Aging is closely associated with mitochondrial dysfunction, oxidative stress, and impaired activation of the Nrf2 signaling pathway and all of these contribute to cellular senescence and subsequent cell death. Mitochondrial dysfunction in oxidative stress as well as Mitohormesis on the other hand, remains a paradoxical phenomenon in stress induced ageing and the role of cellular antioxidant like ubiquinol (CoQ10) remains least explored highlighting the need for more research. The present study investigated the cytoprotective properties of ubiquinol in UV-exposed L929 fibroblast cells, emphasizing its dual role in mitigating oxidative damage and enhancing mitochondrial function. Viability results depicted that lower concentrations of ubiquinol (6.25 and 12.5 μg/mL) effectively improved cell viability, reduced ROS levels, and significantly mitigated UV-induced DNA damage, as evidenced by comet assay results. Importantly, ubiquinol treatment enhanced Nrf2 translocation to the nucleus, activating the cell's endogenous antioxidant defense system and promoting cellular resilience attributing to cellular homeostasis. Additionally, ubiquinol mitigated mitochondrial membrane potential (MMP), preventing UV-induced mitochondrial depolarization, a hallmark of dysfunction. This protective effect against mitochondrial damage underscores ubiquinol’s role in maintaining mitochondrial homeostasis in stress induced condition. Moreover, a reduction in senescence-associated β-galactosidase staining was observed, indicating that ubiquinol effectively counteracted cellular senescence. These findings highlight the complex interplay between oxidative stress, mitochondrial function, and Nrf2 activation in aging and Ubiquinol’s ability to mitigate oxidative stress while simultaneously supporting mitochondrial bioenergetics and Nrf2-driven antioxidant responses positions it as a promising cytoprotective compound against UV-induced stress. The experimental results proposes that oxidative homeostasis is revisited in exogenous supplementation of ubiquinol at lower concentrations suggesting that while mild mitochondrial stress may promote longevity, ubiquinol's mitigation of mitochondrial function and oxidative balance could offer a complementary route to achieve cellular wellbeing.
Mitochondrial dysfunction is a hallmark of aging, affecting multiple systems and tissues, contributing to impairments in function. The resultant decreases in energy availability, along with increased oxidative stress, may be attenuated through diet. Fasting paradigms (including time restricted feeding (TRF)) and ketogenic diets (keto) both influence mitochondrial function, potentially mitigating these effects. However, the duration and modality of dietary intervention required for ameliorating age-related mitochondrial impairments remain unknown. Therefore, this study investigated the effects of a chronically (8-24 months; cTRFc) and acutely (22-24 months; aTRFc) administered TRF diet with standard macronutrients, as well as a chronically (8-24 months) administered TRF with ketogenic macronutrients (cTRFk), on mitochondrial activity and gene expression in aged male rats across tissues (brain, liver, muscle). Despite some synergy across the chronic diet groups, keto and TRF duration influenced mitochondrial function in a tissue- and diet-specific manner. Mitochondrial complex II activity was higher in cTRFk rats within the liver. Mitochondrial complex IV activity was lower in muscle and hippocampal tissue in both chronic TRF-fed groups. Relatedly, expression of the complex IV-related gene Cox2 increased within the CA3 subregion of the hippocampus of cTRFk. In this same region, expression of the mitochondrial biogenesis related gene Pgc1a was increased in cTRFc diet rats only. Within the liver, Cox5b expression increased in both groups of chronic TRF rats. Together, these findings highlight complex, tissue-specific responses to long-term dietary interventions, emphasizing the need for further research to develop targeted nutritional strategies for enhancing mitochondrial function and metabolic health in aging populations.
Diabetes management has evolved beyond glycemic control, with emerging evidence demonstrating the multi-system benefits of various anti-diabetic drug classes. This review examines the mechanisms, pharmacokinetics, and therapeutic potential of Glucagon-like Peptide-1 (GLP-1) receptor agonists, Dipeptidyl Peptidase-4 (DPP-4) inhibitors, Sodium- Glucose Cotransporter-2 (SGLT-2) inhibitors, and Thiazolidinediones (TZDs). These agents not only regulate blood glucose but also confer cardiovascular, neuroprotective, renal, and anti-aging effects, positioning them as promising candidates for broader metabolic disorder management. GLP-1 receptor agonists enhance insulin secretion, support weight loss, and exhibit neuroprotective and cardiovascular benefits. DPP-4 inhibitors, which increase endogenous GLP-1 levels, offer stroke prevention and cognitive advantages, particularly in patients with renal impairment. SGLT-2 inhibitors lower blood sugar independently of insulin, reduce heart failure risk, slow kidney disease progression, and possess senolytic properties that may enhance longevity. While TZDs improve insulin sensitivity and beta-cell function, their cardiovascular risks necessitate cautious use. Beyond diabetes, these drugs modulate inflammation, oxidative stress, and metabolic dysfunction—key factors in aging and chronic disease progression. The senolytic potential of SGLT-2 inhibitors, the neurotrophic effects of GLP-1 receptor agonists, and the cardiovascular benefits of DPP-4 inhibitors highlight their broader therapeutic applications. This review underscores a paradigm shift in diabetes management toward a personalized medicine approach. As research advances, integrating these agents into anti-aging and chronic disease prevention strategies may redefine future medical treatments, emphasizing healthier aging and extended lifespan.
Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease and results from cerebrovascular pathology leading to brain tissue damage. This mini-review synthesizes current evidence on the interplay between diet, gut microbiota, and inflammation in the pathogenesis of VaD. Despite its significant global prevalence, there remains no effective pharmacological treatment for VaD, highlighting the need for preventative strategies. Emerging research suggests that the gut microbiome, diet, and systemic inflammation may collectively play a crucial role in the development and progression of VaD. The gut microbiome, a key regulator of immune function, has been implicated in neuroinflammation and cognitive decline, with microbial imbalances associated with elevated systemic inflammation and breakdown of blood brain barrier integrity. Furthermore, dietary patterns influence both gut microbiota composition and inflammatory status, with pro-inflammatory diets correlating with higher dementia risk and anti-inflammatory diets showing potential neuroprotective effects. A better understanding of these relationships could inform novel prevention and treatment strategies, including microbiome-targeted therapies such as probiotics and faecal microbiota transplantation.
Background Aging induces structural remodeling, altering atrial electrogram morphology. Over time, structural and consequently electrical remodeling creates a substrate for atrial fibrillation. In structural heart disease, age-induced remodeling comes on top of a pre-existing degree of structural remodeling due to pressure or volume overload. Objective Investigate the severity of age-related electrical remodeling in patients undergoing surgery for structural heart disease by utilizing a high resolution epicardial mapping approach. Methods Five seconds of sinus rhythm were recorded intraoperatively at the right atrium (RA), Bachmann's bundle (BB), the left atrium, and the pulmonary vein area. Potential voltage, low-voltage area (LVA) and conduction velocity (CV) were assessed in all regions. Results 104 patients were included (62,5 % male, age: 26–84 years) and categorized in three age groups: young-age (age <60 years, n = 40), middle-age (age 60–71 years, n = 33), or old-age (age ≥72 years, n = 31) group. Compared to the young-age group, the old-age group had 1) lower median potential voltages at RA (4.65 [3.53–5.62]mV versus 5.94 [4.86–6.79]mV, p = 0.001) and 2) lower CV at RA (87.86 [82.53–96.67]cm/s versus 94.81 [90.14–98.59]cm/s, p = 0.016) and BB (83.38 [67.72–94.96]cm/s versus 98.84 [86.58–102.90]cm/s, p = 0.005). Conclusions Age-related electrophysiological changes in patients with structural heart disease include reduction in atrial potential voltages and slowing of CV. These changes were less pronounced in the middle-age group. This indicates that electrical remodeling is a combination of both the underlying heart disease and the aging process. However, the less pronounced changes in the middle-age group may reflect a more gradual progression of age-related remodeling.
Although small vessel vascular dementia (SmVD) remains a significant contributor to global disease burden, its aetiology and pathogenesis are not fully understood. Past research has highlighted an association of SmVD with blood-brain barrier (BBB) dysfunction and neuroinflammation. Studies of claudin-1 polymorphisms and serum cytokines have been found to be useful biomarkers and offer possible mechanistic relationship. However, the pathophysiology and primary factors that contribute to the development and onset of SmVD remain to be further elucidated. This study aimed to evaluate the association of these biomarkers with SmVD through the construction of a logistic regression model. Two datasets from a study group, sourced from the publications of “Association of genetic polymorphisms of claudin-1 with small vessel VD” and “Macrophage and microglia related chemokines are associated with small vessel (white matter) VD: A case-control study”, were merged with multiple imputation chain equations to allow for the construction of a unified logistic regression model. The model incorporated an L2 regularisation penalty to improve the interpretability of the findings. The results showed a significant link between disease comorbidities and SmVD, particularly those with a history of stroke and Parkinson's diseases, while cytokines displayed a weaker association with SmVD. Overall, this study supported the mechanistic theories linking SmVD with BBB dysfunction and neuroinflammation.
Background: Aging is the strongest risk factor for neurodegenerative diseases and has been implicated in important changes in the brain. Rodents, such as mice, have been used to understand age-related changes in brain function, and aging has been studied using senescence-accelerated mouse (SAM) strains. Accumulating evidence indicates that SAM-prone (SAMP)8 and SAMP10 strains have learning disabilities. However, in previous studies, these strains were not subjected to a series of behavioural tests. In behavioural experiments, it is necessary to conduct a behavioural test battery to consider various aspects, including sources of variability and experimental interference. Method: This study aimed to comprehensively characterize behavioural abnormalities in SAMP8 and SAMP10 mice using a standardized battery of behavioural tests. We conducted a series of behavioural tests (neuromuscular strength, elevated plus maze, light-dark transition, open field, Y-maze, and passive avoidance tests) to investigate behaviour in SAMP8 and SAMP10 strains. We used 12-month-old male mice in this study. Results: SAMP8 and SAMP10 mice exhibited abnormal behaviour in the present behavioural tests. Body weight, body temperature, muscle strength, and motor learning differed between SAMP8 or SAMP10 and SAMR1 mice. These differences may underlie variations in anxiety-like behaviours and locomotor activity. Conclusion: Together, these findings highlight the utility of SAMP8 and SAMP10 mice as models for studying age-related functional decline in the brain.
Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by the gradual loss of dopaminergic neurons in the substantia nigra, resulting in both motor and non-motor symptoms. A defining feature of PD pathology is the presence of Lewy bodies, which are intracellular inclusions primarily composed of aggregated alpha-synuclein (α-syn) proteins. The abnormal buildup of α-syn, referred to as α-synucleopathy, is a key aspect of PD and other neurodegenerative conditions. Recent research indicates that bacterial amyloids, such as curli proteins produced by Escherichia coli, may influence α-syn aggregation, potentially playing a role in PD development. These discoveries provide a new perspective on the involvement of microbial factors in neurodegenerative diseases, suggesting that curli proteins can cross-seed with α-syn and enhance its aggregation. Understanding these interactions opens up new therapeutic possibilities, including methods to inhibit curli production, prevent curli-α-syn interactions, or target the resulting pathological aggregates. Such therapeutic strategies could offer promising new ways to slow or stop the progression of PD and improve outcomes for patients.
LINE-1 (L1) and Alu are two families of transposable elements (TEs) occupying ~17% and ~11% of the human genome, respectively. Though only a small fraction of L1 copies is able to produce the machinery to mobilize autonomously, Alu and degenerate L1s can hijack their functional machinery and mobilize in trans. The expression and subsequent mobilization of L1 and Alu can exert pathological effects on their hosts. These features have made them promising focus subjects in studies of aging where they can become active. However, mechanisms regulating TE activity are incompletely characterized, especially in diverse human populations. To address these gaps, we leveraged genomic data from the 1000 Genomes Project to carry out a trans-ethnic GWAS of L1/Alu insertion singletons. These are rare, recently acquired insertions observed in only one person and which we used as proxies for variation in L1/Alu insertion numbers. Our approach identified SNVs in genomic regions containing genes with potential and known TE regulatory properties, and it enriched for SNVs in regions containing known regulators of L1 expression. Moreover, we identified reference TE copies and structural variants that associated with L1/Alu singletons, suggesting their potential contribution to TE insertion number variation. Finally, a transcriptional analysis of lymphoblastoid cells highlighted potential cell cycle alterations in a subset of samples harboring L1/Alu singletons. Collectively, our results suggest that known TE regulatory mechanisms may be active in diverse human populations, expand the list of loci implicated in TE insertion number variability, and reinforce links between TEs and disease.
Background The hypothesis that metabolic rate (MR) is inversely correlated with lifespan has long been debating. Another area of controversy is the relationship between MR and time-flow perception (TFP), and aging. Objectives: to study the impact of overweight and excess food intake on MR, TFP, chronic diseases, aging, lifespan. Methods Design: a systematic review. Settings: Web of Science, Scopus, Science Direct, Kopernio, PubMed, and Mendeley were searched for articles published for 44 years (1979-2022). The study bases on a systematic literature review of 3612 articles published worldwide. Results In total, 107 full-text articles were assessed for eligibility. Overweight/overeating accelerates MR, leading to a hyper-metabolic mode of the body. MR and lifespan are inversely correlated. TFP depends on MR; accelerated MR provides TFP deceleration.Every person has an individual ability to gain weight up to ‘maximum bodyweight’, which indicates the individual potential energy for weight gain. Overweight excessively consumes the body's ‘vital energy’, and devours the body potential energy. Weight loss creates ‘body potential power to weight gain’ that increases physical/mental activity, recovers from disease, or weight regain. The body should consume fewer calories due the decline in MR with age. Conclusions Our findings support that overweight and overeating increase in MR, which delays time-flow perception, accelerates aging, and limits lifespan. Metabolic intoxication should be managed during weight loss. Trial Registration ClinicalTrials.gov NCT06410352 (05/08/2024): https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000EG8K&selectaction=Edit&uid=U0006MBT&ts=56&cx=-vph5l9
The aging process and declining muscle strength and function are known to increase the risk of falls in older adults. The Nintendo Wii Balance Board (NWBB) is a cost-effective and easily accessible alternative to traditional dynamometry for measuring lower limb muscle strength. The study objective was to validate the ability of NWBB to assess lower limb muscle strength and screen the risk of falls in older adults. Ninety community-dwelling elderly women, divided into falling risk and non-falling groups, underwent lower limb muscle strength measurements using NWBB. Moreover, the power index of the sit-to-stand test (PSTS) was calculated from the time to completed Five Times Sit-to-Stand Test (FTSST) (TSTS). The correlation between each variable was assessed. The cut-off score, sensitivity, and specificity for the NWBB's measurement of lower limb muscular strength was determined using the receiver operating curve (ROC). The falling-risk elderly women showed significantly higher TSTS and significantly lower PSTS and leg muscle strength measured by NWBB than the non-falling risk group (p-value < 0.01). A strong negative correlation was observed between TSTS and lower limb muscle strength measured by NWBB (r = - 0.747, p < 0.001). The appropriate cut-off score was > 79.83 kg to identify non-falling risk older adults with the best sensitivity (90.38%) and specificity (86.84%). In conclusion, the NWBB has demonstrated concurrent validity with established measures of lower limb muscle strength, making it a viable option for screening the risk of falls in elderly women populations.
Aging is intricately linked to cognitive decline and neurodegenerative diseases, with neural stem cells (NSCs) playing a crucial role in brain function maintenance and repair. We examine the age-related metabolic shifts in NSCs, such as alterations in mitochondrial dynamics and protein expression, and how these changes affect NSCs’ function of neurogenesis. We discuss the functional decline in NSCs’ proliferation and self-renewal capacity, mainly in the hippocampus, and their implications for cognitive function and emotional regulation. We also highlight the potential of understanding these cellular changes within NSCs to develop novel therapeutic strategies for neurodegenerative diseases and brain injuries, emphasizing the importance of harnessing NSC therapy in aging-related conditions.
Plant secondary metabolites (PSM) including polyphenols, alkaloids, and terpenes are diverse dietary influencers of human health that are also emerging as potent longevity modulators. However, the mechanistic understanding of the anti-ageing effects of PSM vis-à-vis the modern hallmarks of ageing i.e., cellular senescence, chronic inflammation, gut dysbiosis, telomere attrition, genome instability, proteostasis and autophagy, epigenetic alterations, nutrient sensing pathways, and stem cells dysfunctions, is limited. The present work provides a comprehensive review of the extent and depth of PSM as regulators of ageing within the framework of the modern hallmarks of ageing. Current evidence suggests that PSM can influence all known ageing hallmarks albeit to a varying degree. There is immense scope for identifying novel PSM targeting the hallmarks of ageing especially related to cellular senescence (as senolytics), gut microbiome, and epigenetic mechanisms. In addition, PSM and gut dysbiosis are of particular interest due to their mutual bidirectional interactions and amalgamation that could be useful in developing novel anti-ageing functional foods. Future research on the development of PSM-based anti-ageing therapies is recommended to focus on the integrative assessment of the modern hallmarks of ageing for a more holistic approach.
To evaluate the relationship between metformin and the outcome of coronavirus disease 2019 (COVID-19) infection. The study included 413 patients with type 2 diabetes among the 5217 patients enrolled in a COVID-19 study, and analyzed whether receiving metformin therapy prior to infection was associated with risk of ICU admission, development of pneumonia and length of hospital stay. The study also examined the correlation between metformin treatment and levels of IL-6, CRP, serum ferritin (SF), lymphocyte, CD4 at admission, as well as the increase in open reading frame 1ab gene cycle threshold (ORF1abCT) after one week of hospitalization. There were no differences in age, sex, BMI, comorbidities, number of vaccine doses or eGFR between patients receiving and not receiving metformin therapy. In the ICU group, the proportion of patients not receiving metformin was 92.5%, significantly higher than the 69.2% of patients not admitted to ICU (p = 0.010). In the pneumonia group, the proportion of patients not receiving metformin was 78.6%, significantly higher than the 67.2% in the non-pneumonia group (p = 0.020). Compared with patients receiving no treatment, those receiving metformin had a shorter hospital stay (12.1 ± 5.9 days vs. 14.5 ± 8.2 days, p = 0.001). In the patients ≥ 60 years old, those receiving treatment had significantly lower levels of IL-6 (median, 12.3 pg/ml vs. 4.0 pg/ml, p = 0.026) and significantly higher levels of Lymphocyte (median, 1.2 × 109/L vs. 1.4 × 109/L, p = 0.015) compared with those not receiving treatment. However, for the patients under 60, there were no significant differences observed in IL-6 and Lymphocyte levels between those receiving treatment and those not. Metformin can reduce the severity of COVID-19 infection and attenuate the inflammatory response associated with COVID-19 infection.
Erlec1 gene has been suggested to be involved in the regulation of bone development. However, the underlying mechanism remains largely unknown. In this study, we showed that loss of Erlec1 leads to growth retardation in mice. Erlec1-/- mice exhibited increased proliferation, delayed differentiation and mineralization in osteoblasts accompanied by decreased production of collagen I. Our data demonstrated that Erlec1 regulates bone formation through modulating proliferation and differentiation of osteoblasts by affecting the synthesis of collagen I, suggesting that Erlec1 may serve as a potent target for bone metabolism diseases.
Hormesis is a biological phenomenon where exposure to a low dose of a stressor or toxin induces a beneficial adaptive response, whereas higher doses may have detrimental effects. The concept of hormesis is being increasingly appreciated not only in toxicology and in pharmacology, but also in nutrition, clinical medicine, and in situations involving everyday life. Hormesis is an adaptive response of cells and organisms to a moderate and intermittent stressful stimulation. Following such stimulation, the organism must respond, and it has to make a choice: either treat it as a positive ‘challenge’, adapting to it and increasing its robustness, or treat it as a negative ‘threat’ with detrimental consequences for physiology and health. In clinical and everyday situations it is usually difficult to advise patients on how to determine the strength of such stimulation, and when to decide that each new stimulation is too low (ineffective), moderate (appropriate for health), or excessive (damaging to health). In this paper we argue that it is possible to rely on the subjective feelings of ‘comfort vs discomfort’, for deciding about the strength of the stimulus: if each exposure to a stimulation is felt by the individual as a ’comfortable’ event, then it is likely that its effects are beneficial (a hormetic challenge). If it is felt as an ‘uncomfortable’ event, then it is likely that it is damaging to health (a threat). These feelings take place in the anterior insula which evaluates the state of resources for responding to an external or internal event, and are a result of the integration of signals from the amygdala, hippocampus, and the prefrontal cortex. Digital cognitive stimulation and nutritional hormesis are mentioned as two detailed examples.
The role of the endoplasmic reticulum (ER) in aging processes has not attracted much attention of researchers, while this structure plays one of the central roles in the processes of intracellular synthesis. Summarizing the data presented in this review, we can conclude that the number of polysomes is directly related to the production of proteins required by the cell. In turn, polysomes responsible for the production of specialized proteins are associated with the ER of highly differentiated cells. At the same time, proteins necessary for the functioning of cellular infrastructure are translated on free polysomes, which are not associated with the ER. During aging, an increase in the quantity or surface area of ER was also observed in cells, especially in senescent cells. Summarizing these data we can conclude that cell aging is directly related to changes in their ER, which lead to inhibition of the production of proteins necessary for the operation of cellular infrastructure. Therefore, it is possible to distinguish two targets for reducing age-related processes. These should be actions aimed at changing the ratio between ER-bound and free polysomes in favor of the last ones. The second goal is to regulate the amount of ER by enhancing membrane exchange in the cell. Together, these effects will be aimed at preserving the infrastructural base of cells, at least delaying their age-related degradation. As research progresses, unraveling the complex interplay between intracellular membranes and aging holds great promise for developing novel therapeutic strategies to combat age-related diseases and promote longevity.
Glucose has been shown to shorten lifespan in Caenorhabditis elegans. The connection of glucose to stress resistance in C. elegans, however, appears to be complex. We have shown glucose to be protective against heat stress early in adulthood (1-day-old adults), in both wild-type (WT, N2 strain) animals and those with a mutation in the gene encoding the C. elegans insulin receptor, daf-2. The protection conferred by 1 day on high glucose continues in mid-life (7-day-old adults) for daf-2, but not for WT. Mid-life and late-life stress following 7 or 13 days on high glucose shows glucose enrichment to be neutral or detrimental for recovery from heat stress in both strains. These results were also observed for animals exposed to sorbitol instead of glucose, suggesting the osmotic stress conferred by high concentrations of carbohydrate to be the basis of the resistance to heat stress.
The aim of this study was to assess the longitudinal association between lifestyle factors, mental ill-health indicators and activities of daily living (ADL) disability among ageing adults in Thailand. We analyzed the cohort data of participants (5616 in 2015, 3600 in 2017 and 2863 in 2020) over the age of 45 from three consecutive waves of HART (health, age, retirement) in Thailand. ADL disability was assessed with a 4-item ADL scale. In order to evaluate the longitudinal correlation between measurement of lifestyle factors, mental health indicators, and ADL disability between three survey waves, we conducted a Generalized Estimate Equation Analysis (GEE). The proportion of ADL disability increased from 3.8% in 2015 to 7.0% in 2020. In the final GEE logistic regression model, adjusted for various confounding factors, probable depression (aOR: 1.95, 95% CI: 1.47-2.59), self-reported poor mental health (aOR: 1.28, 95% CI: 1.45-2.27), poor quality of life/happiness (aOR: 1.28, 95% CI: 1.03-1.61), loneliness (aOR: 1.66, 95% CI: 1.33-2.08), brain disease/dementia (aOR: 4.84, 95% CI: 2.70-8.67), physical inactivity (aOR: 6.91, 95% CI: 4.41-10.84) and having underweight (AOR: 1.33, 95% CI: 1.00-1.76) were positively associated with ADL disability. Current smoking (aOR: 0.39, 95% CI: 0.24-0.64) was negatively associated with ADL disability.We found that lifestyle factors (physical inactivity and having underweight) and loneliness, poor quality of life/happiness, probable depression, self-reported poor mental health, and brain disease/dementia were associated with ADL disability. Enhancing lifestyle factors relating to physical activity and healthy diet, and screening and treatment of mental ill-health indicators may reduce ADL disability in Thailand.
The history of the discoveries that shaped the current attitudes to the use of antidiabetic biguanides, mainly metformin, as antiaging agents is reviewed. An emphasis is made on the mounting evidence that the diseases of aging including type II diabetes mellitus, the metabolic syndrome, neurodegenerative conditions and cancer that are featured in the clinical trials of metformin are increasingly recognized as those for which physical exercises are effective in risk reduction and therapy enhancement. The known primary molecular targets of metformin map to some of the signaling pathways by which the effects of the two most robust physiological antiaging interventions, i.e. energy consumption increase and calorie intake restriction, are transduced to the cellular and physiological systems implicated in regulating the balance between, on one hand, growth and proliferation and, on the other hand, maintenance and repair. However, metformin and other allegedly antiaging agents can reproduce but partly and in biased ways the effects of the physiological antiaging interventions. In particular, although metformin may help to maintain the current physical conditions, it hampers the gains in physical fitness that are afforded by exercises. These observations should be taken into account in advising metformin to healthy people engaged in increasing their physical fitness by exercises or to patients whose muscular mass is decreased during disease and should be restored thereafter.
