The study of longevity and its determinants has been revitalized with the rise of microbiome scholarship. The gut microbiota have been established to play essential protective, metabolic, and physiological roles in human health and disease. The gut dysbiosis has been identified as an important factor contributing to the development of multiple diseases. Accordingly, it is reasonable to hypothesize that the gut microbiota of long-living individuals have healthy antiaging-associated gut microbes, which, by extension, might provide specific molecular targets for antiaging treatments and interventions. In the present study, we compared the gut microbiota of Chinese individuals in two different age groups, long-living adults (aged over 90 years) and elderly adults (aged 65-74 years) who were free of major diseases. We found significantly lower relative abundances of bacteria in the genera Sutterella and Megamonas in the long-living individuals. Furthermore, we established that while biological processes such as autophagy (GO:0006914) and telomere maintenance through semiconservative replication (GO:0032201) were enhanced in the long-living group, response to lipopolysaccharide (GO:0032496), nicotinamide adenine dinucleotide oxidation (GO:0006116), and S-adenosyl methionine metabolism (GO:0046500) were weakened. Moreover, the two groups were found to differ with respect to amino acid metabolism. We suggest that these compositional and functional differences in the gut microbiota may potentially be associated with mechanisms that contribute to determining longevity or aging.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of postmitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a postmitotic cell\'s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. It may be the case that lipofuscin accumulation is the main issue with regard to current age-related disease. Degradation in situ may be an insurmountable task currently. However, a method of systemic lipofuscin removal is discussed herein.

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Chronic stress has been linked to a large number of pathologies, including cancer, premature aging, and neurodegenerative diseases. The accumulation of molecular waste resulting from oxidative and heavy metal-induced stress has been ascribed as a major factor contributing to these diseases. With this in mind, we started by screening 13 small molecules to determine their antistress potential in heavy metal stress-exposed C6 glioblastoma and found that alpha-lipoic acid (ALA) (a natural antioxidant abundantly present in yeast, spinach, broccoli, and meat) was the most effective candidate. We then conducted molecular analyses to validate its mechanism of action. Dose-dependent toxicity assays of cells treated with two ALA enantiomers, R-ALA and S-ALA, showed that they are nontoxic and can be tolerated at relatively high doses. Cells exposed to heavy metal, heat, and oxidative stress showed better recovery when cultured in R-ALA-/S-ALA-supplemented medium, supported by reduction of reactive oxygen species (ROS), aggregated proteins, and mitochondrial and deoxyribonucleic acid (DNA) damage. Molecular analyses revealed protection against stress-induced apoptosis and induction of autophagy in R-ALA- and S-ALA-treated C6/U2OS cells. Consistent with these findings, normal human fibroblasts showed lifespan extension. Taken together, this study demonstrates that lipoic acid has antiaging and antistress potential and warrants further attention in laboratory and clinical studies.

Water is a major requirement for our bodies, and alkaline water has induced an antioxidant response in a model of natural aging. A series of recent reports have shown that aging is related to reduced water intake. Hydrogen-rich water has been suggested to exert a general antioxidant effect in relation to both improving lifestyle and preventing a series of diseases. Here, we wanted to investigate the effect of the daily intake of hydrogen-rich alkaline water (HAW) in counteracting the redox imbalance induced in a model of H2O2-treated mice. Mice were treated with H2O2 for two weeks and either left untreated or supplied with HAW. The results show that HAW induced a reduction in the ROS plasmatic levels that was consistent with the increase in the circulating glutathione. At the same time, the reduction in plasmatic 8-hydroxy-2\'-deoxyguanosine was associated with reduced DNA damage in the whole body. Further analysis of the spleen and bone marrow cells showed a reduced ROS content consistent with a significantly reduced mitochondrial membrane potential and superoxide accumulation and an increase in spontaneous proliferation. This study provides evidence for a clear preventive and curative effect of HAW in a condition of systemic toxic condition and redox imbalance.

The renin-angiotensin system (RAS)-a classical blood pressure regulator-largely contributes to healthy organ development and function. Besides, RAS activation promotes age-related changes and age-associated diseases, which are attenuated/abolished by RAS-blockade in several mammalian species. RAS-blockers also increase rodent lifespan. In previous work, we discussed how RAS-blockade downregulates mTOR and growth hormone/IGF-1 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D-receptor upregulation), and proposed that at least some of RAS-blockade\'s aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS-blockade\'s impact on other aging regulatory pathways, that is, TGF-ß, NF-kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS/RAS-blockade-aging regulatory pathway-mitochondria interactions. However, existing results allow to conjecture that RAS-blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)-even at subclinical doses-offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well-tolerated anti-hypertension therapies in use for over 35 years, investigating their administration to attenuate/prevent aging effects seems simple to implement.

Cosmeceuticals, the bridge between pharmaceuticals and cosmetics, contain biologically active ingredients that may improve the skin\'s overall appearance. As the market, accessibility, and popularity of cosmeceuticals increase, it is essential to understand the safety and efficacy of such products. This systematic review aims to examine published clinical studies involving the use of cosmeceuticals for antiaging to provide evidence-based recommendations based on available efficacy and safety data. PubMed, Embase, and Cochrane were systematically searched on January 1, 2023 using PRISMA guidelines. Strength of evidence was graded using the Oxford Centre for Evidence-Based Medicine guidelines. Clinical recommendations were made based on the quality of the existing literature. A total of 153 articles regarding the use of cosmeceuticals for treatment of antiaging were identified. After screening of titles, abstracts, and full text, 32 studies involving 1236 patients met inclusion criteria, including 20 randomized controlled trials (RCTs) and 12 non-randomized open-label clinical trials for Vitamin C, Retinol, Bakuchiol, Tetrahydrojasmonic acid, Growth Factors, Methyl Estradiolpropanoate, Timosaponin A-III (TA-III), Protocatechuic acid, Grammatophyllum speciosum, and Jasmine rice panicle extract. Retinol and vitamin C for antiaging received a Grade A for recommendation. Methyl estradiolpropanoate, bakuchiol, tetrahydrojasmonic acid, and growth factors received a recommendation grade of C. The remaining ingredients were assigned an inconclusive grade of recommendation due to lack of evidence. Cosmeceuticals included in the review had favorable safety profiles with few significant adverse events. The review analyzes numerous different ingredients to provide an evidence-based approach to decision-making for consumers and physicians on the use of cosmeceuticals for antiaging. Limitations to our review include a limited number of randomized controlled trials and a need for long-term data on each cosmeceutical\'s efficacy and safety. Future research is needed to establish the long-term effectiveness and safety of cosmeceuticals.

UNASSIGNED: Collagen is one of the major proteins of the skin and it is particularly important for its strength and resilience. Skin aging is a natural process that is characterized by the decrease and fragmentation of collagen in the dermis. Oral supplementation with collagen peptides has been clinically shown to have a positive effect on the skin condition. However, the mechanisms of aging-related changes synthesized by cells exposed to collagen are currently not well understood. Therefore, in this in vitro study, the mechanisms associated with collagen, elastin, and versican in human dermal fibroblasts were investigated after exposure to collagen peptides.
UNASSIGNED: The effects of different concentrations of collagen peptides on cell viability and metabolism were analyzed. For gene expression analysis, human dermal fibroblasts were treated with collagen peptides. This was then followed by RNA extraction and DNA synthesis. Gene expressions of collagen type 1 (COL1A1), elastin (ELN), and versican (VCAN) were quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR). In addition, collagen levels were analyzed by confocal scanning laser microscopy using immunostaining.
UNASSIGNED: Collagen peptides tested in the study increased the expression of the relevant COL1A1, ELN, and VCAN genes in human dermal fibroblasts (p < 0.005). Furthermore, confocal microscopy showed increased collagen expression in the dermal fibroblast culture after treatment with the collagen peptides (p < 0.005).
UNASSIGNED: These data provide cell-based evidence for the beneficial effects of exposure to collagen peptides on the skin\'s collagen content and on the molecules that provide firmness and elasticity. This may support the hypothesis that collagen peptides are important for maintaining extracellular matrix (ECM) structure and skin regeneration.

The feces of healthy middle-aged and old people were first transplanted into d-galactose-induced aging mice to construct humanized aging mice with gut microbiota (FMTC) to confirm the antiaging effect of probiotics produced from centenarians. The mouse model was then treated with centenarian-derived Bifidobacterium bifidum (FMTL), Lactobacillus casei (FMTB), and their mixtures (FMTM), and young mice were used as the control. Compared with the FMTC group, the results demonstrated that the probiotics and their combinations alleviated neuronal damage, increased antioxidant capacity, decreased inflammation, and enhanced cognitive and memory functions in aging mice. In the gut microbiota, the relative abundance of Lactobacillus, Ligilactobacillus, and Akkermansia increased and that of Desulfovibrio and Colidextribacter decreased in the FMTM group compared with that in the FMTC group. The three probiotic groups displayed significant changes in 15 metabolites compared with the FMTC group, with 4 metabolites showing increased expression and 11 metabolites showing decreased expression. The groups were graded as Control > FMTM > FMTB > FMTL > FMTC using a newly developed comprehensive quantitative scoring system that thoroughly analyzed the various indicators of this study. The beneficial antiaging effects of probiotics derived from centenarians were quantitatively described using a novel perspective in this study; it is confirmed that both probiotics and their combinations exert antiaging effects, with the probiotic complex group exhibiting a larger effect.

Lactobacillus fermentum can exert antiaging effects, but their roles are strain-specific, and little is known about the molecular mechanisms in some strains. This study investigated the antiaging effects of L. fermentum WC2020 (WC2020) isolated from Chinese fermented pickles and the underlying mechanism of the action in Caenorhabditis elegans. WC2020 enhanced the mean lifespan of L1-stage and L4-stage worms by 22.67% and 12.42%, respectively, compared with Escherichia coli OP50 (OP50), a standard food source for C. elegans. WC2020-induced longevity was accompanied by an increase in body length and mitochondrial transmembrane potential and a reduction in lipid accumulation and the production of reactive oxygen species and malondialdehyde. Moreover, WC2020 increased the production of glutathione, superoxide dismutases, and catalases and altered the transcripts of many phenotype-related genes. Furthermore, WC2020-fed jnk-1 rather than akt-2 or pmk-1 loss-of-function mutants showed similar lifespans to OP50-fed worms. Correspondingly, WC2020 significantly upregulated the expression of jnk-1 rather than genes involved in insulin-like, p38 MAPK, bate-catenin, or TGF-beta pathway. Moreover, the increase in body length, mitochondrial transmembrane potential, and antioxidant capability and the decrease in lipid accumulation induced by WC2020 were not observed in jnk-1 mutants. Additionally, WC2020 increased the expression of daf-16 and the proportion of daf-16::GFP in the nucleus, and increased lifespan disappeared in WC2020-fed daf-16 loss-of-function mutants. In conclusion, WC2020 activated the JNK/DAF-16 pathway to improve mitochondria function, reduce oxidative stress, and then extend the longevity of nematodes, suggesting WC2020 could be a potential probiotic targeting JNK-mediated antioxidant pathway for antiaging in food supplements and bioprocessing. PRACTICAL APPLICATION: Aging has a profound impact on the global economy and human health and could be delayed by specific diets and nutrient resources. This study demonstrated that Lactobacillus fermentum WC2020 could be a potential probiotic strain used in food to promote longevity and health via the JNK-mediated antioxidant pathway.