Onset Of Age-related Diseases Research Articles

Early life interventions metformin and trodusquemine metabolically reprogram the developing mouse liver through transcriptomic alterations.

Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering exciting possibilities for enhancing longevity and improving overall health. Metformin (MF), an FDA-approved medication for type II diabetes mellitus, has recently gained attention for its promising anti-aging properties, acting as a calorie restriction mimetic, and delaying precocious puberty. Additionally, trodusquemine (MSI-1436), an investigational drug, has been shown to combat obesity and metabolic disorders by inhibiting the enzyme protein tyrosine phosphatase 1b (Ptp1b), consequently reducing hepatic lipogenesis and counteracting insulin and leptin resistance. In this study, we aimed to further explore the effects of these compounds on young, developing mice to uncover biomolecular signatures that are central to liver metabolic processes. We found that MSI-1436 more potently alters mRNA and miRNA expression in the liver compared with MF, with bioinformatic analysis suggesting that cohorts of differentially expressed miRNAs inhibit the action of phosphoinositide 3-kinase (Pi3k), protein kinase B (Akt), and mammalian target of rapamycin (Mtor) to regulate the downstream processes of de novo lipogenesis, fatty acid oxidation, very-low-density lipoprotein transport, and cholesterol biosynthesis and efflux. In summary, our study demonstrates that administering these compounds during the postnatal window metabolically reprograms the liver through induction of potent epigenetic changes in the transcriptome, potentially forestalling the onset of age-related diseases and enhancing longevity. Future studies are necessary to determine the impacts on lifespan and overall quality of life.

Emerging insights into cuproptosis and copper metabolism: implications for age-related diseases and potential therapeutic strategies.

The expanding geriatric population, whose predisposition toward disabling morbidities and age-related diseases (ARD) is well-documented, has become a paramount social issue, exerting an onerous burden on both the healthcare industry and wider society. ARD manifest as the progressive deterioration of bodily tissues and organs, eventually resulting in the failure of these vital components. At present, no efficacious measures exist to hinder the onset of ARD. Copper, an essential trace element, is involved in a wide range of physiological processes across different cell types. In recent research, a novel variant of copper-dependent cell death, termed cuproptosis, has been identified. This mode of cellular demise stands apart from previously recognized types of cell death. Cuproptosis occurs when copper binds with acyl-CoA synthetase in the tricarboxylic acid (TCA) cycle, resulting in protein aggregation and protein toxicity stress, ultimately leading to cell death. In this paper, we provide a concise overview of the current understanding concerning the metabolism of copper, copper-related diseases, the hallmarks of copper toxicity, and the mechanisms that regulate copper toxicity. Additionally, we discuss the implications of cuproptosis mutations in the development of ARD, as well as the potential for targeting cuproptosis as a treatment for ARD.

Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging.

In the aging process, physiological decline occurs, posing a substantial threat to the physical and mental well-being of the elderly and contributing to the onset of age-related diseases. While traditional perspectives considered the maintenance of life as influenced by a myriad of factors, including environmental, genetic, epigenetic, and lifestyle elements such as exercise and diet, the pivotal role of symbiotic microorganisms had been understated. Presently, it is acknowledged that the intestinal microbiota plays a profound role in overall health by signaling to both the central and peripheral nervous systems, as well as other distant organs. Disruption in this bidirectional communication between bacteria and the host results in dysbiosis, fostering the development of various diseases, including neurological disorders, cardiovascular diseases, and cancer. This review aims to delve into the intricate biological mechanisms underpinning dysbiosis associated with aging and the clinical ramifications of such dysregulation. Furthermore, we aspire to explore bioactive compounds endowed with functional properties capable of modulating and restoring balance in this aging-related dysbiotic process through epigenetics alterations.

Accelerated Aging Induced by an Unhealthy High-Fat Diet: Initial Evidence for the Role of Nrf2 Deficiency and Impaired Stress Resilience in Cellular Senescence.

High-fat diets (HFDs) have pervaded modern dietary habits, characterized by their excessive saturated fat content and low nutritional value. Epidemiological studies have compellingly linked HFD consumption to obesity and the development of type 2 diabetes mellitus. Moreover, the synergistic interplay of HFD, obesity, and diabetes expedites the aging process and prematurely fosters age-related diseases. However, the underlying mechanisms driving these associations remain enigmatic. One of the most conspicuous hallmarks of aging is the accumulation of highly inflammatory senescent cells, with mounting evidence implicating increased cellular senescence in the pathogenesis of age-related diseases. Our hypothesis posits that HFD consumption amplifies senescence burden across multiple organs. To scrutinize this hypothesis, we subjected mice to a 6-month HFD regimen, assessing senescence biomarker expression in the liver, white adipose tissue, and the brain. Aging is intrinsically linked to impaired cellular stress resilience, driven by dysfunction in Nrf2-mediated cytoprotective pathways that safeguard cells against oxidative stress-induced senescence. To ascertain whether Nrf2-mediated pathways shield against senescence induction in response to HFD consumption, we explored senescence burden in a novel model of aging: Nrf2-deficient (Nrf2+/-) mice, emulating the aging phenotype. Our initial findings unveiled significant Nrf2 dysfunction in Nrf2+/- mice, mirroring aging-related alterations. HFD led to substantial obesity, hyperglycemia, and impaired insulin sensitivity in both Nrf2+/- and Nrf2+/+ mice. In control mice, HFD primarily heightened senescence burden in white adipose tissue, evidenced by increased Cdkn2a senescence biomarker expression. In Nrf2+/- mice, HFD elicited a significant surge in senescence burden across the liver, white adipose tissue, and the brain. We postulate that HFD-induced augmentation of senescence burden may be a pivotal contributor to accelerated organismal aging and the premature onset of age-related diseases.

Perspective: Promoting Healthy Aging through Nutrition: A Research Centers Collaborative Network Workshop Report

Within 20 y, the number of adults in the United States over the age of 65 y is expected to more than double and the number over age 85 y is expected to more than triple. The risk for most chronic diseases and disabilities increases with age, so this demographic shift carries significant implications for the individual, health care providers, and population health. Strategies that delay or prevent the onset of age-related diseases are becoming increasingly important. Although considerable progress has been made in understanding the contribution of nutrition to healthy aging, it has become increasingly apparent that much remains to be learned, especially because the aging process is highly variable. Most federal nutrition programs and nutrition research studies define all adults over age 65 y as “older” and do not account for physiological and metabolic changes that occur throughout older adulthood that influence nutritional needs. Moreover, the older adult population is becoming more racially and ethnically diverse, so cultural preferences and other social determinants of health need to be considered. The Research Centers Collaborative Network sponsored a 1.5-d multidisciplinary workshop that included sessions on dietary patterns in health and disease, timing and targeting interventions, and health disparities and the social context of diet and food choice. The agenda and presentations can be found at https://www.rccn-aging.org/nutrition-2023-rccn-workshop. Here we summarize the workshop’s themes and discussions and highlight research gaps that if filled will considerably advance our understanding of the role of nutrition in healthy aging.

Direct neuronal reprogramming of NDUFS4 patient cells identifies the unfolded protein response as a novel general reprogramming hurdle

Mitochondria account for essential cellular pathways, from ATP production to nucleotide metabolism, and their deficits lead to neurological disorders and contribute to the onset of age-related diseases. Direct neuronal reprogramming aims at replacing neurons lost in such conditions, but very little is known about the impact of mitochondrial dysfunction on the direct reprogramming of human cells. Here, we explore the effects of mitochondrial dysfunction on the neuronal reprogramming of induced pluripotent stem cell (iPSC)-derived astrocytes carrying mutations in the NDUFS4 gene, important for Complex I and associated with Leigh syndrome. This led to the identification of the unfolded protein response as a major hurdle in the direct neuronal conversion of not only astrocytes and fibroblasts from patients but also control human astrocytes and fibroblasts. Its transient inhibition potently improves reprogramming by influencing the mitochondria-endoplasmic-reticulum-stress-mediated pathways. Taken together, disease modeling using patient cells unraveled novel general hurdles and ways to overcome these in human astrocyte-to-neuron reprogramming.

DEVELOPING A PROTOCOL TO ASSESS EXPOSURE TO ENVIRONMENTAL POLLUTANTS AMONG OLDER ADULT WOMEN IN SOUTHEAST MICHIGAN

Abstract Environmental pollutants, including PFAS, phthalates, and parabens, contribute to the development of age-related diseases like cancer, cardiometabolic disease, and neurodegenerative diseases. Unfortunately, these chemicals are common in everyday exposures, including drinking water, personal care products (PCPs), non-stick cookware, and food packaging. Exposures to these pollutants may be high in communities that have encountered structural disadvantages; neighborhood disinvestment and decaying infrastructure can make exposures to these pollutants more likely, thus increasing the burden of age-related disease in these communities. Interventions that reduce exposures to these chemicals may prevent or delay the onset of age-related disease, especially in groups experiencing poorer health outcomes because of structural racism and discrimination. To explore the feasibility of a behavior change intervention for older adults that reduces exposure to harmful chemicals in PCPs, a protocol was developed to: 1) Assess attitudes, knowledge, and behaviors related to environmental pollutants via questionnaire; 2) Characterize individual-level ‘exposomes’, the unique mixture of chemicals a person encounters in their everyday lives, by wearing a silicone wristband; 3) Measure environmental exposures in serum. Data collection will begin in September 2023 among older adult women who have participated in the Study of Women’s Health Across the Nation (SWAN) at the Michigan site. Older adults have accrued environmental exposures across their lifetimes, likely in a way that reflects patterns of structural disadvantage. While structural solutions are necessary to address issues of health equity, behavior change efforts can work in tandem to reduce harmful environmental exposures to improve the health of older adults.

A promising therapeutic peptide and preventive/diagnostic biomarker for age-related diseases: The Elabela/Apela/Toddler peptide.

Elabela (ELA), Apela or Toddler peptide is a hormone peptide belonging to the adipokine group and a component of apelinergic system, discovered in 2013-2014. Given its high homology with apelin, the first ligand of APJ receptor, ELA likely mediates similar effects. Increasing evidence shows that ELA has a critical function not only in embryonic development, but also in adulthood, contributing to physiological and pathological conditions, such as the onset of age-related diseases (ARD). However, still little is known about the mechanisms and molecular pathways of ELA, as well as its precise functions in ARD pathophysiology. Here, we report the mechanisms by which ELA/APJ signaling acts in a very complex network of pathways for the maintenance of physiological functions of human tissue and organs, as well as in the onset of some ARD, where it appears to play a central role. Therefore, we describe the possibility to use the ELA/APJ pathway, as novel biomarker (predictive and diagnostic) and target for personalized treatments of ARD. Its potentiality as an optimal peptide candidate for therapeutic ARD treatments is largely described, also detailing potential current limitations.

Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction.

The benefits of regular physical activity are related to delaying and reversing the onset of ageing and age-related disorders, including cardiomyopathy, neurodegenerative diseases, cancer, obesity, diabetes, and fatty liver diseases. However, the molecular mechanisms of the benefits of exercise or physical activity on ageing and age-related disorders remain poorly understood. Mitochondrial dysfunction is implicated in the pathogenesis of ageing and age-related metabolic diseases. Mitochondrial health is an important mediator of cellular function. Therefore, exercise alleviates metabolic diseases in individuals with advancing ageing and age-related diseases by the remarkable promotion of mitochondrial biogenesis and function. Exerkines are identified as signaling moieties released in response to exercise. Exerkines released by exercise have potential roles in improving mitochondrial dysfunction in response to age-related disorders. This review comprehensive summarizes the benefits of exercise in metabolic diseases, linking mitochondrial dysfunction to the onset of age-related diseases. Using relevant examples utilizing this approach, the possibility of designing therapeutic interventions based on these molecular mechanisms is addressed.

Early origins of health and disease risk: The case for investigating adverse exposures and biological aging in utero, across childhood, and into adolescence.

In this article, we suggest that aging and development are two sides of the same coin, and that developing a comprehensive understanding of health and disease risk requires examining age-related processes occurring throughout the earliest years of life. Compared to other periods in life, during this early period of acute vulnerability, when children's biological and regulatory systems are developing, biological aging occurs most rapidly. We review theory and empirical research suggesting that processes of development and aging are intricately linked, and that early adversity may program biological parameters for accelerated aging and disease risk early in life, even though clinical signs of age-related disease onset may not be evident until many years later. Following from this, we make the case for widespread incorporation of biological aging constructs into child development research.

Signs of aging in midlife: physical function and sex differences in microbiota.

Microbiota composition has been linked to physical activity, health measures, and biological age, but a shared profile has yet to be shown. The aim of this study was to examine the associations between microbiota composition and measures of function, such as a composite measure of physical capacity, and biological age in midlife, prior to onset of age-related diseases. Seventy healthy midlife individuals (age 44.58 ± 0.18) were examined cross-sectionally, and their gut-microbiota profile was characterized from stool samples using 16SrRNA gene sequencing. Biological age was measured using the Klemera-Doubal method and a composition of blood and physiological biomarkers. Physical capacity was calculated based on sex-standardized functional tests. We demonstrate that the women had significantly richer microbiota, p = 0.025; however, microbiota diversity was not linked with chronological age, biological age, or physical capacity for either women or men. Men had slightly greater β-diversity; however, β-diversity was positively associated with biological age and with physical capacity for women only (p = 0.01 and p = 0.04; respectively). For women, an increase in abundance of Roseburia faecis and Collinsella aerofaciens, as well as genus Ruminococcus and Dorea, was significantly associated with higher biological age and lower physical capacity; an increase in abundance of Akkermansia muciniphila and genera Bacteroides and Alistipes was associated with younger biological age and increased physical capacity. Differentially abundant taxa were also associated with non-communicable diseases. These findings suggest that microbiota composition is a potential mechanism linking physical capacity and health status; personalized probiotics may serve as a new means to support health-promoting interventions in midlife. Investigating additional factors underlying this link may facilitate the development of a more accurate method to estimate the rate of aging.

Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.

Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older "biological age" compared to their "chronological age". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.

Intimate Partner Violence and Inflammaging: Conflict Tactics Predict Inflammation Among Middle-Aged and Older Adults.

In long-term relationships, conflict is inevitable, but physical and psychological aggression is not. Intimate partner violence (IPV) is a known risk factor for age-related disease onset, and inflammation likely links the two. This study explores relationships between frequency of constructive (i.e., negotiation) and destructive (i.e., aggression) conflict tactics with inflammation in both younger and older adulthood. Based on the theory of inflammaging, the study investigates whether these associations were stronger in mid-to-late adulthood. At one visit, 214 participants in long-term romantic relationships had their blood drawn to assess six inflammatory markers (interleukin-6, IL-6; tumor necrosis factor-alpha, TNF-α; c-reactive protein, CRP; serum amyloid A, SAA; soluble intercellular adhesion molecule, sICAM; soluble vascular cell adhesion molecule, sVCAM) and reported frequency of destructive and constructive conflict tactics with their partner in the past year on the Revised Conflict Tactics Scale short form. Age interacted with number of destructive conflicts per year to predict serum IL-6 (F(1, 200) = 5.3, p = .022), TNF-α (F(1, 180) = 4.2, p = .043), sICAM (F(1, 193) = 7.0, p = .008), and marginally SAA (F(1, 199) = 3.7, p = .055), such that middle-aged and older adults who reported more destructive tactics had higher inflammation. Also, the relationship between constructive conflict frequency and TNF-α also depended on age (F(1, 177) = 4.9, p = .029), in that older adults who reported a greater number of constructive tactics had lower TNF-α. Couples' conflict tactics may influence levels of inflammation, and, therefore, aging rate, in mid-to-late life. Middle-aged and older adults may disproportionately benefit from a healthy partnership and suffer from an unhealthy partnership.

Aging under endocrine hormone regulation.

Aging is a biological process in which the environment interacts with the body to cause a progressive decline in effective physiological function. Aging in the human body can lead to a dysfunction of the vital organ systems, resulting in the onset of age-related diseases, such as neurodegenerative and cardiovascular diseases, which can seriously affect an individual's quality of life. The endocrine system acts on specific targets through hormones and related major functional factors in its pathways, which play biological roles in coordinating cellular interactions, metabolism, growth, and aging. Aging is the result of a combination of many pathological, physiological, and psychological processes, among which the endocrine system can achieve a bidirectional effect on the aging process by regulating the hormone levels in the body. In this paper, we explored the mechanisms of growth hormone, thyroid hormone, and estrogen in the aging process to provide a reference for the exploration of endocrine mechanisms related to aging.

Scientific evidence of foods that improve the lifespan and healthspan of different organisms.

Age is a risk factor for numerous diseases. Although the development of modern medicine has greatly extended the human lifespan, the duration of relatively healthy old age, or 'healthspan', has not increased. Targeting the detrimental processes that can occur before the onset of age-related diseases can greatly improve health and lifespan. Healthspan is significantly affected by what, when and how much one eats. Dietary restriction, including calorie restriction, fasting or fasting-mimicking diets, to extend both lifespan and healthspan has recently attracted much attention. However, direct scientific evidence that consuming specific foods extends the lifespan and healthspan seems lacking. Here, we synthesized the results of recent studies on the lifespan and healthspan extension properties of foods and their phytochemicals in various organisms to confirm how far the scientific research on the effect of food on the lifespan has reached.

Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide and is a significant burden on healthcare systems. α-klotho (klotho) is a protein known for its anti-aging properties and has been shown to delay the onset of age-related diseases. Soluble klotho is produced by cleavage of the full-length transmembrane protein by a disintegrin and metalloproteases, and it exerts various physiological effects by circulating throughout the body. In type 2 diabetes and its complications DN, a significant decrease in klotho expression has been observed. This reduction in klotho levels may indicate the progression of DN and suggest that klotho may be involved in multiple pathological mechanisms that contribute to the onset and development of DN. This article examines the potential of soluble klotho as a therapeutic agent for DN, with a focus on its ability to impact multiple pathways. These pathways include anti-inflammatory and oxidative stress, anti-fibrotic, endothelial protection, prevention of vascular calcification, regulation of metabolism, maintenance of calcium and phosphate homeostasis, and regulation of cell fate through modulation of autophagy, apoptosis, and pyroptosis pathways. Diabetic retinopathy shares similar pathological mechanisms with DN, and targeting klotho may offer new insights into the prevention and treatment of both conditions. Finally, this review assesses the potential of various drugs used in clinical practice to modulate klotho levels through different mechanisms and their potential to improve DN by impacting klotho levels.

Vanillic Acid Improves Stress Resistance and Substantially Extends Life Span in Caenorhabditis elegans.

Aging is the root cause of several pathologies like neurological and cardiovascular diseases. Identifying compounds that improve health span and extend life span, called geroprotectors, could be crucial to preventing or at least delaying the onset of age-related diseases. In this regard, the nematode Caenorhabditis elegans (C.elegans) is emerging as an easy, efficient, low-cost model system to screen natural products and identify novel geroprotectors. Phenolic acids can be found in a wide range of natural products that are part of the human diet. Vanillic acid (VA) is a phenolic acid that has previously been attributed with antioxidant, anti-inflammatory, and neuroprotective features. To determine whether these beneficial health effects amount to an extension of health span and life span, in this work, we thoroughly explore the effect of VA on C.elegans stress resistance and life span. We found that VA increases thermotolerance (19.4%), reduces protein aggregation (between 30% and 40%), improves motility, and extends life span by almost 50%, an extent hardly ever achieved with a natural compound. The increased thermotolerance induced by VA is independent of the insulin/insulin-like growth factor-1 signaling pathway but requires heat shock factor-1 and is associated with increased heat shock protein-4 (HSP-4) and hsp-16.2 expression. These results provide new insight into understanding the therapeutical properties of VA and warrant further investigation of VA as a novel geroprotector.

Blood levels of nicotinic acid negatively correlate with hearing ability in healthy older men

BackgroundAge-related hearing loss (ARHL) is a common phenomenon observed during aging. On the other hand, the decrease in Nicotinamide adenine dinucleotide (NAD +) levels is reported to be closely related to the age-related declines in physiological functions such as ARHL in animal studies. Moreover, preclinical studies confirmed NAD + replenishment effectively prevents the onset of age-related diseases. However, there is a paucity of studies on the relationship between NAD+ metabolism and ARHL in humans.MethodsThis study was analyzed the baseline results of our previous clinical trial, in which nicotinamide mononucleotide or placebo was administered to 42 older men (Igarashi et al., NPJ Aging 8:5, 2022). The correlations between blood levels of NAD+-related metabolites at baseline and pure-tone hearing thresholds at different frequencies (125, 250, 500, 1000, 2000, 4000, and 8000 Hz) in 42 healthy Japanese men aged > 65 years were analyzed using Spearman’s rank correlation. Multiple linear regression analysis was performed with hearing thresholds as the dependent variable and age and NAD+-related metabolite levels as independent variables.ResultsPositive associations were observed between levels of nicotinic acid (NA, a NAD+ precursor in the Preiss-Handler pathway) and right- or left-ear hearing thresholds at frequencies of 1000 Hz (right: r = 0.480, p = 0.001; left: r = 0.422, p = 0.003), 2000 Hz (right: r = 0.507, p < 0.001, left: r = 0.629, p < 0.001), and 4000 Hz (left: r = 0.366, p = 0.029). Age-adjusted multiple linear regression analysis revealed that NA was an independent predictor of elevated hearing thresholds (1000 Hz (right): p = 0.050, regression coefficient (β) = 1610; 1000 Hz (left): p = 0.026, β = 2179; 2000 Hz (right): p = 0.022, β = 2317; 2000 Hz (left): p = 0.002, β = 3257). Weak associations of nicotinic acid riboside (NAR) and nicotinamide (NAM) with hearing ability were observed.ConclusionsWe identified negative correlations between blood concentrations of NA and hearing ability at 1000 and 2000 Hz. NAD+ metabolic pathway might be associated with ARHL onset or progression. Further studies are warranted.Trial registrationThe study was registered at UMIN-CTR (UMIN000036321) on 1st June 2019.Graphical

Potential of Microalgae as Functional Foods Applied to Mitochondria Protection and Healthy Aging Promotion

The rapid aging of the Western countries’ populations makes increasingly necessary the promotion of healthy lifestyles in order to prevent/delay the onset of age-related diseases. The use of functional foods can significantly help to achieve this aim, thanks to the contribution of biologically active compounds suitable to protect cellular and metabolic homeostasis from damage caused by stress factors. Indeed, the excessive production of reactive oxygen species (ROS), favored by incorrect eating and behavioral habits, are considered causal elements of oxidative stress, which in turn favors tissue and organism aging. Microalgae represent a convenient and suitable functional food because of their extraordinary ability to concentrate various active compounds, comprising omega-3 polyunsaturated fatty acids, sterols, phenolic compounds, carotenoids and others. Within cells, mitochondria are the cellular organelles most affected by the accumulation of molecular damage produced by oxidative stress. Since, in addition to producing the chemical energy for cellular metabolism, mitochondria control numerous cell cycle regulation processes, including intrinsic apoptosis, responses to inflammatory signals and other biochemical pathways, their dysfunction is considered decisive for many pathologies. Among these, some degenerative diseases of the nervous system, cardiovascular system, kidney function and even cancer are found. From this viewpoint, bioactive compounds of microalgae, in addition to possessing high antioxidant properties, can enhance mitochondrial functionality by modulating the expression of numerous protective factors and enzymes, which in turn regulate some essential biochemical pathways for the preservation of the functional integrity of the cell. Here, we summarize the current knowledge on the role played by microalgal compounds in the regulation of the mitochondrial life cycle, expression of protective and reparative enzymes, regulation of intrinsic apoptosis and modulation of some key biochemical pathways. Special attention was paid to the composition of some cultivable microalgae strains selected for their high content of active compounds suitable to protect and improve mitochondrial functions.

Lessons from Sicilian centenarians for anti-ageing medicine. The Oxi-inflammatory status

Population ageing is a great achievement of humanity, but it also represents a challenge that the Western world is currently facing, as ageing is associated with increased susceptibility to age-related inflammatory diseases. Therefore, it is necessary to fully understand the mechanisms of healthy ageing to prevent the harmful aspects of ageing. The study of long living ndividuals (LLIs) is a great model for trying to achieve this goal. Accordingly, the oxy-inflammatory status of Sicilian LLIs was reviewed in the present paper. Based on the reported data, anti-inflammatory and anti-oxidative stress strategies have been discussed, useful for delaying or avoiding the onset of age-related diseases, thus favouring a healthy ageing process.