Tree-based analysis of longevity predictors and their ten-year changes: a 35-Year mortality follow-up.

BACKGROUND: Prior studies on longevity often examine predictors in isolation and rely solely on baseline information, limiting our understanding of the most important predictors and their dynamic nature. In this study, we used an innovative regression tree model to explore the common characteristics of those who lived longer than their age and sex peers in 35-years follow-up. We identified different pathways leading to a long life, and examined to how changes in characteristics over 10 years (from 1979 to 1989) affect the findings on longevity predictors. METHODS: Data was obtained from the "Tampere Longitudinal Study on Ageing" (TamELSA) in Finland. Survey data was collected in 1979 from 1056 participants aged 60-89 years (49.8% men). In 1989, a second survey was conducted among 432 survivors from the 1979 cohort (40.2% men). Dates of death were provided by the Finnish Population Register until 2015. We employed an individual measure of longevity known as the realized probability of dying (RPD), which was calculated based on each participant's age and sex, utilizing population life tables. RPD is based on a comparison of the survival time of each individual of a specific age and sex with the survival time of his/her peers in the total population. A regression tree analysis was used to examine individual-based longevity with RPD as an outcome. RESULTS: This relative measure of longevity (RPD) provided a complex regression tree where the most important characteristics were self-rated health, years of education, history of smoking, and functional ability. We identified several pathways leading to a long life such as individuals with (1) good self-rated health (SRH), short smoking history, and higher education, (2) good SRH, short smoking history, lower education, and excellent mobility, and (3) poor SRH but able to perform less demanding functions, aged 75 or older, willing to do things, and sleeping difficulties. Changes in the characteristics over time did not change the main results. CONCLUSION: The simultaneous examination of a broad range of potential predictors revealed that longevity can be achieved under very different conditions and is achieved by heterogeneous groups of people.

Elucidating the effective age for dietary restriction and the key metabolites involved.

Dietary restriction (DR) extends lifespan in various species, but its effect at different ages, especially when started later, is unclear. This study used Caenorhabditis elegans to explore the impact of DR at different ages. Worms were divided into control and DR groups, with daily survival monitored. To confirm the occurrence of DR, the expression of DR-sensitive genes namely acdh-1, pyk-1, pck-2 and cts-1 were determined using RT-qPCR. Liquid chromatography mass spectrometry (LC-MS) was employed to observe the changes in metabolites affected by DR. The results indicated that young worms subjected to mild DR displayed the longest lifespan, highlighting the effectiveness of initiating DR at a young age. Increased expression of acdh-1 and pck-2 suggests activation of beta-oxidation and gluconeogenesis, while decreased cts-1 expression indicates a reduced citric acid cycle, further supporting the observed effects of DR in these worms. Metabolomic results indicated that DR decreased the activity of mechanistic Target of Rapamycin (mTOR) and the synthesis of amino acids namely leucine, tyrosine and tryptophan to conserve energy for cell repair and survival. DR also decreased levels of N-acetyl-L-methionine and S-adenosyl-methionine (SAM) in methionine metabolism, thereby promoting autophagy, reducing inflammation, and facilitating the removal of damaged cells and proteins. In conclusion, initiating dietary restriction early in life extends the lifespan by modulating amino acid metabolism and enhancing the autophagy pathway, thereby maintaining cellular wellbeing.

Aging impaired locomotor and biochemical activities in Drosophila melanogaster Oregon R (fruit fly) model.

Despite advancements in healthcare and increased lifespan, aging populations face numerous challenges, including declining cognitive function, increased susceptibility to chronic diseases, and reduced quality of life. This study investigated Aging impaired Locomotors and Biochemical Activities in Drosophila melanogaster Oregon R (Fruit Fly) Model with the aim to elucidate the mechanism involved. Adult wild-type Drosophila melanogaster Oregon R was used for this study. Survival assay, antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA)) and total protein (TP) concentration were investigated. Data obtained were analyzed using R studio and GraphPad Prism. The result indicated low survival in male flies compared to female flies and the highest survival rate was observed with both flies reared together in the same vial. There was impaired locomotor activity in the flies with age. There was a significant decrease in the level of SOD, CAT, GSH and TP with age with a corresponding significant increase in the level of MDA. This finding demonstrated that locomotor activity decreased with aging with decrease performance index and also established the involvement of oxidation through the activities of antioxidant enzymes in aging; decreased (p < 0.05) concentration of antioxidant enzymes and increased (p < 0.05) lipid peroxidation. Also, it demonstrated that female species had longer lifespan compared to males while co-habiting of male and female species extended lifespan.

The Effect of Axenic Dietary Restriction on the Age-Related Changes in Caenorhabditis elegans.

Axenic dietary restriction (ADR) is highly effective in extending lifespan of Caenorhabditis elegans, but its effects on healthspan improvement are less well characterized. Using transmission electron microscopy, morphometric analyses, and functional assays, we found ADR can preserve tissue ultrastructure, including the cuticle, epidermis, and intestinal lumen, and reduce age-associated pathologies like gonad degeneration, uterine tumor clusters, pharyngeal deterioration, and intestinal atrophy. However, there was no notable improvement in behavioral and functional metrics. Our results underscore that lifespan extension through ADR does not inherently translate to broad healthspan improvements.

Life-Course Pathways to Exceptional Longevity: Evidence From the Lothian Birth Cohort of 1921.

BACKGROUND: Longevity, a hallmark of successful aging, is a multifactorial trait with influences from birth onwards. However, limited evidence exists on the pathways linking diverse life-course exposures to longevity, especially within a single cohort. METHODS: We investigated associations between life-course factors and longevity among community-dwelling adults aged 79 (N = 547) from the Lothian Birth Cohort 1921 with a mortality follow-up of 24 years. Cox proportional hazards and structural equation (path) models were used to explore how factors from early life (social class, childhood intelligence quotient [IQ], education), midlife (social class), and later life (health, lifestyle, psychosocial well-being), as well as sex, personality, and apolipoprotein E e4 status, influence survival time in days. RESULTS: During follow-up (1999-2023), 538 participants (98%) died (mean age of death = 89.3 years) and 9 survived (mean age = 101.6 years). Factors associated with lower mortality risk in the multivariable Cox model were higher cognitive function (hazard ratio [HR] = 0.72; 95% confidence interval [CI]: 0.59-0.88), better physical function (HR = 0.61; 95% CI: 0.44-0.85), and greater physical activity (HR = 0.81; 95% CI: 0.71-0.92), while history of cancer was associated with higher mortality risk (HR = 1.84; 95% CI: 1.22-2.77). The life-course path model identified the same direct predictors, with additional contributions from female sex and nonsmoking status, to greater longevity. Early- and midlife factors (IQ, education, social class), and emotional stability, conscientiousness, and female sex, were indirectly and positively associated with survival trajectories via multiple dimensions of adult health. CONCLUSIONS: In understanding why people live to very old ages it is necessary to consider factors from throughout the life course, and to include demographic, psychosocial, and health variables.

Metabolic homeostasis of tissue macrophages across the lifespan.

Macrophages are present in almost all organs. Apart from being immune sentinels, tissue-resident macrophages (TRMs) have organ-specific functions that require a specialized cellular metabolism to maintain homeostasis. In addition, organ-dependent metabolic adaptations of TRMs appear to be fundamentally distinct in homeostasis and in response to a challenge, such as infection or injury. Moreover, TRM function becomes aberrant with advancing age, contributing to inflammaging and organ deterioration, and a metabolic imbalance may underlie TRM immunosenescence. Here, we outline current understanding of the particular metabolic states of TRMs across organs and the relevance for their function. Moreover, we discuss the concomitant aging-related decline in metabolic plasticity and functions of TRMs, highlighting potential novel therapeutic avenues to promote healthy aging.

Healthy Diets and Lifestyles in the World: Mediterranean and Blue Zone People Live Longer. Special Focus on Gut Microbiota and Some Food Components.

Longevity has been associated with healthy lifestyles, including some dietary regimens, such as the Mediterranean diet (MedDiet) and the Blue Zone (BZ) diets. MedDiet relies on a large consumption of fruit, vegetables, cereals, and extra-virgin olive oil, with less red meat and fat intake. Four major BZ have been recognized in the world, namely, Ogliastra in Sardinia (Italy), Ikaria (Greece), the Peninsula of Nicoya (Costa Rica), and Okinawa (Japan). Extreme longevity in these areas has been associated with correct lifestyles and dietary regimens. Fibers, polyphenols, beta-glucans, and unsaturated fatty acids represent the major constituents of both MedDiet and BZ diets, given their anti-inflammatory and antioxidant activities. Particularly, inhibition of the NF-kB pathway, with a reduced release of pro-inflammatory cytokines, and induction of T regulatory cells, with the production of the anti-inflammatory cytokine, interleukin- 10, are the main mechanisms that prevent or attenuate the "inflammaging." Notably, consistent physical activity, intense social interactions, and an optimistic attitude contribute to longevity in BZD areas. Commonalities and differences between MedDIet and BZ diets will be outlined, with special reference to microbiota and food components, which may contribute to longevity.

Evolution of T cells in the cancer-resistant naked mole-rat.

Naked mole-rats (NMRs) are best known for their extreme longevity and cancer resistance, suggesting that their immune system might have evolved to facilitate these phenotypes. Natural killer (NK) and T cells have evolved to detect and destroy cells infected with pathogens and to provide an early response to malignancies. While it is known that NMRs lack NK cells, likely lost during evolution, little is known about their T-cell subsets in terms of the evolution of the genes that regulate their function, their clonotypic diversity, and the thymus where they mature. Here we find, using single-cell transcriptomics, that NMRs have a large circulating population of γδT cells, which in mice and humans mostly reside in peripheral tissues and induce anti-cancer cytotoxicity. Using single-cell-T-cell-receptor sequencing, we find that a cytotoxic γδT-cell subset of NMRs harbors a dominant clonotype, and that their conventional CD8 αßT cells exhibit modest clonotypic diversity. Consistently, perinatal NMR thymuses are considerably smaller than those of mice yet follow similar involution progression. Our findings suggest that NMRs have evolved under a relaxed intracellular pathogenic selective pressure that may have allowed cancer resistance and longevity to become stronger targets of selection to which the immune system has responded by utilizing γδT cells.

Aging as a loss of morphostatic information: A developmental bioelectricity perspective.

Maintaining order at the tissue level is crucial throughout the lifespan, as failure can lead to cancer and an accumulation of molecular and cellular disorders. Perhaps, the most consistent and pervasive result of these failures is aging, which is characterized by the progressive loss of function and decline in the ability to maintain anatomical homeostasis and reproduce. This leads to organ malfunction, diseases, and ultimately death. The traditional understanding of aging is that it is caused by the accumulation of molecular and cellular damage. In this article, we propose a complementary view of aging from the perspective of endogenous bioelectricity which has not yet been integrated into aging research. We propose a view of aging as a morphostasis defect, a loss of biophysical prepattern information, encoding anatomical setpoints used for dynamic tissue and organ homeostasis. We hypothesize that this is specifically driven by abrogation of the endogenous bioelectric signaling that normally harnesses individual cell behaviors toward the creation and upkeep of complex multicellular structures in vivo. Herein, we first describe bioelectricity as the physiological software of life, and then identify and discuss the links between bioelectricity and life extension strategies and age-related diseases. We develop a bridge between aging and regeneration via bioelectric signaling that suggests a research program for healthful longevity via morphoceuticals. Finally, we discuss the broader implications of the homologies between development, aging, cancer and regeneration and how morphoceuticals can be developed for aging.

SuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience.

Graceful healthy ageing and extended longevity is the most desired goal for human race. The process of ageing is inevitable and has a profound impact on the gradual deterioration of our physiology and health since it triggers the onset of many chronic conditions like dementia, osteoporosis, diabetes, arthritis, cancer, and cardiovascular disease. However, some people who lived/live more than 100 years called 'Centenarians" and how do they achieve their extended lifespans are not completely understood. Studying these unknown factors of longevity is important not only to establish a longer human lifespan but also to manage and treat people with shortened lifespans suffering from age-related morbidities. Furthermore, older adults who maintain strong cognitive function are referred to as "SuperAgers" and may be resistant to risk factors linked to cognitive decline. Investigating the mechanisms underlying their cognitive resilience may contribute to the development of therapeutic strategies that support the preservation of cognitive function as people age. The key to a long, physically, and cognitively healthy life has been a mystery to scientists for ages. Developments in the medical sciences helps us to a better understanding of human physiological function and greater access to medical care has led us to an increase in life expectancy. Moreover, inheriting favorable genetic traits and adopting a healthy lifestyle play pivotal roles in promoting longer and healthier lives. Engaging in regular physical activity, maintaining a balanced diet, and avoiding harmful habits such as smoking contribute to overall well-being. The synergy between positive lifestyle choices, access to education, socio-economic factors, environmental determinants and genetic supremacy enhances the potential for a longer and healthier life. Our article aims to examine the factors associated with healthy ageing, particularly focusing on cognitive health in centenarians. We will also be discussing different aspects of ageing including genomic instability, metabolic burden, oxidative stress and inflammation, mitochondrial dysfunction, cellular senescence, immunosenescence, and sarcopenia.

A systematic review of lifespan studies in rodents using stem cell transplantations.

Organismal aging involves the progressive decline in organ function and increased susceptibility to age-associated diseases. Regardless of its origin, cellular aging is consequently reflected at the level of organ and associated systems dysfunction. Aging of stem cell populations within the body and their decreased ability to self-renew, differentiate, and regenerate damaged tissues, is a key contributor to organismal decline. Based on this, supplementing young stem cells may delay tissue aging, improve frailty and extend health and lifespan. This review investigates studies in rodents using stem cell transplantation from either mice or human donors. The aim is to consolidate available information on the efficacy of stem cell therapies in rodent models and provide insights to guide further research efforts. Out of the 21 studies included in this review, the methodology varied significantly including the lifespan measurement. To enable comparison the median lifespan was calculated using WebPlotDigitizer 4.6 if not provided by the literature. A total of 18 out of 21 studies evidenced significant lifespan extension post stem cell transplant, with 7 studies demonstrating benefits in reduced frailty and other aging complications.

Impact of visceral adipose tissue on longevity and metabolic health: a comparative study of gene expression in perirenal and epididymal fat of Ames dwarf mice.

Emerging research underscores the pivotal role of adipose tissue in regulating systemic aging processes, particularly when viewed through the lens of the endocrine hypotheses of aging. This study delves into the unique adipose characteristics in an important animal model of aging - the long-lived Ames dwarf (df/df) mice. Characterized by a Prop1df gene mutation, these mice exhibit a deficiency in growth hormone (GH), prolactin, and TSH, alongside extremely low circulating IGF-1 levels. Intriguingly, while surgical removal of visceral fat (VFR) enhances insulin sensitivity in normal mice, it paradoxically increases insulin resistance in Ames dwarfs. This suggests an altered profile of factors produced in visceral fat in the absence of GH, indicating a unique interplay between adipose tissue function and hormonal influences in these models. Our aim was to analyze the gene expression related to lipid and glucose metabolism, insulin pathways, inflammation, thermoregulation, mitochondrial biogenesis, and epigenetic regulation in the visceral (perirenal and epididymal) adipose tissue of Ames dwarf and normal mice. Our findings reveal an upregulation in the expression of key genes such as Lpl, Adrß3, Rstn, Foxo1, Foxo3a, Irs1, Cfd, Aldh2, Il6, Tnfα, Pgc1α, Ucp2, and Ezh2 in perirenal and Akt1, Foxo3a, PI3k, Ir, Acly, Il6, Ring1a, and Ring 1b in epididymal fat in df/df mice. These results suggest that the longevity phenotype in Ames dwarfs, which is determined by peripubertal GH/IGF-1 levels, may also involve epigenetic reprogramming of adipose tissue influenced by hormonal changes. The increased expression of genes involved in metabolic regulation, tumor suppression, mitochondrial biogenesis, and insulin pathways in Ames dwarf mice highlights potentially beneficial aspects of this model, opening new avenues for understanding the molecular underpinnings of longevity and aging.

Plasma proteomic signature of human longevity.

The identification of protein targets that exhibit anti-aging clinical potential could inform interventions to lengthen the human health span. Most previous proteomics research has been focused on chronological age instead of longevity. We leveraged two large population-based prospective cohorts with long follow-ups to evaluate the proteomic signature of longevity defined by survival to 90 years of age. Plasma proteomics was measured using a SOMAscan assay in 3067 participants from the Cardiovascular Health Study (discovery cohort) and 4690 participants from the Age Gene/Environment Susceptibility-Reykjavik Study (replication cohort). Logistic regression identified 211 significant proteins in the CHS cohort using a Bonferroni-adjusted threshold, of which 168 were available in the replication cohort and 105 were replicated (corrected p value <0.05). The most significant proteins were GDF-15 and N-terminal pro-BNP in both cohorts. A parsimonious protein-based prediction model was built using 33 proteins selected by LASSO with 10-fold cross-validation and validated using 27 available proteins in the validation cohort. This protein model outperformed a basic model using traditional factors (demographics, height, weight, and smoking) by improving the AUC from 0.658 to 0.748 in the discovery cohort and from 0.755 to 0.802 in the validation cohort. We also found that the associations of 169 out of 211 proteins were partially mediated by physical and/or cognitive function. These findings could contribute to the identification of biomarkers and pathways of aging and potential therapeutic targets to delay aging and age-related diseases.

The Recommendation of the Mediterranean-styled Japanese Diet for Healthy Longevity.

The Mediterranean diet, listed as the intangible cultural heritage of humanity by UNESCO, is known as healthy and consumed worldwide. The Japanese diet is also listed and considered healthy. This narrative review compares the Mediterranean diet with its Japanese counterpart. Research has reported that people in Mediterranean regions, such as Italy and Greece, have one-third of the mortality ratio from cardiovascular diseases compared to people in the United States and Northern Europe because of the difference in eating habits. Therefore, Mediterranean diets are considered as healthy. A typical Western diet containing high amounts of fat, sugar, and calories is responsible for several diseases like metabolic syndrome and obesity, which are induced by chronic inflammation. In contrast, Mediterranean and Japanese diets contain them only less. The similarity between Mediterranean and Japanese diets is the substantial intake of vegetables, beans, and fish. On the other hand, the Mediterranean diet consumes large amounts of olive oil, especially polyphenol-rich extra virgin olive oil and dairy products, but meat consumption is relatively small. In contrast, the Japanese diet does not use oil and fat, contains abundant fermented foods, and consumes seaweed. Japan is known for its longevity, and people think that a well-balanced diet daily is good for preventing and curing illness. In this regard, finding non-disease conditions, so-called "ME-BYO," and curing them before the manifestation of diseases is becoming more common. In this review, we discuss the healthy eating habit, "The Mediterranean-styled Japanese diet," which prevents ME-BYO condition and reduces the risk of various diseases. The Mediterranean-styled Japanese diet, a hybrid of Mediterranean and Japanese diets, reduces the risk of various diseases by suppressing chronic inflammation. This nutritional intervention prevents ME-BYO and is beneficial for healthy longevity. Hence, a Mediterranean-styled Japanese diet might be helpful for healthy longevity in Japan and around the world.

Short-term fasting of a single amino acid extends lifespan.

Diet and health are strongly linked, though the strict changes in diet required to improve health outcomes are usually difficult to sustain. We sought to understand whether short-term bouts of amino acid-specific modifications to the diet of Drosophila melanogaster could mimic the lifespan and stress resistance benefits of dietary restriction, without the requirement for drastic reductions in food intake. We found that flies that were transiently fed diets lacking the essential amino acid isoleucine, but otherwise nutritionally complete, exhibited enhanced nicotine tolerance, indicating elevated detoxification capacity. The protection from isoleucine deprivation increased with the duration of exposure, up to a maximum at 7-day isoleucine deprivation for flies 2, 3, or 4 weeks of age, and a 5-day deprivation when flies were 5 weeks of age. Because of these beneficial effects on toxin resistance, we intermittently deprived flies of isoleucine during the first 6 weeks of adulthood and monitored the effect on lifespan. Lifespan was significantly extended when flies experienced short-term isoleucine deprivation at 3 and 5 weeks of age, regardless of whether they were also deprived at 1 week. These results indicate that short-term bouts of isoleucine deprivation can extend lifespan and highlight its cumulative and time-dependent benefits. Interestingly, we found that isoleucine-deprived flies lost their protection against nicotine within 3 days of returning to fully fed conditions. Therefore, the mechanisms underlying lifespan extension may involve transient damage clearance during the bouts of isoleucine deprivation rather than sustained enhanced detoxification capacity. These data highlight a new time-restricted, nutritionally precise method to extend life in Drosophila melanogaster and point to a more manageable dietary method to combat ageing.

Cacao Procyanidins-Induced Lifespan Extension in Caenorhabditis elegans in a Nervous System and CaMKII-Dependent Manner.

Procyanidins are gaining attention due to their potential health benefits. We found that cacao liquor procyanidin (CLPr) from Theobroma cacao seeds increased the lifespan of Caenorhabditis elegans, a representative model organism for aging studies. The genetic dependence of the lifespan-extending effect of CLPr was consistent with that of blueberry procyanidin, which is dependent on unc-43, osr-1, sek-1, and mev-1, but not on daf-16, sir-2.1, or skn-1. The lifespan-extending effect of CLPr was inhibited by neuron-specific RNA interference (RNAi) targeting unc-43 and pmk-1, and in worms with loss-of-function mutations in the odr-3, odr-1, or tax-4 genes, which are essential in sensory neurons, including AWC neurons. It was also inhibited in worms in which AWC neurons or AIB interneurons had been eliminated, and in worms with loss-of-function mutations in eat-4 or glr-1, which are responsible for glutamatergic synaptic transmission. These results suggest that the lifespan-extending effect of CLPr is dependent on the nervous system. In addition, it also requires unc-43 and pmk-1 expression in nonneuronal cells, as demonstrated by the experiments with RNAi in wild-type worms, the neuronal cells of which are not affected by systemic RNAi. The osr-1 gene is expressed in hypodermal and intestinal cells and regulates the response to osmotic stress along with unc-43/calcium/calmodulin-dependent protein kinase II and the p38 mitogen-activated protein kinase pathway. Consistent with this, CLPr improved osmotic stress tolerance in an unc-43- and pmk-1-dependent manner, and it was also dependent on AWC neurons. The lifespan-extending and osmotic-tolerance-improving activities were attributed to procyanidins with a tetrameric or higher-order oligomeric structure.

Intermittent rapamycin feeding recapitulates some effects of continuous treatment while maintaining lifespan extension.

OBJECTIVE: Rapamycin, a powerful geroprotective drug, can have detrimental effects when administered chronically. We determined whether intermittent treatment of mice can reduce negative effects while maintaining benefits of chronic treatment. METHODS: From 6 months of age, male and female C3B6F1 hybrid mice were either continuously fed with 42 mg/kg rapamycin, or intermittently fed by alternating weekly feeding of 42 mg/kg rapamycin food with weekly control feeding. Survival of these mice compared to control animals was measured. Furthermore, longitudinal phenotyping including metabolic (body composition, GTT, ITT, indirect calorimetry) and fitness phenotypes (treadmil, rotarod, electrocardiography and open field) was performed. Organ specific pathology was assessed at 24 months of age. RESULTS: Chronic rapamycin treatment induced glucose intolerance, which was partially ameliorated by intermittent treatment. Chronic and intermittent rapamycin treatments increased lifespan equally in males, while in females chronic treatment resulted in slightly higher survival. The two treatments had equivalent effects on testicular degeneration, heart fibrosis and liver lipidosis. In males, the two treatment regimes led to a similar increase in motor coordination, heart rate and Q-T interval, and reduction in spleen weight, while in females, they equally reduced BAT inflammation and spleen weight and maintained heart rate and Q-T interval. However, other health parameters, including age related pathologies, were better prevented by continuous treatment. CONCLUSIONS: Intermittent rapamycin treatment is effective in prolonging lifespan and reduces some side-effects of chronic treatment, but chronic treatment is more beneficial to healthspan.

Comparing The Mediterranean and The Japanese Dietary Pattern in Relation to Longevity - A Narrative Review.

The Mediterranean dietary pattern (MDP) and Japanese dietary pattern (JDP) have received increasing attention from the scientific community and media, predominantly due to their association with increased longevity and health. Although similarities between the two dietary patterns are evident, a detailed comparison between them is still relatively unexplored. This narrative review aimed to explore the similarities and differences between the MDP and JDP in terms of longevity while also reflecting on the adoption of these diets by other populations outside their regions of origin. Both dietary patterns are plant-based, minimally processed, and sustainable for their respective regions and have been shown to significantly prolong life expectancy in different populations. Nevertheless, these dietary patterns also differ in terms of macronutrient ratios, food preparation and consumption and individual cultural characteristics of each population. Additionally, both dietary patterns are part of broader lifestyle patterns, which include other behaviors, such as abstaining from smoking, engaging in regular physical activity, having low stress levels and a sense of community, spirituality/religiousness and purpose. The promotion of these two dietary patterns should be implemented in other regions after considering cultural and socio-economical characteristics.

The significance of caloric restriction mimetics as anti-aging drugs.

Aging is an intricate process characterized by the gradual deterioration of the physiological integrity of a living organism. This unfortunate phenomenon inevitably leads to a decline in functionality and a heightened susceptibility to the ultimate fate of mortality. Therefore, it is of utmost importance to implement interventions that possess the capability to reverse or preempt age-related pathology. Caloric restriction mimetics (CRMs) refer to a class of molecules that have been observed to elicit advantageous outcomes on both health and longevity in various model organisms and human subjects. Notably, these compounds offer a promising alternative to the arduous task of adhering to a caloric restriction diet and mitigate the progression of the aging process and extend the duration of life in laboratory animals and human population. A plethora of molecular signals have been linked to the practice of caloric restriction, encompassing Insulin-like Growth Factor 1 (IGF1), Mammalian Target of Rapamycin (mTOR), the Adenosine Monophosphate-Activated Protein Kinase (AMPK) pathway, and Sirtuins, with particular emphasis on SIRT1. Therefore, this review will center its focus on several compounds that act as CRMs, highlighting their molecular targets, chemical structures, and mechanisms of action. Moreover, this review serves to underscore the significant relationship between post COVID-19 syndrome, antiaging, and importance of utilizing CRMs. This particular endeavor will serve as a comprehensive guide for medicinal chemists and other esteemed researchers, enabling them to meticulously conceive and cultivate novel molecular entities with the potential to function as efficacious antiaging pharmaceutical agents.