RESUMO
The human lifespan is influenced by various factors, with physical activity being a significant contributor. Despite the clear benefit of exercise on health and longevity, the association between different types of sports and lifespan is yet to be considered. Accordingly, we aimed to study this association in a large international cohort of former athletes using a robust linear regression model. We collected data on athletes from public sources, accumulating a total of 95,210 observations, 95.5% of which were accounted for by males. The dataset represented athletes born between 1862 and 2002 from 183 countries across 44 sports disciplines. We calculated the change in lifespan by measuring the difference in age between athletes and the corresponding reference populations, while accounting for variations caused by sex, year of death, and country. The results revealed that various sports impacted lifespan differently, with male athletes being more likely to experience benefits from sports than female athletes. Among male athletes, pole vaulting and gymnastics were linked to the highest extension in lifespan (8.4 years, 95% CI [6.8, 9.9] and 8.2 years, 95% CI [7.4, 9], respectively), while volleyball and sumo wrestling were the most negatively associated with lifespan (- 5.4 years, 95% CI [- 7, - 3.8]; - 9.8 years, 95% CI [- 11, - 8.6], respectively). The association between lifespan and popular team sports in males was positive for cricket, rowing, baseball, water polo, Australian rules, hurling, lacrosse, field hockey, minimal for rugby, canoeing and kayaking, basketball, gridiron football, and football (soccer), and negative for handball and volleyball. Racquet sports (i.e., tennis and badminton) exhibited a consistent and positive association in both male and female athletes, as shown by an extended lifespan of up to 5.7 years in males (95% CI [5, 6.5]) and 2.8 years in females (95% CI [1.8, 3.9]). Although lacking conclusive evidence, we theorize that the observed results may be attributed to the aerobic and anaerobic characteristics of each sport, with mixed sports yielding the maximum benefits for the lifespan. While results from female athletes should be cautiously interpreted, our study highlights the complex interplay between sports and lifespan and contributes to the growing body of knowledge on the multifaceted relationship between physical activity and human longevity.
RESUMO
Excessive amounts of reactive oxygen species (ROS) lead to macromolecular damage and high levels of cell death with consequent pathological sequelae. We hypothesized that switching cell death to a tissue regenerative state could potentially improve the short-term and long-term detrimental effects of ROS-associated acute tissue injury, although the mechanisms regulating oxidative stress-induced cell fate decisions and their manipulation for improving repair are poorly understood. Here, we show that cells exposed to high oxidative stress enter a poly (ADP-ribose) polymerase 1 (PARP1)-mediated regulated cell death, and that blocking PARP1 activation promotes conversion of cell death into senescence (CODIS). We demonstrate that this conversion depends on reducing mitochondrial Ca2+ overload as a consequence of retaining the hexokinase II on mitochondria. In a mouse model of kidney ischemia-reperfusion damage, PARP inhibition reduces necrosis and increases transient senescence at the injury site, alongside improved recovery from damage. Together, these data provide evidence that converting cell death into transient senescence can therapeutically benefit tissue regeneration.
Assuntos
Morte Celular , Senescência Celular , Estresse Oxidativo , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases , Animais , Estresse Oxidativo/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Camundongos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Morte Celular/efeitos dos fármacos , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Cálcio/metabolismo , Modelos Animais de DoençasRESUMO
Evidence supports the notion that metabolic pathways are major regulators of organismal aging, and that metabolic perturbations can extend health- and lifespan. For this reason, dietary interventions and compounds perturbing metabolism are currently explored as anti-aging strategies. A common target for metabolic interventions delaying aging is cellular senescence, a state of stable growth arrest that is accompanied by various structural and functional changes including the activation of a pro-inflammatory secretome. Here, we summarize the current knowledge on the molecular and cellular events associated with carbohydrate, lipid and protein metabolism, and define how macronutrients can regulate induction or prevention of cellular senescence. We discuss how various dietary interventions can achieve prevention of disease and extension of healthy longevity by partially modulating senescence-associated phenotypes. We also emphasize the importance of developing personalized nutritional interventions that take into account the current health and age status of the individual.
Assuntos
Senescência Celular , Longevidade , Senescência Celular/genética , NutrientesRESUMO
Dietary choices have a profound impact on the aging process. In addition to the total amount of energy intake, macronutrient composition influences both health and lifespan. However, the exact mechanisms by which dietary macronutrients influence onset and progression of age-associated features remain poorly understood. Cellular senescence is a state of stable growth arrest characterized by the secretion of numerous bioactive molecules with pro-inflammatory properties. Accumulation of senescent cells is considered one of the basic mechanisms of aging and an important contributor to chronic inflammation and tissue degeneration. Whether dietary macronutrients affect the accumulation and the phenotype of senescent cells with age is still unknown. Here, we show that feeding on diets with varying ratios of dietary macronutrients for 3 months has a significant effect on different senescence-associated markers in the mouse liver. High protein intake is associated with higher expression levels of the two classical senescence-associated growth arrest genes, p21 and p16. Furthermore, the expression of many pro-inflammatory secretory markers was increased in diets enriched in protein and further enhanced by increases in fat content. These results provide preliminary evidence that dietary macronutrients have a significant influence on senescence markers and merit further investigation.
Assuntos
Envelhecimento , Senescência Celular , Animais , Camundongos , Envelhecimento/genética , Envelhecimento/metabolismo , Senescência Celular/genética , Fenótipo , Proteínas Alimentares/farmacologia , FígadoRESUMO
Cellular senescence constitutes a generally irreversible proliferation barrier, accompanied by macromolecular damage and metabolic rewiring. Several senescence types have been identified based on the initiating stimulus, such as replicative (RS), stress-induced (SIS) and oncogene-induced senescence (OIS). These senescence subtypes are heterogeneous and often develop subset-specific phenotypes. Reduced protein synthesis is considered a senescence hallmark, but whether this trait pertains to various senescence subtypes and if distinct molecular mechanisms are involved remain largely unknown. Here, we analyze large published or experimentally produced RNA-seq and Ribo-seq datasets to determine whether major translation-regulating entities such as ribosome stalling, the presence of uORFs/dORFs and IRES elements may differentially contribute to translation deficiency in senescence subsets. We show that translation-regulating mechanisms may not be directly relevant to RS, however uORFs are significantly enriched in SIS. Interestingly, ribosome stalling, uORF/dORF patterns and IRES elements comprise predominant mechanisms upon OIS, strongly correlating with Notch pathway activation. Our study provides for the first time evidence that major translation dysregulation mechanisms/patterns occur during cellular senescence, but at different rates depending on the stimulus type. The degree at which those mechanisms accumulate directly correlates with translation deficiency levels. Our thorough analysis contributes to elucidating crucial and so far unknown differences in the translation machinery between senescence subsets.