Goal 1: Promote Human Health

Understanding normal aging

Understanding normal aging

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

While we are fully supportive of the recent emphasis on patient‐centered outcomes and implementation science, we are also reminded of the critical importance of investigating underlying mechanisms of pulmonary, critical care and sleep disorders. Recent discoveries have created exciting progress in the areas of cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and biological therapies in asthma. Only through further efforts to elucidate underlying mechanisms are new therapeutic approaches likely to emerge. Promoting further academic‐industry interactions are likely to yield benefits, which will ultimately lead to improvements in the health of our nation.

Name of idea submitter and other team members who worked on this idea : Research Advocacy Committee, American Thoracic Society

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Goal 2: Reduce Human Disease

Can we promote healthy aging / increase longevity?

Can we identify (and target) more precise mechanisms underlying age-related diseases such as idiopathic pulmonary fibrosis?

Submitted by (@sunad0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

With increasing median survival around the world, there is an increasing need to address non-infectious disease processes that affect the aging body.

 

Caloric restriction is among the few interventions that can promote healthy aging and prolong life. Some of the putative pathways described so far include AMPK, mTOR and Sirtuins. Many pathways seem to have relation to autophagy.

 

Elucidating these mechanisms may potentially enable identifying therapeutic targets that translate to healthy aging, if not prolonging lifespan.

Feasibility and challenges of addressing this CQ or CC :

Prolonging lifespan in yeast, flies, worms or even mice cannot easily be translated to humans. For example, Metformin (AMPK activator) has been shown to prolong lifespan in mice (Nat Commun. 2013;4:2192. doi: 10.1038/ncomms3192). As is known, Metformin is indicated in type 2 diabetes mellitus (DM) and is indeed being taken by millions of patients with type 2 DM worldwide. However, its beneficial effects in patients with type 2 DM are offset by comorbidities such as frailty in older adults (J Endocrinol Diabetes Obes. 2014;2(2). pii: 1031). It remains to be seen what sort of a preclinical study would cross the threshold for metformin to be recommended as a health / longevity supplement for everyone, say, beyond 40 years of age.

 

Other potential candidates include mTOR inhibitors, Sirtuin activators and potentially, autophagy enhancers. Obviously much more research is needed in this direction.

Name of idea submitter and other team members who worked on this idea : Sunad Rangarajan

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Goal 2: Reduce Human Disease

What is the role of chronic inflammation in lung complications in the HAART era?

With the advent of HAART HIV-infected subjects are living longer. Lung infectious complications so common in the early stages of the HIV epidemic have been replaced by those associated with chronic inflammation (COPD, pulmonary hypertension, lung cancer). Furthermore, this chronic inflammation is likely contributing to premature vascular complications (i.e coronary disease) seen in this population. All of these complications ...more »

Submitted by (@htwig0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Addressing the role of chronic inflammation in chronic lung and vascular diseases will impact both the HIV population and our growing U.S. aging population. Approaches to the question could include:

1.. Causes of chronic inflammation

- Antiretroviral drugs, persistent HIV, persistence of other viruses, exogenous retroviral elements, exosomes, other epidemiologic exposures

2. Downstream mechanistic effects of chronic inflammation

- Alterations in gene regulation, alterations in oxidative stress, direct tissue damage

3. Clinical outcomes of chronic inflammation

- Lung – COPD, pulmonary HTN, cancer, interstitial lung disease, asthma.

- Vascular compartment - premature coronary and vascular disease

- Does HIV-infection itself require alterations in treatment modalities for lung disease

- Does HIV infection itself alter the outcome of chronic lung disease?

4. Therapeutic options

- Directed against the cause – i.e. antivirals.

- Immune specific targets against inflammatory mediators

Feasibility and challenges of addressing this CQ or CC :

The critical challenge for this question lies in the fact that complications caused by chronic inflammation such as COPD and coronary disease will by definition take years to develop. Intervention trials will take even longer. This is not like the early HIV epidemic, where complications were primarily infectious and could be seen and addressed quickly. Because of this chronic nature, it will necessary to try and establish cohorts with long term follow-up. Furthermore, it will be critical to have well defined appropriate HIV-uninfected cohorts to compare the HIV-infected population to.

Name of idea submitter and other team members who worked on this idea : Homer L. Twigg III on behalf of the INHALD Consortium

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Goal 2: Reduce Human Disease

What is the Relationship Between CVD and Dementia in the Elderly?

The successes of preventing and treating CHD, CVD has resulted in a substantial increase in life expectancy, a very important success story, but unfortunately it has led to a growing population of elderly 80+ years of age.

Submitted by (@kullerl)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Their high prevalence of congestive heart failure (CHF), atrial fibrillation (Afib), stroke, peripheral vascular disease, dementia, frailty, and disability is clearly going to lead to the public health tsunami of the 21st century and bankrupt the health systems. Further studies are badly needed to determine the interrelationship between CVD, dementia, disability, and whether prevention of CVD beginning early in life, middle ages, or even at older ages can impact on successful aging with reduced risks of dementia and disability.

Feasibility and challenges of addressing this CQ or CC :

Older individuals with 0 coronary artery calcium (CAC) have extremely low risk of subsequent clinical CHD, CVD, and total mortality even at older ages. Whether these individuals with low risk, e.g. very low CAC, have less extensive brain abnormalities associated with increased risk of dementia needs to be evaluated.

 

The NHLBI should establish a registry of individuals who have had very low CAC scores at older ages, determine the relationship between these very low CAC scores and risk factors, genetics, and then consider trials to prevent CVD, CHD among older individuals 80+ with relatively low levels of CAC, with dementia, stroke, CHF, Afib, as primary endpoints. The NHLBI should also consider trials in middle-aged individuals to prevent the development and progression of coronary atherosclerosis, e.g. maintenance of 0 CAC. The NHLBI, in collaboration with other institutes at NIH, should evaluate the interrelationship between coronary artery atherosclerosis, e.g. CAC, and other measures of atherosclerosis, other manifestations of CVD, such as CHF, Afib, and brain changes and the development of dementia and Alzheimer’s disease.

Name of idea submitter and other team members who worked on this idea : Lewis H. Kuller, MD, DrPH

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Goal 1: Promote Human Health

Mechanisms of cardiac aging

The electrical and mechanical function of cardiac myocytes is compromised with age, but little is known about the age-related changes that occur within individual myocytes.

Submitted by (@catherine.proenza)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

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32 up votes
13 down votes
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Goal 3: Advance Translational Research

Research Opportunities in HLB to Facilitate Aging in Place

There is a need for greater evidence-based research over the next 5-10 years to reduce healthcare costs, reduce hospitalizations, and support older persons with significant heart, lung, blood, sleep conditions to remain in their private homes if feasible, if technology is utilized that fosters clinical and epidemiologic research.

Submitted by (@nhlbiforumadministrator1)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

No other force will have as big of an impact on our health system as the unalterable rate of our aging population and subsequent increased rate of heart, lung and blood diseases. The impact of doing nothing is unforeseeable.

Feasibility and challenges of addressing this CQ or CC :

Evidence-based research over the next 5-10 years to reduce healthcare costs, reduce hospitalizations, and support older persons with significant heart, lung and blood conditions remain in their private homes is feasible if technology is utilized that fosters clinical and epidemiologic research.

Many cardiovascular risk factors increase as the population ages including uncontrolled systolic hypertension and atherosclerosis both contributing to the well-being of our society and increasingly high health care costs (Izzo, Levy, & Black, 2012). No other force will have as big of an impact on our health system as the unalterable rate of our aging population and subsequent increased rate of heart, lung and blood diseases. The impact of doing nothing is unforeseeable.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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Goal 2: Reduce Human Disease

Improving Representation of the Elderly in Clinical Research

There is a need to optimize long-term cognitive and functional outcomes in the aging population during and after cardiothorasic surgery, including the development of simple, objective tools to enable risk stratification for vulnerability to neurocognitive deficit. First, cardiothoracic surgical trials and clinical studies should be more "age-representative" and reflect the increasing proportion of the aging population. ...more »

Submitted by (@nhlbiforumadministrator1)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Many answers would result from including the elderly in ongoing and planned clinical research and trials.

Feasibility and challenges of addressing this CQ or CC :

This population is growing rapidly and available to be studied.

Elderly patients as a group face higher acute risks for complications and death following cardiothoracic surgery or coronary interventions, yet may also gain more long-term benefits from surgery due to their more severe disease. The balance between risks and benefits of surgery may be different in the older patient than in their younger counterparts. Major randomized trials that defined the “standard” for the field (e.g., CASS, VA cooperative, RITA, BARI, STICH) often failed to enroll many, if any, patients aged 75 years or older. The Joint NHLBI-AATS Working Group (http://aats.org/CME/2011-AATS-NHLBI-Symposium.cgi) identified several areas of high priority for cardiothoracic surgery research in the elderly.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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Goal 1: Promote Human Health

Can anti-aging strategies also slow down cardiac aging?

Can anti-aging strategies specifically slow down cardiac aging, and if so, to what extent?

Submitted by (@nhlbiforumadministrator1)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

•May offer new measures of preventing (slowing down) cardiovascular diseases

•Clarify confusions in the field regarding whether these anti-aging strategies improve health-span

Feasibility and challenges of addressing this CQ or CC :

These anti-aging strategies have been well developed and their effects on cardiovascular system can be tested easily. Cardiovascular effects of these anti-aging strategies may even have been studied by investigators who developed these strategies during initial screenings, but need to be investigated more meticulously.

It is well recognized that aging is a major risk factor (if not the biggest) of several chronic diseases, including cardiovascular diseases, although the mechanisms are not exactly understood. Several anti-aging strategies, such as calorie restriction, mTOR pathway inhibition, increased antioxidant responses, and autophagy activation, have been developed to prolong life-span in multiple organisms. The question is whether these strategies will also improve the health-span.

 

Challenges: 1) Cardiac aging can be influenced by multiple factors and the effects of these interventions may be different in different demographic population, if they’re moved onto human studies.

2) Regarding the protective effects of antioxidant therapies, clinical trials of general antioxidants (beta carotene, Vitamin E, or Vitamin C) have been conducted and the results were disappointing. However, a new series of antioxidant agents with catalytic function or mitochondria-targeting, have been developed and may be promising. 3) Need to assemble experts in aging biology and cardiovascular research fields .

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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Goal 2: Reduce Human Disease

Understanding Cardiothoracic Surgery in Elderly Populations

There is a vital need for evidence-based clinical evaluation tools to assess operative risk and post-operative recovery in the elderly, including biomarkers of physiologic age and a simple/reliable clinical evaluation scheme to determine frailty as a risk factor for poor surgical outcomes.

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Development of tools to assess operative risk and post-operative recover in the elderly would improve surgical outcomes in this growing patient population.

Feasibility and challenges of addressing this CQ or CC :

This at risk population is growing rapidly.

Older patients represent an important, different, and under-studied subgroup of those undergoing cardiothoracic surgery according to the Joint NHLBI-AATS Working Group (http://aats.org/CME/2011-AATS-NHLBI-Symposium.cgi). Due to the aging of the US population and the increased severity of coronary and valve disease in older individuals, the use of cardiothoracic surgery in older patients in relative terms is growing rapidly. Between 1990 and 2008, the percentage of those aged 80 years or older has gone from 8% to 16% of total for bypass surgery and 14% to 30% of total for valve surgery.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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56 up votes
17 down votes
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