Showing posts with label biomarkers. Show all posts
Showing posts with label biomarkers. Show all posts

Sunday, May 16, 2010

Unified health data climate

The future of health management and biosecurity is having always-on access to the health data climate of individuals, families, communities, and countries. A whole new era of health awareness and self-management could be possible. Ideally, health data streams would be automatically captured and parsed into a comprehensive tableau of status monitoring and action-taking.

Key health data streams (Figure 1):

  1. Genome - whole human genome sequence, abnormal tissue sequences (cancer, etc.)
  2. Phenotype - current status of a wide range of biophysical markers including blood-based organ-secreted proteins prognosticating disease, cholesterol levels, blood pressure, and emotional state
  3. Diseasome - catalog of cumulative immune system exposures and predicted response to toxins
  4. Microbiome - microflora bacteria profile (gut, genital, skin, oral, etc.)
  5. Environmentome - external environment measures including air and water quality, pollen/allergens count

Figure 1: Key health data streams.

Sunday, June 21, 2009

Health Literacy Toolkit

With one key life sciences focus shifting to health as opposed to healthcare (as HealthCamp founder Mark Scrimshire exhorts) and to preventive, predictive health management as opposed to therapy and treatment, there should be the concept of a health literacy toolkit that would be a component of standardized knowledge, such as how to write, drive or get a job.

Definition of health literacy
Surprising but emblematic of the traditional health mentality (e.g.; treat illness) is the prevailing definition of health literacy…”a patient’s ability to acquire and understand information about a condition and options once diagnosed…” Moving into the preventive era, the definition of health literacy needs to shift from being backward-looking to forward-looking. Having health knowledge ahead of time could inform behaviors to prevent, slow or lessen the development of disease. Health literacy should be a general set of knowledge for everyone to know, not related to a condition once a patient has it.

Gap between health literacy and demand for health information
A U.S. Department of Health and Human Services (HHS) study finds that only 12% of adults have proficient health literacy (p. 26); that nearly 9 out of 10 adults may lack the skills needed to manage their health and prevent disease.

The biggest reason for low health literacy could be a lack of appropriately accessible and presented health information.
A Pew Internet Study “The Social Life of Health Information” in June 2009 finds that 61% of U.S. adults are looking for health information online. The gap between health literacy and the demand for health information suggests that there is a substantial opportunity for a range of health information services and management tools, many of which could be fee-based such as the LIVESTRONG nutrition and exercise management program.

Health literacy toolkit
What should be the components of a standard health literacy toolkit? Many professionals (e.g.; physicians, academicians, etc.) believe that even HDL/LDL cholesterol information is too complicated for the lay public, but this just cannot be correct. When simple numeric information is presented clearly, people of any background and capability are often quite able to understand it and take action. For example, when utility bills started to provide straightforward quantitative data regarding power consumption, including day/night usage and costs, many people shifted their behavior in a positive informed way.

Figure 1: Ongoing Total Cholesterol readings for one individual


Figure 1 illustrates an example individual’s ongoing total cholesterol readings presented in a clear and informative way. Anyone inspecting the chart can easily identify the overall trend, down, which is good, wonder about the range of numeric measurements (157-185) vs. the average and how this translates into good or bad health tiers (e.g.; under 200 is generally good, but a rising trend that is still under 200 could be an indication of arising health issues for that individual), and inquisitively wonder about the peaks. The next level of information would be HDL and LDL readings, small lipids as is now de rigueur and triglycerides, but even this simple plot of total cholesterol measures is understandable, useful and potentially actionable. It is also the perfect level of information for individuals who are interested in being responsible for self-managing their health but from an efficient, easily-actionable level that does not require deep engagement of time or knowledge acquistion.

Some of the most obvious aspects to include in a health literacy toolkit would be nutritional information and its interpretation, caloric consumption and expenditure and ongoing quantitative measures of health from blood analysis and other tests (e.g.; blood pressure, glucose, cholesterol, BMI, weight, VO2 max, etc.). The data can be summarized (with detail available) and directly linked to actionable explanatory information (e.g.; measures may go up or down if they were not measured at the same time or situation, for example if a meal had been eaten before some but not all of the measurements). Other components of a standard health literacy toolkit could include where and how to obtain information and tools for self-tracking, how to integrate multiple data sources into a unified view, and how and what to expect when interacting with the medical community. Genomics is already part of the health literacy toolkit for early adopters and could become a standard toolkit component for everyone within five years, already helpful Genetics 101 sites are emerging.

Automated health monitoring tools
Health-self management in large quadrants of the population could accelerate with the advent of automated health monitoring tools that would capture frequent datapoints and aggregate the information into easily viewable web-based charts. Many devices such as blood pressure monitors, heart monitors and scales are now battery-intensive Bluetooth-enabled which is a nice intermediate step but what is really needed is for all of these monitoring devices to be directly on home WiFi networks. Where possible, having the monitoring applications directly on the smartphone is another obvious step rather than having separate devices. There are some WiFi-enabled devices, for example the FitBit calorimeter, which has been delayed in launching, and glucose monitors such as the GlucoMON, however its $75/month subscription fee appears exorbitant.

Sunday, June 07, 2009

Aging is solvable

That aging is understandable and solvable, not necessarily immediately but ultimately, was one topic not seeing a lot of opposition at the American Aging Association (AGE) conference in Phoenix AZ May 29 – June 1, 2009. Key research highlights are below.

Aging is a key contemporary concern, on the order of climate change, as all countries worldwide have populations increasingly stratified towards aging. Aging is not just a medical condition but a key challenge to be resolved for advanced societies to be successful in the long-term. Productivity, healthcare costs and happiness and comfort could all be improved with advances in the remedy of aging. Aging has advanced from a nebulous concept to concrete mechanisms that can be understood and managed. Thematically, most of the bioparts impacted in aging (cells, genes, proteins, neurons, etc.) seem to still be present in older organisms, just not functioning the way they did when the organisms were younger, suggesting that it may be possible to manage and reverse aging processes, and confirming the systemic nature of aging including, for example, the role of a healthy microenvironment and cell-cell signaling. Reductionism as an approach has proved unsuccessful.

Aging is a multidisciplinary phenomenon, involving different deterioration processes in different tissues over time. Aging involves a variety of fields (immunology, cancer, regenerative medicine, cognition, micronutrients, etc.) and a variety of levels of research species (C. elegans (worms), Drosophila (flies), mice, rats and humans). At AGE, the organizational structure was a focus on systems pathways, particularly signaling and hormones, together with a look at the role of proteins in aging.

AGE was an excellent place to obtain a broad and deep comprehension of how aging works. The systemic rigor required to characterize the process-intensive nature of aging has been making significant progress, with a much more detailed understanding of the complex nested multifactor pathways now existing as compared with that of even a few years ago. It is clear that the painstaking characterization work could be further improved with automation and quantitative tools, especially for example, digital linkage of aging pathways across organisms.

As with other life sciences areas, the potential widespread quick and cheap availability of the sequencing of genomes, proteomes, etc. is likely to dramatically change how the science of aging is conducted, though not guarantee quick solutions. As pathways continue to be confirmed, they can be digitized into software and nearly indefinite simulated iterations could be run before conducting time-consuming and expensive bench experiments in confirmation.

Many interventions work for extending the lifespans and healthspans of lower order organisms, for example knocking out any one of 200 known genes may extend the lifespan of the C. elegans worm but the specifics and replicability of the mechanisms in higher order organisms are not known. It does not make sense to directly translate point solutions up to mammals given the systemic nature of the organisms and aging processes. Even moving one biomarker for alcohol consumption from monkeys to humans is not direct.

Exciting new research findings
Reference links below and conference abstracts here

  1. 3-D organ printing: Use only biologics (cells and cell products) in a scaffold-free tissue engineering process to print 3-D tissues and organs which can be vascularized prior to implantation, relying on developmental biology to trigger the cells to fuse and self-assemble into organs. (Gabor Forgacs, video, lab, organ printing)
  2. Stem cell antibodies: Improve existing cardiac stem cell therapies (only 1% of cells reach the intended destination) by using specific antibodies for better targeting and retention of stem cells at sites of tissue injury. Replace cardiomyocytes with adult stem cells. (Jim Larrick, paper, general information)
  3. Stem cells: Amplify and rejuvenate adult stem cells for injection into knees and hips as an alternative to surgical replacements. (Regenexx)
  4. Bioremediation: Use natural enzymes to remediate biological build-ups; cholesterol oxidase from Brevibacteria to reduce 7KC cholesterol in atherosclerosis and A2E-degrading enzymes to improve macular degeneration. (John Schloendorn, research program, paper)
  5. Life extension: Examine the mechanisms of dietary restriction (DR) with further elucidation of TOR (target of rapamycin) pathways, a fast growing area of research. Find that inhibiting a downstream gene in the TOR pathway, HIF-1 (a transcription factor important for growth and metabolism), extends lifespan in worms. (Pankaj Kapahi, paper)
  6. Life extension: Generate a 10x lifespan extension in C. elegans by silencing many components of insulin/IGF-1 signaling (IIS) possibly via the disruption of PIP3 (a key signaling molecule required for the membrane tethering of many signaling molecules). (Puneet Bharill, paper)
  7. Amyloid plaque reduction: Use a known plaque imaging agent, ThT (Thioflavin T), as a therapeutic for amyloid plaques. (Silvestre Alavez, lab affiliation, paper)
  8. Cancer protection: Find that naked mole rats have two layers of anti-cancer protection, humans have only one. p16 is the first-line-of-defense anti-cancer protection mechanism found in naked mole rats. Humans (and other organisms) also have p16 (a suite of three genes), perhaps the mechanism for its upregulation (probably a cell:cell signaling dynamic) in naked mole rats could be understood and turned on with an enzyme in humans. (Andrei Seluanov, earlier research)
  9. Cognitive function: Find that neurogenesis is possible in aged organisms with exercise followed by cognitive stimulation (e.g.; tackling a puzzle or challenge); organisms can benefit by building up a larger reservoir of brain cells earlier in life by being exposed to a variety of external stimulation. (Gerd Kempermann) This author’s speculation: Perhaps neurogenesis could be further harnessed for brain enhancement beyond currently realizable human capacities as this mechanism is better understood.
  10. Aging biomarkers: Upstream the aging focus to prevention by measuring biomarkers and introducing interventions. Some suggested biomarkers of aging are p16 gene levels (which can be decreased with exercise), telomere length, the level of senescent cells, and the number of circulating lymphocytes in the immune system (measure total T cells (CD3+), B cells (CD19+) and CD28 absolute numbers on CD8+ T cells). (Kronos research projects, test menu; telomere length measuring)
  11. Hormones-IGF: Find no conclusive evidence of insulin-like growth factor's (IGF) ability to retard natural aging, though on an individual basis some people may find it useful. (Marc Blackman)
  12. Hormones-HRT: Find that hormone replacement therapy (HRT) can be good for improving cognitive function and bone loss in women that do not have a risk of heart disease; HRT should be started with the onset of menopause, not later. (Barbara Sherwin, Eef Hogervorst)
  13. Cost of reproduction: Find that ovary removal in grasshoppers resulted in a 25% increased lifespan, contributing to existing evidence regarding the high cost of reproduction. (John Hatle) This author’s speculation: In the farther future, in humans, it could be quite desirable to closely manage fertility, turning it on and off at will, if fertility is even necessary.
  14. Micronutrients: Find tremendous nutritional benefits from the consumption of fruits with skin, especially blueberries (pterostilbene that reduces oxidative stress), blackberries, raspberries, red grapes, pomegranates, cranberries, plums, strawberries, cherries, pears and apples (phytochemicals that provide cancer prevention), walnuts (preventing the inflammation and oxidative stress of brain aging:), green tea (catechins that reduce cardivascular and cancer risk) and tempeh (fermented whole soy bean with folate is healthier than tofu (processed soy bean curd)). (Blueberries: Agnes Rimando, Rolf Martin; Apples: Rui Hai Liu, Walnuts: James A. Joseph, Green tea: Vojo Deretic, Tempeh: Eef Hogervorst)
  15. Calorie restriction (CR)/dietary restriction (DR): Find that in humans, improved biomarkers for CR/DR, vegan and raw food diets that result in the extension of the onset of aging challenges. (John Holloszy)
  16. Aging mice testbed: A mouse type that sufficiently recapitulates early aging, the human WS phenotype (Werner syndrome), has been created which could hasten mammalian aging research. (David Kipling)
Conclusion
Aging is a key contemporary issue. Research is advancing both incrementally and radically in every area of aging. The highest immediate impact could come from working on aging problems upstream at important fulcrum points that impact everything below them, such as genetics, epigenetics and the immune function. The research is progressing and it is starting to be time for VCs, big pharma and DIYbio’ers to take advantage of the many interesting and actionable possibilities.