scholarly journals Body Clock: Matching Personalized Multimorbidity and Fast Aging Using Information Entropy

Author(s):  
Shabnam Salimi ◽  
Ali Vehtari ◽  
Marcel Salive ◽  
Luigi Ferrucci

With aging, most older adults are at risk of having more than two diseases, conventionally defined as multimorbidity. We determined body organ disease number (BODN) as a new multimorbidity index. We measured the degree to which each disease level, from mild to severe, predicts longitudinal BODN uncoupled from chronological age. We determined Body Clock using global disease levels burden from all systems predicting longitudinal BODN for each individual, which is a proxy of the personalized rate of biological aging. Change in Body Clock predicts late-life age-related outcomes and can be used for geriatric clinics and clinical trials for precision medicine.

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S479-S479
Author(s):  
Waylon J Hastings ◽  
Daniel Belsky ◽  
Idan Shalev

Abstract Biological processes of aging are thought to be modifiable causes of many chronic diseases. Measures of biological aging could provide sensitive endpoints for studies of risk factors hypothesized to shorten healthy lifespan and/or interventions that extend it. However, uncertainty remains about how to measure biological aging and if proposed measures assess the same thing. We tested four proposed measures of biological aging with available data from NHANES 1999-2002: Klemera-Doubal method (KDM) Biological Age, homeostatic dysregulation, Levine Method (LM) Biological Age, and leukocyte telomere length. All measures of biological aging were correlated with chronological age. KDM Biological Age, homeostatic dysregulation, and LM Biological Age were all significantly associated with each other, but were each not associated with telomere length. NHANES participants with older biological ages performed worse on tests of physical, cognitive, perceptual, and subjective functions known to decline with advancing chronological age and thought to mediate age-related disability. Further, NHANES participants with higher levels of exposure to life-course risk factors were measured as having older biological ages. In both sets of analyses, effect-sizes tended to be larger for KDM Biological Age, homeostatic dysregulation, and LM Biological Age as compared to telomere length. Composite measures combining cellular- and patient-level information tended to have the largest effect-sizes. The cellular-level aging biomarker telomere length may measure different aspects of the aging process relative to the patient-level physiological measures. Studies aiming to test if risk factors accelerate aging or if interventions may slow aging should not treat proposed measures of biological aging as interchangeable.


Author(s):  
Pavanello ◽  
Campisi ◽  
Tona ◽  
Lin ◽  
Iliceto

DNA methylation (DNAm) is an emerging estimator of biological aging, i.e., the often-defined “epigenetic clock”, with a unique accuracy for chronological age estimation (DNAmAge). In this pilot longitudinal study, we examine the hypothesis that intensive relaxing training of 60 days in patients after myocardial infarction and in healthy subjects may influence leucocyte DNAmAge by turning back the epigenetic clock. Moreover, we compare DNAmAge with another mechanism of biological age, leucocyte telomere length (LTL) and telomerase. DNAmAge is reduced after training in healthy subjects (p = 0.053), but not in patients. LTL is preserved after intervention in healthy subjects, while it continues to decrease in patients (p = 0.051). The conventional negative correlation between LTL and chronological age becomes positive after training in both patients (p < 0.01) and healthy subjects (p < 0.05). In our subjects, DNAmAge is not associated with LTL. Our findings would suggest that intensive relaxing practices influence different aging molecular mechanisms, i.e., DNAmAge and LTL, with a rejuvenating effect. Our study reveals that DNAmAge may represent an accurate tool to measure the effectiveness of lifestyle-based interventions in the prevention of age-related diseases.


2019 ◽  
Author(s):  
Anil P.S. Ori ◽  
Loes M. Olde Loohuis ◽  
Jerry Guintivano ◽  
Eilis Hannon ◽  
Emma Dempster ◽  
...  

AbstractSchizophrenia (SCZ) is a severe mental illness that is associated with an increased prevalence of age-related disability and morbidity compared to the general population. An accelerated aging process has therefore been hypothesized as a component of the SCZ disease trajectory. Here, we investigated differential aging using three DNA methylation (DNAm) clocks (i.e. Hannum, Horvath, Levine) in a multi-cohort SCZ whole blood sample consisting of 1,100 SCZ cases and 1,200 controls. It is known that all three DNAm clocks are highly predictive of chronological age and capture different features of biological aging. We found that blood-based DNAm aging is significantly altered in SCZ with age- and sexspecific effects that differ between clocks and map to distinct chronological age windows. Most notably, the predicted phenotypic age (Levine clock) in female cases, starting at age 36 and beyond, is 3.21 years older compared to matching control subjects (95% CI: 1.92-4.50, P=1.3e-06) explaining 7.7% of the variance in disease status. Female cases with high SCZ polygenic risk scores present the highest age acceleration in this age group with +7.03 years (95% CI: 3.87-10.18, P=1.7E-05). Since increased phenotypic age is associated with increased risk of all-cause mortality, our findings suggests that specific and identifiable patient groups are at increased mortality risk as measured by the Levine clock. These results provide new biological insights into the aging landscape of SCZ with age- and sexspecific effects and warrant further investigations into the potential of DNAm clocks as clinical biomarkers that may help with disease management in schizophrenia.


Author(s):  
Chia-Ling Kuo ◽  
Luke C. Pilling ◽  
Janice L Atkins ◽  
Jane AH Masoli ◽  
João Delgado ◽  
...  

AbstractWith no known treatments or vaccine, COVID-19 presents a major threat, particularly to older adults, who account for the majority of severe illness and deaths. The age-related susceptibility is partly explained by increased comorbidities including dementia and type II diabetes [1]. While it is unclear why these diseases predispose risk, we hypothesize that increased biological age, rather than chronological age, may be driving disease-related trends in COVID-19 severity with age. To test this hypothesis, we applied our previously validated biological age measure (PhenoAge) [2] composed of chronological age and nine clinical chemistry biomarkers to data of 347,751 participants from a large community cohort in the United Kingdom (UK Biobank), recruited between 2006 and 2010. Other data included disease diagnoses (to 2017), mortality data (to 2020), and the UK national COVID-19 test results (to May 31, 2020) [3]. Accelerated aging 10-14 years prior to the start of the COVID-19 pandemic was associated with test positivity (OR=1.15 per 5-year acceleration, 95% CI: 1.08 to 1.21, p=3.2×10−6) and all-cause mortality with test-confirmed COVID-19 (OR=1.25, per 5-year acceleration, 95% CI: 1.09 to 1.44, p=0.002) after adjustment for demographics including current chronological age and pre-existing diseases or conditions. The corresponding areas under the curves were 0.669 and 0.803, respectively. Biological aging, as captured by PhenoAge, is a better predictor of COVID-19 severity than chronological age, and may inform risk stratification initiatives, while also elucidating possible underlying mechanisms, particularly those related to inflammaging.


2017 ◽  
Author(s):  
Dilip Jeste ◽  
Jeanne Maglione

The number of older adults in our society is increasing rapidly. Aging is complex and may occur at varying rates across multiple domains, including biological aging, cognitive aging, and emotional aging. Age-related medical conditions are now among the leading causes of morbidity and mortality among older adults, making healthy aging a major public health priority. Successful aging encompasses more than longevity, medical health, or freedom from disability. It can be viewed as a multidimensional construct including minimization of disability and medical illness combined with maximization of physical, cognitive, emotional, and social functioning. We review the current literature regarding successful aging. We also discuss strategies to improve the likelihood of successful aging and several key advances, such as definitions of successful aging in different populations, neuroplasticity of aging, wisdom as an empirical construct, the concept of a good (or successful) death, and the development of age-friendly communities.  This review contains 3 figures, 5 tables, and 53 references. Key words: aging, elderly, older adult, successful aging, successful aging interventions


2021 ◽  
pp. 002203452110379
Author(s):  
G. Baima ◽  
M. Romandini ◽  
F. Citterio ◽  
F. Romano ◽  
M. Aimetti

As the whole world is epidemically aging, the burden of periodontitis and tooth loss is becoming a major health concern. Growing meta-epidemiological data implicate chronic systemic inflammation/infection due to periodontitis as an independent risk factor for aging-related diseases and mortality. However, because people age differently, chronological age is not a reliable marker of an individual’s functional status. Recent advances in geroscience have shown that various biomarker signatures of biological aging are longitudinally associated with declined physical function, morbidity, and mortality due to major age-related diseases, including periodontitis. Here, we emphasize novel research developments bidirectionally linking periodontitis to accelerated biological aging. Using a composite biomarker age estimator, a striking increase in periodontitis and tooth loss was observed in subjects whose biological age at baseline was higher than their chronological age. Moreover, significantly shortened telomeres were encountered in populations affected by severe periodontitis. Second, we elucidate the cellular and molecular pillars of the aging process at the periodontal level. Accumulating evidence suggests that cellular senescence, stem cell exhaustion, and immunoaging are hallmarks of biological aging implicated in the impairment of periodontal homeostasis and the pathophysiology of periodontitis. Indeed, persistent bacteria-derived lipopolysaccharide stimulation influences cellular senescence in osteocytes, driving alveolar bone resorption. Moreover, inflammaging status induced by chronic hyperglycemia elevates the burden of senescent cells in gingival tissues, impairing their barrier function. Lastly, we reviewed a recent breakthrough in senotherapy to directly target the mechanisms of aging at the periodontal level. Physical exercise and intermittent fasting, together with natural compounds, senolytic drugs, and cell therapy, are increasingly being evaluated to rejuvenate the oral cavity. Following these innovations in geroscience, further advancements could provide oral clinicians the chance to intercept biological aging when still “subclinical” and set interventions for halting or delaying the trajectory toward aging-related diseases while patients are still chronologically young.


2020 ◽  
Vol 24 ◽  
pp. 233121652093616
Author(s):  
Maureen J. Shader ◽  
Sandra Gordon-Salant ◽  
Matthew J. Goupell

Although cochlear implants (CIs) are a viable treatment option for severe hearing loss in adults of any age, older adults may be at a disadvantage compared with younger adults. CIs deliver signals that contain limited spectral information, requiring CI users to attend to the temporal information within the signal to recognize speech. Older adults are susceptible to acquiring auditory temporal processing deficits, presenting a potential age-related limitation for recognizing speech signals delivered by CIs. The goal of this study was to measure auditory temporal processing ability via amplitude-modulation (AM) detection as a function of age in CI users. The contribution of the electrode-to-neural interface, in addition to age, was estimated using electrically evoked compound action potential (ECAP) amplitude growth functions. Within each participant, two electrodes were selected: one with the steepest ECAP slope and one with the shallowest ECAP slope, in order to represent electrodes with varied estimates of the electrode-to-neural interface. Single-electrode AM detection thresholds were measured using direct stimulation at these two electrode locations. Results revealed that AM detection ability significantly declined as a function of chronological age. ECAP slope did not significantly impact AM detection, but ECAP slope decreased (became shallower) with increasing age, suggesting that factors influencing the electrode-to-neural interface change with age. Results demonstrated a significant negative impact of chronological age on auditory temporal processing. The locus of the age-related limitation (peripheral vs. central origin), however, is difficult to evaluate because the peripheral influence (ECAPs) was correlated with the central factor (age).


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S745-S746
Author(s):  
Jamie N Justice ◽  
George A Kuchel ◽  
Nir Barzilai ◽  
Stephen Kritchevsky

Abstract Significant progress in the biology of aging and animal models supports the geroscience hypothesis: by targeting biological aging the onset of age-related diseases can be delayed. Geroscience investigators will test this hypothesis in a multicenter clinical trial, to determine if interventions on biological aging processes can prevent accumulation of multiple age-related diseases and aging phenotypes in older adults. Prodigious activity is underway to develop markers of biological aging, but currently there is no aging biomarker consensus to support geroscience-guided clinical trial outcomes. We convened an expert committee to establish a framework for selection of blood-based biomarkers, emphasizing: feasibility/reliability; aging relevance; ability to predict clinical trial outcomes; and responsiveness to intervention. We applied this framework and identified a short-list of blood-based biomarkers with potential use in multicenter trials on aging. We review progress on efforts to test these candidate biomarkers of aging and development of biomarkers strategy for geroscience-guided clinical trials.


2019 ◽  
Vol 91 (4) ◽  
pp. 501-519 ◽  
Author(s):  
Masahiro Toyama ◽  
Heather R. Fuller

Stress can negatively affect multiple aspects of health, including functional health, among older adults, who are likely to face unique, age-related stressful experiences. Previous research has addressed the protective effects of social relations (i.e., social ties, social participation, and social integration) for physical and mental health outcomes, yet few studies have examined functional health. This study aimed to investigate the longitudinal stress-buffering effects of social integration on late-life functional health. Using three-wave data from 399 older adults (aged older than 60 years), two-level hierarchical linear modeling analysis was conducted and the results indicated that in addition to its main effect on functional (activity of daily living) limitations, social integration moderated the negative effect of stress on the longitudinal trajectory of functional limitations. The findings suggest important directions of future research to identify the mechanisms of such buffering effects over time and develop effective interventions to enhance late-life functional health while promoting social integration.


2020 ◽  
Vol 6 (3) ◽  
Author(s):  
Alebtekin Ahangari ◽  
Mohammad Abdolrahmani

Kinesiophobia is one of the pain complications which eventually might cause disability. Several studies showed correlation between age-related problems with kinsiophobia. The objective was to investigate clinical trials about managing kinesiophobia among older adults aged +65 years until March 2020. PubMed, CINAHL, Google Scholar, and PsycINFO databases were electronically searched until March 2020. All studies about kinesiophobia, with clinical trials, and randomized trials study design among older adults aged +65 years were included in the review. Two set of searching terms including ‘kinesiophobia AND intervention’ and ‘fear of movement AND intervention’ were used. From a total of 2669 articles, after excluding for different reasons, only three articles with total of 87 participants, mean age 68.5, all from Turkey related to the objectives of this study remained. Two of them were evaluated using two different physiotherapy approaches to manage neck pain and low back pain and one of them was regarding falls. Kinesiophobia was used as measure for the effectiveness of treatments. Older adults with routine and properly designed exercise and activity are healthier, with a lower probability for disability and therefore higher quality of life and longer healthy life. But to reach those goals, agerelated diseases and barriers should be investigated.


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