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Background Chat Generative Pre-trained Transformer (ChatGPT) and other ChatBots have emerged as tools for interacting with information in manners resembling natural human speech. Consequently, the technology is used across various disciplines, including business, education, and even in biomedical sciences. There is a need to better understand how ChatGPT can be used to advance gerontology research. Therefore, we evaluated ChatGPT responses to questions on specific topics in gerontology research, and brainstormed recommendations for its use in the field. Methods We conducted semistructured brainstorming sessions to identify uses of ChatGPT in gerontology research. We divided a team of multidisciplinary researchers into 4 topical groups: (a) gero-clinical science, (b) basic geroscience, (c) informatics as it relates to electronic health records, and (d) gero-technology. Each group prompted ChatGPT on a theory-, methods-, and interpretation-based question and rated responses for accuracy and completeness based on standardized scales. Results ChatGPT responses were rated by all groups as generally accurate. However, the completeness of responses was rated lower, except by members of the informatics group, who rated responses as highly comprehensive. Conclusions ChatGPT accurately depicts some major concepts in gerontological research. However, researchers have an important role in critically appraising the completeness of its responses. Having a single generalized resource like ChatGPT may help summarize the preponderance of evidence in the field to identify gaps in knowledge and promote cross-disciplinary collaboration. [ABSTRACT FROM AUTHOR]

Studies in mice and cross-sectional studies in humans support the premise that cellular senescence is a contributing mechanism to age-associated deficits in physical function. We tested the hypotheses that circulating proteins secreted by senescent cells are (i) associated with the incidence of major mobility disability (MMD), the development of persistent mobility disability (PMMD), and decrements in physical functioning in older adults, and (ii) influenced by physical activity (PA). Using samples and data obtained longitudinally from the Lifestyle Interventions in Elders Study clinical trial, we measured a panel of 27 proteins secreted by senescent cells. Among 1 377 women and men randomized to either a structured PA intervention or a healthy aging (HA) intervention, we observed significant associations between several senescence biomarkers, most distinctly vascular endothelial growth factor A (VEGFA), tumor necrosis factor receptor 1 (TNFR1), and matrix metallopeptidase 7 (MMP7), and the onset of both MMD and PMMD. Moreover, VEGFA, GDF15, osteopontin, and other senescence biomarkers were associated with reductions in short physical performance battery scores. The change in senescence biomarkers did not differ between PA and HA participants. In the whole cohort, higher levels of PA were associated with significantly greater reductions in 10 senescence-related proteins at 12 and/or 24 months. These data reinforce cellular senescence as a contributing mechanism of age-associated functional decline and the potential for PA to attenuate this hallmark of aging. Clinical Trials Registration Number: NCT01072500 [ABSTRACT FROM AUTHOR]

Background: Hospital deaths after sepsis have decreased substantially and most young adult survivors rapidly recover (RAP). However, many older survivors develop chronic critical illness (CCI) with poor long-term outcomes. The etiology of CCI is multifactorial and the relative importance remains unclear. Sepsis is caused by a dysregulated immune response and biomarkers reflecting a persistent inflammation, immunosuppression, and catabolism syndrome (PICS) have been observed in CCI after sepsis. Therefore, the purpose of this study was to compare serial PICS biomarkers in (i) older (vs young) adults and (ii) older CCI (vs older RAP) patients to gain insight into underlying pathobiology of CCI in older adults.Method: Prospective longitudinal study with young (≤45 years) and older (≥65 years) septic adults, who were characterized by (i) baseline predisposition, (ii) hospital outcomes, (iii) serial Sequential Organ Failure Assessment (SOFA) organ dysfunction scores over 14 days, (iv) Zubrod Performance status at 3-, 6-, and 12-month follow-up, and (v) mortality over 12 months, was conducted. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS.Results: Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status, and mortality over 12 months. Additionally, older (vs young) and older CCI (vs older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism, and antiangiogenesis over 14 days after sepsis.Conclusion: Older (vs young) and older CCI (vs older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS. [ABSTRACT FROM AUTHOR]

Background: Low-grade chronic inflammation, characterized by elevations in plasma Interleukin-6 (IL-6), is an independent risk factor of impaired mobility in older persons. Angiotensin receptor blockers and omega-3 polyunsaturated fatty acids (ω-3) may reduce IL-6 and may potentially improve physical function. To assess the main effects of the angiotensin receptor blocker losartan and ω-3 as fish oil on IL-6 and 400 m walking speed, we conducted the ENRGISE Pilot multicenter randomized clinical trial.Methods: The ENRGISE Pilot enrolled participants between April 2016 and June 2017, who participated for 12 months. Participants were aged ≥70 years with mobility impairment, had IL-6 between 2.5 and 30 pg/mL, and were able to walk 400 m at baseline. Participants were randomized in three strata 2 × 2 factorial to: (i) losartan 50-100 mg/d or placebo (n = 43), (ii) fish oil 1,400-2,800 mg/d or placebo (n = 180), and (iii) with both (n = 66).Results: Two hundred eighty-nine participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). There was no effect of losartan (difference of means = -0.065 ± 0.116 [SE], 95% confidence interval [CI]: -0.293-0.163, p = .58) or fish oil (-0.020 ± 0.077, 95% CI: -0.171-0.132, p = .80) on the log of IL-6. Similarly, there was no effect of losartan (-0.025 ± 0.026, 95% CI: -0.076-0.026, p = .34) or fish oil (0.010 ± 0.017, 95% CI: -0.025-0.044, p = .58) on walking speed (m/s).Conclusions: These results do not support the use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation.Registration: Clinicaltrials.gov NCT02676466. [ABSTRACT FROM AUTHOR]

Background. Lower ambulatory performance with aging may be related to a reduced oxidative capacity within skeletal muscle. This study examined the associations between skeletal muscle mitochondrial capacity and efficiency with walking performance in a group of older adults. Methods. Thirty-seven older adults (mean age 78 years; 21 men and 16 women) completed an aerobic capacity (VO2 peak) test and measurement of preferred walking speed over 400 m. Maximal coupled (State 3; St3) mitochondrial respiration was determined by high-resolution respirometry in saponin-permeabilized myofibers obtained from percutanous biopsies of vastus lateralis (n = 22). Maximal phosphorylation capacity (ATPmax) of vastus lateralis was determined in vivo by 31P magnetic resonance spectroscopy (n = 30). Quadriceps contractile volume was determined by magnetic resonance imaging. Mitochondrial efficiency (max ATP production/max O2 consumption) was characterized using ATPmax per St3 respiration (ATPmax/St3). Results. In vitro St3 respiration was significantly correlated with in vivo ATPmax (r2 = .47, p = .004). Total oxidative capacity of the quadriceps (St3*quadriceps contractile volume) was a determinant of VO2 peak (r2 = .33, p = .006). ATPmax (r2 = .158, p = .03) and VO2 peak (r2 = .475, p < .0001) were correlated with preferred walking speed. Inclusion of both ATPmax/St3 and VO2 peak in a multiple linear regression model improved the prediction of preferred walking speed (r2 = .647, p < .0001), suggesting that mitochondrial efficiency is an important determinant for preferred walking speed. Conclusions. Lower mitochondrial capacity and efficiency were both associated with slower walking speed within a group of older participants with a wide range of function. In addition to aerobic capacity, lower mitochondrial capacity and efficiency likely play roles in slowing gait speed with age. [ABSTRACT FROM PUBLISHER]

Caloric restriction and physical exercise have proven beneficial against age-associated changes in body composition and declining physical performance; however, little is known regarding what benefit these interventions might have when initiated late in life. The study of mimetics of diet and exercise and the combination thereof may provide additional treatments for a vulnerable elderly population; however, how and when to initiate such interventions requires consideration in developing the most safe and efficacious treatment strategies. In this review, we focus on preclinical late-life intervention studies, which assess the relationship between physical function, sarcopenia, and body composition. We provide a conceptual framework for the ever-changing definition of sarcopenia and a rationale for the use of an appropriate rodent model of this condition. We finish by providing our perspective regarding the implications of this body of work and future areas of research that may also contribute to the ultimate goal of extending healthspan. [ABSTRACT FROM PUBLISHER]

Mitochondrial biogenesis is essential for cell viability. Growth hormone receptor knockout (GHRKO), calorie restriction, and surgical visceral fat removal constitute experimental interventions to delay aging and increase life span. We examined the expression of known regulators of mitochondriogenesis: peroxisome proliferator–activated receptor γ co-activator 1α (PGC-1α), adenosine monophosphate (AMP)–activated protein kinase (AMPK), sirtuin-1 (SIRT-1) and sirtuin-3 (SIRT-3), endothelial nitric oxide synthase (eNOS), nuclear respiratory factor-1, mitochondrial transcription factor A (TFAM), and mitofusin-2 (MFN-2) in the skeletal muscles and hearts of control and calorie-restricted female GHRKO mice and in the kidneys of male GHRKOs after visceral fat removal or sham surgery. Expression of PGC-1α in skeletal muscles, AMPK, SIRT-1, SIRT-3, eNOS, and MFN-2 in the heart and PGC-1α, AMPK, SIRT-3, eNOS, and MFN-2 in kidneys was increased in GHRKO mice but was not affected by calorie restriction or visceral fat removal. GHRKO mice have increased expression of key regulators of mitochondriogenesis, which is not improved further by calorie restriction or visceral fat removal. [ABSTRACT FROM PUBLISHER]

Background.: Nuclear factor kappa B (NF-κB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. Methods. The present study examined lean mass, maximal force production, and skeletal muscle NF-kB signaling in 41 men categorized as sedentary (OS, N- 13,63.85 ±6.59 year), physically active (OA,N- 14,60.71 ±5.54 year), or young and sedentary

Background: Elevated systemic levels of myeloperoxidase (MPO) have been associated with unfavourable clinical outcomes. In the present study, we evaluate the impact of MPO, a pro-oxidant enzyme that catalyzes the initiation of lipid peroxidation and affects nitric oxide levels, on the risk of all-cause mortality in a large population of frail octogenarians and nonagenarians living in community. Methods. We analyzed data from the Aging and Longevity Study in the Sirente Geographic Area (ilSIRENTE Study), a prospective cohort study that collected data on all individuals aged 80 years and older living in a mountain community (n = 363). The main outcome measure was the risk of death after 4 years of follow-up. Participants were divided into three groups based on MPO tertiles: lower tertile ≤ 61.5 mg/L (n = 120), intermediate tertile 61.6–140.6 mg/L (n = 120), and higher tertile ≥140.7 mg/L (n = 123). Results. A total of 150 deaths occurred during 4-years follow-up. The mean MPO level was 170.8 ± 177.5 mg/L among those who died compared with 135.4 ± 142.4 mg/L among survivors (p = .03). Individuals in the highest MPO tertile had higher risk of mortality (40% [60/123]) compared with those in the lower tertile (26% [39/120]). After adjusting for potential confounders, compared with participants in the lower tertile, those in the higher tertile had a hazard ratio for mortality of 1.97 (95% confidence interval: 1.02–3.80). Conclusion. Our results obtained from a representative sample of very old and frail elderly individuals expand the knowledge that low levels of MPO are associated with better survival. [ABSTRACT FROM PUBLISHER]

Controversy exists as to whether lifelong 40% calorie restriction (CR) enhances, has no effect on, or disrupts cognitive function during aging. Here, we report the effects of CR versus ad-lib feeding on cognitive function in male Brown Norway x Fisher344 rats across a range of ages (8-38 months), using two tasks that are differentially sensitive to age-related cognitive decline: object recognition and Morris water maze (MWM). All ages performed equally in object recognition, whereas, as a group, CR rats were impaired. In contrast, there was an age-related impairment in the MWM that was attenuated by CR as measured by time in proximity with and latency to reach the platform. Distance to the platform, a more sensitive measure, was not affected by CR. Finally, CR resulted in an overall increase in physical activity, one of several behavioral confounders to consider in the interpretation of cognitive outcomes in both tasks. [ABSTRACT FROM AUTHOR]

Chronic inflammation is associated with the aging process and numerous age-related pathologies, We evaluated the effects of age, caloric restriction (CR), and exercise on plasma C-reactive protein (CRP), interleukin-6, and total antioxidant capacity in Fisher 344 rats. The inflammatory markers were analyzed using enzyme-linked immunosorbent assays (ELISA), while total antioxidant potential was determined by a spectrophotometric method. An increase in circulating levels of CRP with age was attenuated with long-term 40% CR; short-term 40% CR in young animals also reduced CRP concentration compared to age-matched controls. Lifelong exercise with 8% CR showed a marked decrease in CRP levels compared to 8% CR controls and an even greater reduction compared to ad libitum-fed rats. Plasma interleukin-6 levels remained unchanged with age, CR, and exercise, whereas inflammation levels showed an inverse association with plasma antioxidant status. These studies highlight the anti-inflammatory effects of CR and exercise. [ABSTRACT FROM AUTHOR]

Apoptosis research is a rapidly developing area, but the role of apoptosis is still unclear and controversial. For example, several studies document a significant loss of cardiac and skeletal myocytes during normal aging, possibly by apoptotic mechanisms. This loss in cells may be directly mediated by mitochondrial dysfunction caused by chronic exposure to oxidants and increased activation of mitochondrial permeability transition pores. This review will discuss apoptosis in the context of normal aging of T cells, cardiac myocytes, skeletal muscle, and brain cortex. Particular attention is paid to the role of the mitochondria, because they have been implicated as a major control center regulating apoptosis. Mitochondrial oxidative stress and a decline in mitochondrial energy production in vitro often leads to activation of apoptotic pathways, but whether this occurs in vivo is unclear. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy and the loss of myofibers contribute to sarcopenia, a condition associated with normal aging. However, relatively little is known regarding the relevance of apoptosis to skeletal muscle homeostasis and the possible mechanisms involved, although evidence suggests that apoptosis may play a role during muscle aging. By age 80 it is estimated that humans generally lose 30%-40% of skeletal muscle fibers, particularly from muscles containing type II fibers such as the vastus lateralis muscle. Studies using rodents show that between a 20%-50% loss in muscle fibers occurs depending on the specific fiber type studied. Caspases (cysteine-dependent, aspartate-specific proteases) such as caspase-3 play an important role in mediating cell death in that many of the apoptotic signaling pathways, such as the mitochondrial-mediated, receptor-mediated, and sarcoplasmic-reticulum-mediated pathways, converge at caspase-3 in the caspase cascade. Studies show that with age the levels of several caspases are significantly increased. Therefore, the activation of these proteolytic caspases may be partly responsible for the initiation of muscle protein degradation, loss of muscle nuclei, which is associated with local atrophy, and finally into cell death of the myocyte. [ABSTRACT FROM AUTHOR]