Anti-aging Strategies Research Articles

The influential responsibility of sirtuins in senescence and associated diseases: A review.

Aging is a process of time-associated depletion in the physiological functions, essential for the survival and reproducibility of living beings. Some age-related disorders can be successfully controlled with some biomedical techniques or pharmaceutical approaches. There are some precise remedies that demonstrate conspicuous promise in the preclinical and clinical setup of extending lifespan or enhancing health by altering natural senescence. The sirtuin family of proteins is one of the most favorable targets for antiaging strategies. Sirtuins were initially identified as transcription repressors in yeast, but today they are known to exist in bacteria and eukaryotes, as well as humans. The SIRT (1-7) family of proteins in humans is made up of seven members, each of which has either mono-ADP ribosyl transferase or deacetylase activity. Researchers suggest that sirtuins are essential for cell metabolism and play a major role in how cells react to various stimuli, such as oxidative or genotoxic stress. A healthy lifestyle, which includes exercise and a balanced diet, has been demonstrated to impact health span by adjusting the levels of sirtuins, suggesting the involvement of sirtuins in extending human longevity. The hunt for sirtuin activators is among the most extensive and comprehensive research subjects in the present scenario. Some optimism has been generated to investigate antiaging therapies by natural compounds, such as curcumin and others. This review article highlights the role of sirtuins in native senescence and their primordial roles in the progression of several life-threatening diseases. Further, it also provides recent information on the sirtuin activators and inhibitors and their therapeutic benefits.

Unveiling the causal relationship between circulating levels of micronutrients and risk of facial aging: A Mendelian randomization study.

Facial aging involves a continuous sequence of complex, interrelated events that impact numerous facial tissues. The aim of the study was to elucidate the casual relationship between circulating micronutrients and risk of facial aging. A two-sample Mendelian randomization analysis was performed using genetic data from genome-wide association studies. The inverse-variance weighted method is used for causal effect estimation, and additional tools such as Mendelian randomization-Egger, weighted median, simple mode, and weighted mode were used to refine the analysis. We conducted an in-depth examination of the correlation between several micronutrient blood levels and the risk of facial aging, and identified 3 key micronutrients (selenium, carotene, and iron) that may have a significant impact on skin health. Inverse-variance weighted results indicate that selenium levels were positively correlated with the risk of facial aging (odds ratio [OR] 1.005, P = .027), while a negative causal effect of carotene (OR 0.979, P = .024) and iron (OR 0.976, P = .009) on age-related facial alterations was observed. This study offers a new and insightful perspective on the current understanding of antiaging strategies, particularly the importance of appropriate consumption of essential micronutrients to maintain healthy skin condition.

Effects of light exposure on human ultra-weak photon emission: Preliminary findings for a pioneering control tool in cosmetics

Currently, the cosmetic industry is developing several treatments based on the use of lights with different wavelengths for anti-ageing strategies and facial rejuvenation. Some lights have been proven to be beneficial for our skincare, but their actual effects require an in-depth analysis.Ultra-weak photon emission (UPE) is a spontaneous, low intensity emission from all living systems produced as a consequence of metabolic reactions (e.g., oxidative metabolism, cell division, photosynthesis, or carcinogenesis). However, it can also be induced by several factors, such as light exposure, wounds, thermal shock, and other stress elements. Thus, measuring human biophotonic emission can open new horizons to explore the real benefits of light therapies, particularly regarding the direct relationship between light exposure and free radicals, such as reactive oxygen species (ROS), which are the main cause of UPE.In this study, the ultra-weak photon emission from a sample of ten human beings after exposure to different lights was studied using red and green lights (artificially produced by an RGB LED lamp) and natural light (directly received from the sun), aiming to assess the UPE changes when directly focusing these types of lights on the skin. Hence, this technique could be proposed as a pioneering control tool in cosmetics, principally with phototherapies.Our preliminary results showed that the UPE response after light stimulation differed when a person was exposed to artificial lights compared to sunlight. Besides, there were relevant variations between women and men that should be deeply examined in further investigations by increasing the number of participating subjects in this experience. Furthermore, it was serendipitously discovered that the presence of certain unusual elements in our body, such as using hyaluronic acid fillers and having white hair (natural or dyed), could change the UPE intensity of our skin.

Skin Aging and the Upcoming Role of Ferroptosis in Geroscience.

The skin is considered the most important organ system in mammals, and as the population ages, it is important to consider skin aging and anti-aging therapeutic strategies. Exposure of the skin to various insults induces significant changes throughout our lives, differentiating the skin of a young adult from that of an older adult. These changes are caused by a combination of intrinsic and extrinsic aging. We report the interactions between skin aging and its metabolism, showing that the network is due to several factors. For example, iron is an important nutrient for humans, but its level increases with aging, inducing deleterious effects on cellular functions. Recently, it was discovered that ferroptosis, or iron-dependent cell death, is linked to aging and skin diseases. The pursuit of new molecular targets for ferroptosis has recently attracted attention. Prevention of ferroptosis is an effective therapeutic strategy for the treatment of diseases, especially in old age. However, the pathological and biological mechanisms underlying ferroptosis are still not fully understood, especially in skin diseases such as melanoma and autoimmune diseases. Only a few basic studies on regulated cell death exist, and the challenge is to turn the studies into clinical applications.

Functional hyaluronic acid microneedles for skin photoaging based on collagen induction and oxidative stress regulation strategies

Photoaging holds remarkable importance for skin health and senescence. Ultraviolet (UV) irradiation results in the disruption of the extracellular matrix (ECM) microenvironment, the degradation of collagen, and the generation of oxidative stress. Traditional hyaluronic acid (HA) exhibits a diminished capacity to stimulate collagen regeneration, and hampered by its poor permeability as a macromolecule, ultimately resulting in constrained therapeutic outcomes for the treatment of photoaging. In this study, HA/PX was prepared by functional modification of HA with sulfonate-rich or phosphatidylcholine-rich polymers, which could complement the loss of ECM and ameliorate the senescence of human fibroblasts (HDFs) and hairless mouse models subjected to UVB-induced photoaging. The results indicate that HA/PX exhibits superior abilities in delaying cellular aging, promoting collagen regeneration, and resisting reactive oxygen species (ROS) compared to HA. Furthermore, HA/PX shows good biocompatibility both in vivo and in vitro, without causing allergic reactions or other adverse effects. We also demonstrated that the transdermal delivery of HA/PX via microneedle arrays (MNs) can significantly mitigate wrinkles and skin damage in photoaged nude mice, and achieve the treatment of skin photoaging by enhancing epidermal thickness, promoting collagen deposition, and reducing oxidative stress. Therefore, our research offers a novel possibility for future anti-aging therapeutic strategies.

Mild hyperbaric oxygen exposure protects heart during ischemia/reperfusion and affects vascular relaxation.

Mild hyperbaric oxygen therapy (mHBOT) is an adjuvant therapy used in conditions where tissue oxygenation is reduced and is implemented using pressures less than 1.5 ATA and 100% O2 (instead of the classical HBOT at 1.9-3 ATA) which results in cheaper, easier to implement, and equally effective. mHBOT is offered for wellness and beauty and as an anti-aging strategy, in spite of the absence of studies on the cardiovascular system. Consequently, we investigated the impact of mHBOT on the cardiovascular system. Mechanical and energetic parameters of isolated heart submitted to ischemia/reperfusion injury and arterial contractile response from mHBOT-exposed rats were evaluated. In the heart, mHBOT increased pre-ischemic velocity of contraction and ischemic end-diastolic pressure and developed pressure and contractile economy during reperfusion. mHBOT decreased infarct size and increased the plasma nitrite levels. In the artery, mHBOT increased acetylcholine sensitivity. mHBOT protects the heart during ischemia/reperfusion and affects vascular relaxation.

Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions.

Advancing age is associated with several age-related diseases (ARDs), with musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic conditions contributing towards considerable number of patients, a deeper understanding of bone aging is the need of the hour. One of the underlying factors of bone aging is cellular senescence and its associated senescence associated secretory phenotype (SASP). SASP comprises of pro-inflammatory markers, cytokines and chemokines that arrest cell growth and development. The accumulation of SASP over several years leads to chronic low-grade inflammation with advancing age, also known as inflammaging. The pathways and molecular mechanisms focused on bone senescence and inflammaging are currently limited but are increasingly being explored. Most of the genes, pathways and mechanisms involved in senescence and inflammaging coincide with those associated with cancer and other ARDs like osteoarthritis (OA). Thus, exploring these pathways using techniques like sequencing, identifying these factors and combatting them with the most suitable approach are crucial for healthy aging and the early detection of ARDs. Several approaches can be used to aid regeneration and reduce senescence in the bone. These may be pharmacological, non-pharmacological and lifestyle interventions. With increasing evidence towards the intricate relationship between aging, senescence, inflammation and ARDs, these approaches may also be used as anti-aging strategies for the aging bone marrow (BM).

Changes in human skin composition due to intrinsic aging: a histologic and morphometric study

Skin represents the main barrier against the external environment, but also plays a role in human relations, as one of the prime determinants of beauty, resulting in a high consumer demand for skincare-related pharmaceutical products. Given the importance of skin aging in both medical and social spheres, the present research aims to characterize microscopic changes in human skin composition due to intrinsic aging (as opposed to aging influenced by external factors) via histological analysis of a photoprotected body region. Samples from 25 autopsies were taken from the periumbilical area and classified into four age groups: group 1 (0–12 years), group 2 (13–25 years), group 3 (26–54 years), and group 4 (≥ 55 years). Different traditional histological (hematoxylin–eosin, Masson’s trichrome, orcein, toluidine, Alcian blue, and Feulgen reaction) and immunohistochemical (CK20, CD1a, Ki67, and CD31) stains were performed. A total of 1879 images photographed with a Leica DM3000 optical microscope were morphometrically analyzed using Image ProPlus 7.0 for further statistical analysis with GraphPad 9.0. Our results showed a reduction in epidermis thickness, interdigitation and mitotic indexes, while melanocyte count was raised. Papillary but not reticular dermis showed increased thickness with aging. Specifically, in the papillary layer mast cells and glycosaminoglycans were expanded, whereas the reticular dermis displayed a diminution in glycosaminoglycans and elastic fibers. Moreover, total cellularity and vascularization of both dermises were diminished with aging. This morphometric analysis of photoprotected areas reveals that intrinsic aging significantly influences human skin composition. This study paves the way for further research into the molecular basis underpinning these alterations, and into potential antiaging strategies.

Senolytics and Dietary Phytochemicals: Exploring Anti-Aging Strategies and Mechanisms in Aging and Disease

Senolytics and Dietary Phytochemicals: Exploring Anti-Aging Strategies and Mechanisms in Aging and Disease

Sea cucumber (Acaudina leucoprocta) peptides exhibit anti-aging effect in Drosophila melanogaster via regulation of microbiota dysbiosis and metabolic disorder

As the population ages, the pursuit of extended lifespan and improved healthspan has gained significance. This study assessed the anti-aging properties of sea cucumber peptides derived from Acaudina leucoprocta (SCP) through microbiome and metabolome analyses in Drosophila melanogaster. Supplementation with 0.2%, 0.4%, 0.6%, and 0.8% of SCP significantly boosted the survival rate and extended the mean and median lifespans in both male and female flies. Among them, 0.6% SCP treatment extended the mean and median lifespans of male flies by 21.01% and 25.48 %, which showed the most prominent lifespan-prolonging effect. Moreover, SCP enhanced the healthspan of male flies by improving their climbing ability, intestinal barrier function, and memory performance. Additionally, SCP boosted the survival rate of flies subjected to oxidative, starvation, and heat stress, with no significant effect observed under cold stress conditions. The lifespan-extension effect of SCP remained unaffected by dietary restriction, but was partially inhibited when provided with antibiotic-supplemented food. SCP modulated microbiota with increased the abundance of Lactobacillus, Rhodococcus, and Propioniciclava and decreased Acetobacter, Achromobacter, Pedobacter, and norank_f_Saprospiraceae, which closely related with lifespan-extension effect. Furthermore, SCP induced a metabolic profile in 30-day-old flies more akin to that of 3-day-old flies, impacted 13 significantly regulated metabolites associated with amino acid, nucleotide, and carbohydrate metabolisms. These findings highlight SCP intervention as a promising anti-aging strategy.

SATB1, senescence and senescence-related diseases.

Aging leads to an accumulation of cellular mutations and damage, increasing the risk of senescence, apoptosis, and malignant transformation. Cellular senescence, which is pivotal in aging, acts as both a guard against cellular transformation and as a check against cancer progression. It is marked by stable cell cycle arrest, widespread macromolecular changes, a pro-inflammatory profile, and altered gene expression. However, it remains to be determined whether these differing subsets of senescent cells result from unique intrinsic programs or are influenced by their environmental contexts. Multiple transcription regulators and chromatin modifiers contribute to these alterations. Special AT-rich sequence-binding protein 1 (SATB1) stands out as a crucial regulator in this process, orchestrating gene expression by structuring chromatin into loop domains and anchoring DNA elements. This review provides an overview of cellular senescence and delves into the role of SATB1 in senescence-related diseases. It highlights SATB1's potential in developing antiaging and anticancer strategies, potentially contributing to improved quality of life and addressing aging-related diseases.

Deciphering the Effects of Different Types of Sunlight Radiation on Skin Function: A Review

Sunlight radiation is a fundamental component of our daily lives. Specifically, blue light as well as UV light appear to play a role in the development of oxidative stress, DNA damage, photoaging, and pigmentation through the chromophores in skin tissues. However, several skin problems like psoriasis, eczema, and atopic dermatitis can be avoided with short-duration exposures to low-energy blue light radiation or UV radiation. In addition, exploring the effects of blue light as well as UV radiation on skin is quite essential for the development of minimally invasive antiaging strategies and for the design of innovative cosmetic formulations in modern aesthetics and cosmetology. Thus, in this review, we present the advantages as well as the disadvantages of light radiation, with a special focus on blue light and UV radiation activity on the human skin. We also discuss the molecular action of blue light and UV radiation on human skin. Other types of light radiation are included to holistically approach the effect of light on human skin.

Downregulated SPESP1-driven fibroblast senescence decreases wound healing in aged mice.

Human dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly has not been well defined. This study aims to elucidate the mechanisms of HDFs senescence and how senescent HDFs affect wound healing in aged skin. The expression and function of sperm equatorial segment protein 1 (SPESP1) in skin ageing were evaluated via in vivo and in vitro experiments. To delve into the potential molecular mechanisms by which SPESP1 influences skin ageing, a combination of techniques was employed, including proteomics, RNA sequencing, immunoprecipitation, chromatin immunoprecipitation and liquid chromatography-mass spectrometry analyses. Clearance of senescent cells by dasatinib plus quercetin (D+Q) was investigated to explore the role of SPESP1-induced senescent HDFs in wound healing. Here, we define the critical role of SPESP1 in ameliorating HDFs senescence and retarding the skin ageing process. Mechanistic studies demonstrate that SPESP1 directly binds to methyl-binding protein, leading to Decorin demethylation and subsequently upregulation of its expression. Moreover, SPESP1 knockdown delays wound healing in young mice and SPESP1 overexpression induces wound healing in old mice. Notably, pharmacogenetic clearance of senescent cells by D+Q improved wound healing in SPESP1 knockdown skin. Taken together, these findings reveal the critical role of SPESP1 in skin ageing and wound healing, expecting to facilitate the development of anti-ageing strategies and improve wound healing in the elderly.

A single-cell atlas of lung homeostasis reveals dynamic changes during development and aging

Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung’s development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.

Identification of prospective aging drug targets via Mendelian randomization analysis.

Aging represents a multifaceted process culminating in the deterioration of biological functions. Despite the introduction of numerous anti-aging strategies, their therapeutic outcomes have often been less than optimal. Consequently, discovering new targets to mitigate aging effects is of critical importance. We applied Mendelian randomization (MR) to identify potential pharmacological targets against aging, drawing upon summary statistics from both the Decode and FinnGen cohorts, with further validation in an additional cohort. To address potential reverse causality, bidirectional MR analysis with Steiger filtering was utilized. Additionally, Bayesian co-localization and phenotype scanning were implemented to investigate previous associations between genetic variants and traits. Summary-data-based Mendelian randomization (SMR) analysis was conducted to assess the impact of genetic variants on aging via their effects on protein expression. Additionally, mediation analysis was orchestrated to uncover potential intermediaries in these associations. Finally, we probed the systemic implications of drug-target protein expression across diverse indications by MR-PheWas analysis. Utilizing a Bonferroni-corrected threshold, our MR examination identified 10 protein-aging associations. Within this cohort of proteins, MST1, LCT, GMPR2, PSMB4, ECM1, EFEMP1, and ISLR2 appear to exacerbate aging risks, while MAX, B3GNT8, and USP8 may exert protective influences. None of these proteins displayed reverse causality except EFEMP1. Bayesian co-localization inferred shared variants between aging and proteins such as B3GNT8 (rs11670143), ECM1 (rs61819393), and others listed. Mediator analysis pinpointed 1,5-anhydroglucitol as a partial intermediary in the influence LCT exhibits on telomere length. Circulating proteins play a pivotal role in influencing the aging process, making them promising candidates for therapeutic intervention. The implications of these proteins in aging warrant further investigation in future clinical research.

Anti-aging Strategies and Topical Delivery of Biopolymer-based Nanocarriers for Skin Cancer Treatment.

Environmental factors like UV radiation and epigenetic changes are significant factors for skin cancer that trigger early aging. This review provides essential information on cancer development concerning aging, the receptors involved, and the therapeutic targets. Biopolymers like polysaccharide, polyphenols, proteins, and nucleic acid plays a vital role in the regulation of normal cell homeostasis. Therefore, it is pertinent to explore the role of biopolymers as antiaging formulations and the possibility of these formulations being used against cancer via topical administrations. As UV radiation is one of the predominant factors in causing skin cancer, the association of receptors between aging and cancer indicated that insulin receptor, melatonin receptor, toll-like receptor, SIRT 1 receptor, tumor-specific T cell receptor and mitochondria-based targeting could be used to direct therapeutics for suppression of cancer and prevent aging. Biopolymer-based nanoformulations have tremendously progressed by entrapment of drugs like curcumin and resveratrol which can prevent cancer and aging simultaneously. Certain protein signaling or calcium and ROS signaling pathways are different for cancer and aging. The involvement of mitochondrial DNA mutation along with telomere shortening with a change in cellular energetics leading to genomic instability in the aging process can also induce mitochondrial dysfunction and epigenetic alterations leading to skin cancer. Therefore, the use of biopolymers as a topical supplement during the aging process can result in the prevention of cancer.

Supplementation with Thymbra spicata extract ameliorates lifespan, body-weight gain and Paraquat-induced oxidative stress in Drosophila melanogaster: An age- and sex-related study

Aging represents a decline in function over time. Polyphenols are dietary antioxidants that could exert beneficial effects on aging. This study investigated the effects of dietary supplementation with two extracts from Thymbra spicata L. aerial parts on the lifespan, body-weight control, and antioxidant responses of Drosophila melanogaster cohorts distinguished for age and sex. The aqueous extract extended the lifespan of young female flies, and this pro-longevity potential was associated with a reduction in the body-weight gain. Furthermore, the aqueous extract promoted the antioxidant defense when young females were exposed to Paraquat by reducing oxidative stress and mortality. This study provides the first insight into the beneficial effects of T. spicata supplementation in an animal model, suggesting that the healthy effect could mainly depend on strengthening the antioxidant defenses which reflect on the lifespan. Further investigations will better clarify the mechanisms and potential of T. spicata as nutraceutics in anti-aging strategies.

Newer developments in the treatment of aesthetic lesions caused by excessive exposure of the skin to blue light

Blue light, with wavelengths from 400 nm to 500 nm, is an important part of the sun's electromagnetic radiation spec- trum, which is present in human daily life, especially in the modern era due to the increased use of electronic devices through their screens. Low-energy and low time of expo-sure to blue light can enhance the prevention of certain skin conditions such as psoriasis, eczema, and atopic dermatitis, while studies have demonstrated that prolonged expo- sure to high-energy blue light can increase the amount of skin damage. DNA, cell death, skin barrier and fibroblast damage, hyperpigmentation, and photoaging. Therefore, in the fields of aesthetics and cosmetology, it is important to study the problems caused by exposure to the blue radiation spectrum. Improved protection filters, extracts of plant products, a variety of antioxidants, and natural ingredients from plants and algae are added to cosmetic products and compose innovative formulations as part of a comprehensive photoprotection strategy. In recent decades, antiaging strategies have been developed that include minimally invasive treatments with remarkable safety and efficacy and reduced recovery time. A combined approach of these treatments can provide optimal results in repairing the skin damage caused by ultraviolet (UV) and visible radiation and, consequently, in the overall improvement of the appear- ance of photoaged skin.

Senotherapeutics to Counteract Senescent Cells Are Prominent Topics in the Context of Anti-Ageing Strategies.

Cellular senescence is implicated in ageing and associated with a broad spectrum of age-related diseases. Importantly, a cell can initiate the senescence program irrespective of the organism's age. Various stress signals, including those defined as ageing hallmarks and alterations leading to cancer development, oncogene activation, or loss of cancer-suppressive functions, can trigger cellular senescence. The primary outcome of these alterations is the activation of nuclear factor (NF)-κB, thereby inducing the senescence-associated secretory phenotype (SASP). Proinflammatory cytokines and chemokines, components of this phenotype, contribute to chronic systemic sterile inflammation, commonly referred to as inflamm-ageing. This inflammation is linked to age-related diseases (ARDs), frailty, and increased mortality in older individuals. Additionally, senescent cells (SCs) accumulate in multiple tissues with age and are believed to underlie the organism functional decline, as demonstrated by models. An escalating effort has been dedicated to identify senotherapeutics that selectively target SCs by inducing apoptosis; these drugs are termed senolytics. Concurrently, small molecules that suppress senescent phenotypes without causing cell death are known as senomorphics. Both natural and synthetic senotherapeutics, along with immunotherapies employing immune cell-mediated clearance of SCs, currently represent the most promising strategies to combat ageing and ARDs. Indeed, it is fascinating to observe that information regarding the immune reaction to SCs indicates that regulation by specific lymphocyte subsets, elevated in the oldest centenarians, plays a role in attaining extreme longevity. Regardless, the application of methods already utilized in cancer treatment, such as CAR cells and monoclonal antibodies, broadens the spectrum of potential approaches to be utilized.

Heart-brain mapping: Cardiac atrial function is associated with distinct cerebral regions with high free water in older adults

Left atrial (LA) dysfunction has been linked to cognitive impairment and cerebrovascular dysfunction. Higher brain free-water (FW) derived from diffusion-MRI was associated with early and subtle cerebrovascular dysfunction and more severe cognitive impairment. We hypothesized that LA dysfunction would correlate with higher brain free-water (FW) among healthy older adults. 56 community older adults (73.13 ± 3.56 years; 24 female) with normal cognition and without known cardiovascular disease who had undergone cardiac-MRI, brain-MRI, and neuropsychological assessments were included. Whole-brain voxel-level general linear models were constructed to correlate brain FW measures with LA indices. We found lower scores in LA function measures were related to higher grey matter (GM) FW in regions including orbital frontal and right temporal regions (p < 0.01, family-wise error corrected). In parallel, LA dysfunction was associated with higher FW in white matter (WM) fibres including superior longitudinal fasciculus, internal capsule, and superior corona radiata. However, LA dysfunction was not related to WM tissue reduction and GM cortical thinning. Moreover, these cardiac-related higher brain FW were associated with lower executive function and higher serum B-type natriuretic peptide (p < 0.05, Holm–Bonferroni corrected). These findings may have implications for anti-ageing preventive strategies targeting cardiac and cerebral vascular functions to improve heart and brain outcomes.