nutrition, temperature, sleep, and stress. Through complex interplay, genome, exposome and microbiome all contribute to skin aging. Intrinsic aging causes thinning of the skin and fine wrinkles, while extrinsic aging leads to thick rubbery skin texture, deep wrinkles and dyspigmentation in exposed areas. Fibroblast senescence is a fundamental mechanism of skin aging, with these cells persisting and exhibiting a senescence-associated secretory phenotype which secrets proinflammatory cytokines. Chronic low-level inflammation associated with aging, termed inflamm-aging, is exacerbated by oxidative damage caused by extrinsic factors.Discussion and Conclusion: Understanding the pathogenesis of skin aging may help in developing anti-aging strategies in general. In addition to applying sunscreen every morning and retinoic acid every night, taking antioxidant-rich foods and maintaining a healthy lifestyle are all important for preventing skin aging.

1163-P: Exercise as a Strategy to Decrease Pancreatic ß-Cell Senescence

Age increases the prevalence of type 2 diabetes (T2D) and insulin resistance (IR) accelerates the appearance of senescent β-cells, one of the hallmarks of aging. This suggests that senescence could contribute to the development of T2D and be a novel therapeutic target. In addition to improving blood glucose levels, exercise has been shown to attenuate all hallmarks of aging. However, the effects of exercise upon β-cell senescence remain to be determined. Our hypothesis is that exercise can decrease β-cell senescence and we aim to verify the effects of exercise upon senescence prevention and reversibility under control and IR conditions. Retired breeder male C57Bl/6 mice (6-8 months of age) were randomly assigned into groups (n=5/group): sedentary, exercised (treadmill running, 1 h, 5 times per week, for 2 weeks, at 17 cm/s and 5% incline) and IR (S961, 40nM/week for 2 weeks); exercise was performed at the same time, before or after IR to assess prevention and reversibility. ANOVA Brown-Forsythe and Welch were used to compare groups. Under control conditions, exercise decreased β-cell senescent markers (-58.1% p21Cip1 mRNA and -29% β-Galactosidase activity through FACS sorting), improved glucose tolerance (-13.6% in total area under the curve during intraperitoneal glucose tolerance test) and preserved suppression of basal insulin secretion when compared to sedentary (+39.3% insulin). Exercise performed before and during IR decreased mRNA levels of senescence marker and effector p16Ink4a by 41.7% and 80% respectively. Basal insulin secretion was decreased, and glucose-stimulated insulin secretion restored. When performed after IR, exercise decreased p16Ink4a mRNA by 62.4% and restored basal insulin secretion with no change in the stimulation index. In conclusion, exercise decreased the load of senescent cells in insulin resistant animals. Its effects were more effective before and during IR but it was also able to reverse some of the deleterious effects of IR converting it into a novel β-cell anti-aging strategy. Disclosure P. Carapeto: None. C. Aguayo-mazzucato: Consultant; Self; eGenesis. Funding Joslin Diabetes Center (to C.A-M.); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (to P.C.)

Small Molecule Regulators Targeting NAD+ Biosynthetic Enzymes.

Nicotinamide adenine dinucleotide (NAD+) is a key player in many metabolic pathways as an activated carrier of electrons. In addition to being the cofactor for redox reactions, NAD+ also serves as the substrate for various enzymatic transformations such as adenylation and ADP-ribosylation. Maintaining cellular NAD+ homeostasis has been suggested as an effective anti-aging strategy. Given the importance of NAD+ in regulating a broad spectrum of cellular events, small molecules targeting NAD+ metabolism have been pursued as therapeutic interventions for the treatment of mitochondrial disorders and agerelated diseases. In this article, small molecule regulators of NAD+ biosynthetic enzymes will be reviewed. The focus will be given to the discovery and development of these molecules, the mechanism of action as well as their therapeutic potentials.

Acceleration of ageing via disturbing mTOR-regulated proteostasis by a new ageing-associated gene PC4.

Research on ageing‐associated genes is important for investigating ageing and anti‐ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3‐HDAC complex and inhibits its deacetylated activity, leads to hyper‐acetylation of the histones at the promoters of mTOR‐related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing‐associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing.

Clinical Translation of Anti-aging Associated Genetics: Current Progress and Challenges.

Currently, the focus of anti-aging research has been changed from geriatrics to biogerontology. This has taken anti-aging strategies from cost-effective but palliative therapeutics to active, molecular approaches. Over the years, a large body of basic gerontological research has indicated that the process of biological aging is closely associated with genetic factors. This leads to the development of various gene therapies such as RNA interference technology and results in a subsequent need for translating laboratory achievements into clinical applications. The translation has been a tremendous challenge at this stage with respect to the practicality, safety, and effectiveness of the genetic manipulation techniques. This review summarizes the current development of anti-aging strategies and the progress in the translation of laboratory achievements into clinical applications, highlights challenges encountered, and provides a prospective outlook for future anti-aging research.

Characterization of skin aging through high‐frequency ultrasound imaging as a technique for evaluating the effectiveness of anti‐aging products and procedures: A review

High-frequency ultrasound skin imaging analysis (HFUS) is a non-invasive technique that allows a unique approach to the analysis of skin aging, as well as in evaluating the effectiveness of dermatological and cosmetic products, especially for skin rejuvenation. To describe the impact of skin aging and different anti-aging strategies from the perspective of high-frequency ultrasound. A bibliographic survey was carried out, selecting relevant articles that evaluated the characterization of the skin features from different points of view such as gender (male and female), age (young skin and mature skin), and ethnicity, in addition to individual variations between body regions and daily variations. Some studies also evaluated the impact of cosmetic treatments and esthetic procedures in the skin. Parameters such as dermal thickness, echogenicity, skin texture, and subepidermal low-echogenic band (SLEB) were analyzed. It can be concluded that there is a trend, although not unanimous in the consequences of aging on the skin, being different between men and women, plus the individual nuances resulted from each one's lifestyle and exposure to the sun. As for the technique, it is concluded that high-frequency ultrasound is an important evaluative alternative for dermatological studies and the effectiveness of anti-aging products and treatments.

Plasma from Young Rats Injected into Old Rats Induce Antiaging Effects

An experimental novel antiaging intervention strategy is based on the concept of parabiosis, which involves long-term treatment with factors derived from young blood facilitating rejuvenation of old individuals. In this study, we employed blood plasma from young rats as an intervention strategy to evaluate whether this could impact aging biomarkers in aged rats. The biomarkers studied include: reactive oxygen species, the ferric reducing ability of plasma, plasma membrane redox system, reduced glutathione, malondialdehyde, protein carbonyl, and advanced oxidation protein products in blood. Additionally, the level of tumor necrosis factor-α and interleukin-6 were also estimated in blood. We found that old rats injected with plasma from young rats were protected from oxidative stress. Thus, this study provides some evidence of the rejuvenating effects of young plasma. We hypothesize that young plasma may contain certain "factors," which may be responsible for the observed effects. The mechanism of action is not clearly understood and is open to further studies.

Preserving transcriptional stress responses as an anti‐aging strategy

The progressively increasing frailty, morbidity and mortality of aging organisms coincides with, and may be causally related to, their waning ability to adapt to environmental perturbations. Transcriptional responses to challenges, such as oxidative stress or pathogens, diminish with age. This effect is manifest in the declining function of the stress responsive transcription factor Nrf2. Protective gene expression programs that are controlled by the Drosophila Nrf2 homolog, CncC, support homeostasis and longevity. Age‐associated chromatin changes make these genes inaccessible to CncC binding and render them inert to signal‐dependent transcriptional activation in old animals. In a previous paper, we have reported that overexpression of the CncC dimerization partner Maf‐S counteracts this degenerative effect and preserves organism fitness. Building on this work, we show here that Maf‐S overexpression prevents loss of chromatin accessibility and maintains gene responsiveness. Moreover, the same outcome, along with an extension of lifespan, can be achieved by inducing CncC target gene expression pharmacologically throughout adult life. Thus, pharmacological or dietary interventions that can preserve stress responsive gene expression may be feasible anti‐aging strategies.

Age-Related Pathways in Cardiac Regeneration: A Role for lncRNAs?

Aging imposes a barrier for tissue regeneration. In the heart, aging leads to a severe rearrangement of the cardiac structure and function and to a subsequent increased risk of heart failure. An intricate network of distinct pathways contributes to age-related alterations during healthy heart aging and account for a higher susceptibility of heart disease. Our understanding of the systemic aging process has already led to the design of anti-aging strategies or to the adoption of protective interventions. Nevertheless, our understanding of the molecular determinants operating during cardiac aging or repair remains limited. Here, we will summarize the molecular and physiological alterations that occur during aging of the heart, highlighting the potential role for long non-coding RNAs (lncRNAs) as novel and valuable targets in cardiac regeneration/repair.

Management patterns for skin aging among Saudi dermatologists: A questionnaire-based study.

Background:Skin aging is a complicated process affected by intrinsic, chronological, and extrinsic, environmental, determinants, and it is affected, to a large extent, by exposure to ultraviolet radiation (UVR). The present study aims to assess the antiaging treatment strategies in a real-world setting in Saudi Arabia.Materials and Methods:We conducted an online cross-sectional survey that was conducted from May 2020 to October 2020, involving all eligible dermatologists working at different academic, governmental, and private sectors in Saudi Arabia.Results:A total of 200 dermatologists were included in this study, of them, 33% were aged between 24–35 years. 28.5%, 25.5%, 24.5%, and 21.5% of the participants had 7–10, 4–6, >10, and 0–3 years of practice, respectively. Generally, 80 (40%) of the dermatologists reported that 10–20% of their patients consulting for antiaging, while 50 (25%) reported that 41–60% of their patients consulted for antiaging treatment. Cream products were preferred by 105 (52.5%) of the users. In general, 158 (79%) prescribe growth factors Post-procedures, while 29 (14.5), 24 (12%), and 22 (11%) prescribe them for under-eye dark circles, acne scars, and aging skin, respectively. 124 (62%) prefer to use it in combination with retinoids.Conclusion:The results of this survey indicate the fact that female patients and the age group 31-40 years old are more likely to seek skincare and antiaging therapy. Most dermatologists prescribed growth factors together with retinoids and only a small proportion of them used growth factors are antiaging modalities.

Melatonin to Rescue the Aged Heart: Antiarrhythmic and Antioxidant Benefits.

Aging comes with gradual loss of functions that increase the vulnerability to disease, senescence, and death. The mechanisms underlying these processes are linked to a prolonged imbalance between damage and repair. Damaging mechanisms include oxidative stress, mitochondrial dysfunction, chronodisruption, inflammation, and telomere attrition, as well as genetic and epigenetic alterations. Several endogenous tissue repairing mechanisms also decrease. These alterations associated with aging affect the entire organism. The most devastating manifestations involve the cardiovascular system and may lead to lethal cardiac arrhythmias. Together with structural remodeling, electrophysiological and intercellular communication alterations during aging predispose to arrhythmic events. Despite the knowledge on repairing mechanisms in the cardiovascular system, effective antiaging strategies able to reduce the risk of arrhythmias are still missing. Melatonin is a promising therapeutic candidate due to its pleiotropic actions. This indoleamine regulates chronobiology and endocrine physiology. Of relevance, melatonin is an antiaging, antioxidant, antiapoptotic, antiarrhythmic, immunomodulatory, and antiproliferative molecule. This review focuses on the protective effects of melatonin on age-induced cardiac functional and structural alterations, potentially becoming a new fountain of youth for the heart.

Skin collagen through the lifestages: importance for skin health and beauty

Collagen-based supplements have become a keystone in the management of the ageing process, with proven ability to repair skin damage, bestowing a youthful and healthy appearance sought in the pursuit of beauty. Collagen is an essential scaffold protein that gives smoothness and elasticity to skin, but its production declines with age. Finding ways to tackle this problem is now strongly promoted as an effective way to transform skin and hair, repairing age-related deterioration. A growing number of scientific studies show exciting evidence that it is possible to rejuvenate ageing or damaged skin, improve function of worn joints, and support personal wellbeing and vitality. In recent times, research on the mechanisms which impact the production of collagen in skin and the ideal organization into functional fibres which give skin its characteristic elasticity and firmness has provided new insights into how this bio-scaffold can support cells, tissues and organs. The factors which influence collagen production over a lifetime (e.g., puberty, pregnancy, menopause, andropause), intrinsic factors (e.g., genetics, age, ethnicity) and extrinsic factors (e.g., UV-radiation, pollution, smoking) and the potential for new technologies, ingredients and devices to restore collagen and matrix components to their optimal condition are improving the ability to deliver anti-aging strategies with unprecedented results. This paper will review skin collagen production, structure and function throughout the lifestages, emphasizing its relationship with health, appearance and beauty.

Healthy Aging Biology, Powerful Insight from the Long-Lived Naked Mole-Rat

The naked mole-rat, Heterocephalus glaber, is the longest-lived rodent known with a lifespan in captivity >30 years, 10 times longer than mice, a comparable size rodent. In addition to a particularly long life, it exhibits exceptional resistance to many age-related diseases: cancer, cardiovascular, neurodegenerative, and metabolic diseases. It resists many forms of stress: hypoxia, oxidative stress, and strikingly maintains adequate body composition, fertility, bone quality, and mineral density throughout their long life. The naked mole-rat is a non-traditional animal model that defies the law governing the processes of aging and mortality and provides a powerful tool for the discovery of endogenous molecular anti-aging pathways. Over the past decades, much possible resistance and anti-aging mechanisms have been discovered. These include exclusive physiological mechanisms involved in cellular senescence and its clearance, telomere attrition, genome and proteome stability, stress resistance and metabolism flexibility… This review aims to summarize the many identified anti-aging strategies of the naked mole-rat to better grasp some of the main theories that have been generated. However, many of these theories remain to be fully investigated and confirmed to further understand the complex biology of the naked mole-rat.

From genoprotection to rejuvenation

Aging results from aberrations in signaling mechanisms and decline in biologic activities and cellular functions. Anti-aging strategies include a number of dietary, genetic, and pharmacological interventions that converge on a core network of nutrient sensors including AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), the insulin/insulin-like IIGF) growth factor signaling pathway (IIS), sirtuins, NFkB, and FOXO. Aging can be delayed and life-span and health-span can be extended by calorie and dietary restrictions, administration of NAM, NMN, NR, NAD+, and by antioxidants including hydrogen sulfide. Additional measures for the age related decline in tissue homeostasis include senotherapeutics, senolytics, senomorphics, anti-inflammaging strategies, reactivation of telomerase and prevention of stem cell exhaustion. There is also a possibility to erase the signs of aging and even to reverse aging by epigenetic reprogramming and other emerging measures.

Concept of complications of reproductive aging in women for anti-aging therapy. Literature review

Modern mankind, through the development of medicine and using its scientifically grounded innovations has learned to prolong human life. In Ukraine as in the whole world there is a tendency to increase in life expectancy. Since aging is a natural physiological process, a person from time immemorial has been preoccupied with the search for the so-called “Philosophy Stone” is a substance that prevents aging.This article analyzes data from scientific publications on modern aspects of the problems associated with aging of the female body. It has been proven that aging and anti-aging processes substantiate the individualization of modern approaches to the correction of pre- and perimenopause complications. The general strategy for maintaining of women’s health in peri- and postmenopause according to the International Menopause Society includes menopausal hormone therapy, taking into accounts the therapy goals and individual risk factors. Despite all the desire to give a modern definition of aging, it is currently not possible, therefore in this literature review an attempt is made to analyze the known strategies of premature aging to develop the potential for prolonging active life.In any case, the doctor needs to correlate the benefits and risks of menopausal hormone therapy, taking into account individual risk factors and select appropriate rehabilitation methods aimed at “improving the female face” of the classic image of old age. Since the role of estrogen deficiency in the formation of perimenopausal complications and especially premature aging, is not questioned, anti-aging strategies should be considered a pathogenetically justified method of treating vasomotor, psychosomatic symptoms and sleep disorders, as well as a method of preventing metabolic syndrome. It should be remembered that hormone therapy has a number of limitations and contraindications, which is an incentive for every doctor to contribute to prolongation of the active and healthy life of women 40+ and 50+ years old. Creation of a conceptual model for overcoming the complications of reproductive aging and especially cardiovascular events, osteoporosis, cerebrovascular pathology based on the identification of risk factors will allow to develop the protective anti-aging therapy not only to prolong a woman's life, but also to improve its quality

East to west: research progress in traditional Chinese medicine for antiaging strategies

East to west: research progress in traditional Chinese medicine for antiaging strategies

Effication of amniotic membrane topical stem cell-conditioned medium combined with YAG erbium fractional laser 2940 nm in photoaging skin

Background: Skin ageing is a natural process in humans that is influenced by endogenous and exogenous factors. Nowadays, many people have the concept of health and skin beauty considered as one of the main factors that represent the perception of health in human wellness. Therefore, various anti-ageing therapy strategies that have been developed over the past few years include stem cell therapy. Amniotic Membrane Stem Cells (AMSC) are stem cell products taken from amniotic membranes that contain various proteins and have low immunogenicity. Objective: Proving that Amniotic Membrane Stem Cell (AMSC) metabolite products can improve the clinical picture of photoaging.Method: Study design using one group pre and post-test design model. Samples were obtained by consecutive sampling and the number of samples was 33 people. Clinical examination of patients with the Glogou scale followed by an one smart skin analyzer. Application of AMSC products 3 times daily at intervals of 2 weeks after the Erbium YAG Fractional 2940 nm laser and evaluation were carried out at weeks 0, 4, and 8.Results: Pore diameter showed significant improvement (p<0.001) from first to fifth visit (6.52 ± 0.57 vs 5.79 ± 0.7), wrinkles showed significant improvement (p<0.001) from baseline copared to fifth visit (4.28 ± 0.38 vs 4.09 ± 0.20), pigment, moisture, and skin elasticity showed significant improvement (p<0.001) from the (baseline) compared to fifth consecutive visits (4.35 ± 1.41 vs 3.09 ± 0.68), (42.2 ± 7.64 vs 59.1 ± 7.94), (48.2 ± 14.1 vs 61.7 ± 13.1) respectively. Sebum T Zone and U zone showed significant improvement (p<0.001) from (baseline) and compared to fifth consecutive visit (12325 ± 10616.8 vs 2047.5 ± 1887.9) and (8529.8 ± 9026.8 vs 1560.6 ± 895.7). Side effects of urticaria were found in 1 person.Conclusion: AMSC product therapy can be used as a potential for anti-ageing therapy.

Autophagy in kidney homeostasis and disease.

Autophagy is a conserved lysosomal pathway for the degradation of cytoplasmic components. Basal autophagy in kidney cells is essential for the maintenance of kidney homeostasis, structure and function. Under stress conditions, autophagy is altered as part of the adaptive response of kidney cells, in a process that is tightly regulated by signalling pathways that can modulate the cellular autophagic flux - mammalian target of rapamycin, AMP-activated protein kinase and sirtuins are key regulators of autophagy. Dysregulated autophagy contributes to the pathogenesis of acute kidney injury, to incomplete kidney repair after acute kidney injury and to chronic kidney disease of varied aetiologies, including diabetic kidney disease, focal segmental glomerulosclerosis and polycystic kidney disease. Autophagy also has a role in kidney ageing. However, questions remain about whether autophagy has a protective or a pathological role in kidney fibrosis, and about the precise mechanisms and signalling pathways underlying the autophagy response in different types of kidney cells and across the spectrum of kidney diseases. Further research is needed to gain insights into the regulation of autophagy in the kidneys and to enable the discovery of pathway-specific and kidney-selective therapies for kidney diseases and anti-ageing strategies.

Higher skin autofluorescence detection using AGE-Reader™ technology as a measure of increased tissue accumulation of advanced glycation end products in dialysis patients with diabetes: a meta-analysis.

This meta-analysis was conducted to compare skin autofluorescence (SAF) levels as a measure of advanced glycation end products (AGEs) accumulation between diabetic and non-diabetic dialysis patients. Relevant studies were identified primarily by searching PubMed/MEDLINE and other online databases and manual searching of cross-references. Random-effects model was used to obtain standardized mean differences (SMD) as a summary statistic. Heterogeneity was tested with meta-regression and sub-group analyses. Publication bias and robustness of this meta-analysis were tested using funnel plot and sensitivity analyses. A total of 11 reports comparing SAF between diabetic and non-diabetic dialysis patients were finally included in this meta-analysis. Dialysis patients with diabetes showed significantly higher circulatory SAF levels than their non-diabetic counterparts (SMD = 0.39; P < 0.0001). The difference was more evident in hemodialysis modality (SMD = 0.40; P < 0.0001). A one-study leave-out sensitivity analysis validated the robustness of this meta-analysis. The presence of diabetes in dialysis patients is associated with increased AGEs accumulation reflected through SAF measurements using a novel and non-invasive AGE-Reader™ technology. Our findings are in support of considering anti-AGE therapeutic strategies in addition to standard glycemic management in dialysis patients with diabetes.

Thermal-induced hydrosilylation to endow nanoporous silicon energetic films with long-term chemical stability

The huge energy release and highly adjustable combustion characteristics of nanoporous silicon (nPS) make it one of the most attractive inorganic energetic materials. However, nPS will be oxidized slowly from its surface when it is left in ambient air to be aged. Explanations vary as to the aging mechanism, and the corresponding anti-ageing strategy remains to be fully investigated. The present study provides an efficient strategy of a thermal-induced hydrosilylation to improve the long-term chemical stability of H-terminated nPS. The nPS of 75 μm in depth was etched with a pore diameter of 52.5 nm and a gravimetry-determined porosity of 79.6%. The DSC and FTIR data confirm that oxygen is able to infiltrate the H-terminated layer and preferentially attack the weak Si-Si over Si-H bonds. The prime oxidizer is not sodium perchlorate but oxygen from the air to cause a backbond oxidation. After a modification, the heat of reaction is determined to be 1436 J·g−1. Interestingly, this value is of almost no detectable change to be 1402 J·g−1 and 1387 J·g−1 when aged for 24 or 48 h, respectively. All the evidences suggest that the alkyl-terminated nPS exhibits an excellent anti-oxidation ability to ambient air, which is well consistent with a high-speed video analysis from the combustion behavior of nPS impregnated with NaClO4·H2O. This work suggests that only one step may be away from a practical application of nPS energetic materials.