Scarch For Lifestyle Factors Preventing Long-Lived Individuals From Frailty

Background:Old age is often accompanied by the emergence of geriatric syndromes,such as frailty,that is presented by a physiological decline resulting in increased susceptibility to poor health outcomes and death.On the other hand,long-lived individuals including nonagenarians and centenarians walk into their late-life stages in good health with a lower prevalence of common age-related diseases,therefore,present an excellent model of successful aging.The lifestyle factors that protect long-lived individuals from frailty remain largely unknown.The current study aims to uncover the lifetime habits preventing frailty at the late-life stages in a cohort of long-lived individuals.Methods and Results:This study involved a total of 113,000 participants with 26,800 nonagenarians and 19,500 centenarians pooled from the large cohort of the Chinese Longitudinal Healthy Longevity Survey（CLHLS,1998–2018）.Inclusion criteria included ethnicity（Han Chinese）and age（≥90）,while cases were dropped based on strict exclusion criteria;that is missing any variable for frailty Index（FI）estimation or the lifestyle factors studied in this thesis.A total of 9277 long-lived individuals aged between 90–115 with mean age±standard deviation（SD）=96.88±4.74 including 66%（n=6091）females and 34%（n=3186）males were included in the study.The study population consisted of 5576 nonagenarians（mean age±SD=93.63±2.82）and 3701 centenarians（mean age±SD=101.78±2.06）.Frailty is assessed through various methods including deficit-accumulation-based Frailty Index（FI）,Fried’s Frailty Phenotype,FRAIL score,Edmonton Frail Scale（EFS）,and so on.FI is estimated as the ratio of the number of deficits present in an individual to the total 31 deficit variables from five domains of frailty including socio-psychological vulnerability,cognitive impairment,functional independence,geriatric disabilities,and general health status.Compared to other methods of frailty estimation,FI provides a more comprehensive and systematic estimation of frailty,therefore,FI was used in this thesis.The study population was categorized into frailty categories according the pre-defined 6-point scale based on FI;Robust（FI=0.00–0.09）,Pre-Frail1（FI=0.10–0.19）,Pre-Frail 2（FI=0.20–0.29）,Mildly Frail（FI=0.30–0.39）,Moderately Frail（FI=0.40–0.49）,and Severely Frail（FI≥0.50）.In order to evaluate the quantitative effects of lifestyle factors on frailty in the long-lived individuals（aged≥90）,first,lifestyle preferences were decoded into three-dosage ordinals ranging from low to high（rare,occasional,frequent）.Subsequently,three logistic regression models were used in this thesis:model 1（unifactorial）,model 2（multifactorial;adjusted for uncontrollable factors;age and gender）,and model 3（multifactorial;model 2 further adjusted for controllable lifestyle factors）to evaluate the effect of lifestyle factors on frailty.Eventually,centenarians were subjected to sensitivity analysis to evaluate and validate the effects of lifestyle preferences in the extreme longevity cohort.The findings are as follows:The FI in the study population showed a skewed distribution with a mean score±SD=0.15±0.10.The maximum FI observed was 0.69 and the 99^th percentile was0.48.In relation to age,the slope of deficit accumulation in the study population was0.018 with 95%confidence interval（CI）of 0.016–0.019.Based on FI,the population was classified as 39%Robust,35%Pre-Frail 1,16%Pre-Frail 2,7%Mildly Frail,2%Moderately Frail,and 1%Severely Frail.Female population was more prone to age-associated frailty（Mildly Frail=9%;Moderately Frail=3%;Severely Frail=1%）as compared to male counterparts（Mildly Frail=4%;Moderately Frail=2%;Severely Frail=1%）.Among the psychological factors,"good"quality of life,a measure of psychological satisfaction,was associated with significantly reduced odds of frailty at late-life stages[Odds Ratio（95%Confidence Interval）=0.34（0.28–0.41）,p<0.001].Similarly,the constructs of positive attitude,"always"looking at the bright side and"always"living as happy as when were young,were also associated with significantly reduced odds of frailty at late-life stages in long-lived individuals[0.30（0.25–0.36）,p<0.001)and(0.47（0.40–0.55）,p<0.001],respectively."Good"quality of life,and"always"looking at the bright side and living as happy as when were young were consistently validated in the following sensitivity analysis,implying their critical role in reducing the odds of frailty in a degree-dependent manner."Occasional fruits consumption"was associated to reduced odds of frailty in unifactorial model[0.80（0.73–0.88）,p<0.001]and multifactorial model[0.80（0.73–0.87）,p<0.001],while lost its significance when further adjusted for controllable lifestyle preferences[0.98（0.89–1.08）,p=0.680].On the other hand,vegetables consumption dosage-dependently reduced the odds of frailty across all the models[Frequent consumption:model 1:0.45（0.37–0.54）,p<0.001;model 2:0.48（0.39–0.57）,p<0.001;model 3 0.55（0.45–0.67）,p<0.001;Occasional consumption:model 1:0.61（0.50–0.75）,p<0.001,model 2:0.63（0.51–0.78）,p<0.001;model 3:0.72（0.59–0.90）,p=0.003].These findings were validated in the subsequent sensitivity analysis."Occasional consumption of meat"was associated with reduced odds of frailty in the long-lived individuals compared to the"rare or no consumption"across all the models[model 1:0.81（0.75–0.88）,p<0.001;model 2:0.90（0.82–0.97）,p=0.008;model 3:0.85（0.76–0.95）,p=0.004]."Frequent eggs consumption"was associated to increased odds of frailty in the multifactorial models[1.14（1.00–1.30）,p=0.053and 1.48（1.25–1.75）,p<0.001],while"occasional consumption of eggs"was associated with significantly reduced odds of frailty[0.87（0.80–0.94）,p=0.001]in a unifactorial analysis and almost reached significance in the multifactorial model[0.92（0.84–1.00）,p=0.059]."Frequent sugar consumption"was associated with significantly increased odds of frailty at late-life stages in a multifactorial model[1.17（1.01–1.36）,p=0.035],while"occasional consumption of sugar"was associated with reduced odds of frailty[0.90（0.82–0.98）,p=0.017].Thus,meat,eggs,and sugar affect frailty following a characteristic goldilocks principle i.e.,a moderate consumption presented beneficial effects compared to frequent or rare.Similar findings were observed in the subsequent sensitivity analysis."Frequent intake of tea and garlic consumption"were also associated to significantly reduced odds of frailty at late-life stages in long-lived individuals[0.89（0.80–0.98）,p=0.028 and 0.88（0.77–1.00）,p=0.048],respectively.These associations were also validated in the sensitivity analysis.Physically active individuals were at significantly lower risk of frailty at late-life stages as compared to the inert individuals."Leisure-time exercise"was associated to significantly reduced odds of frailty in the study population[0.91（0.83–0.99）,p=0.037].Similarly,individuals with physical labor as their profession were also at a significantly lower risk of frailty at late-life stages[0.75（0.68–0.83）,p<0.001].These findings were validated in the sensitivity analysis.Conclusions and Discussion:In summary,lifestyle preferences including psychological and nutritional factors,and physical activity quantitatively affect frailty at the late-life stages.Psychological satisfaction and positive attitude showed the most profound reduction in frailty,followed by frequent vegetable consumption and physical activity.Vegetables,garlic,and tea consumption significantly reduced the odds of frailty in a dosage-dependent manner,while meat,eggs,and sugar affected frailty based on Goldilocks principle.Collectively,these findings imply that healthy longevity is the payback of life-long lifestyle preferences and propose that robust adulthood and independent old age can be attained through quantitative interventions in lifestyle.Therefore,self-control（an ability to regulate emotions,thoughts,and behavior despite the temptations,impulses,and situations）and self-discipline（an ability to stick to a healthy lifestyle including eating preferences and being physically active even without a desire）may prove to be the essential means to achieve this balance.This thesis explored a wide range of lifestyle preferences for their impact on the health status at late-life stages and made a significant contribution to the scientific research by expanding the current knowledge base regarding the role of lifetime habits in preventing age-associated frailty.In the future,clinicians and geriatricians could potentially decrease the risk of frailty in the elderly population by recommending quantitative interventions in lifestyle.