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From the Townsend Letter
January 2016

Anti-Aging Medicine
Advancements in Anti-Aging Diagnostics
by Ronald Klatz, MD, DO, and Robert Goldman, MD, PhD, DO, FAASP
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To achieve the triple-digit lifespan, science will harness the Biotech Singularity, whereby we leverage cutting-edge technologies to bridge the gap between the medical knowledge of today and the medical knowledge that we will have in our grasp by the year 2029. As a result, it is not impracticable nor improbable to expect that humankind will reach the point where we'll know how to substantially slow or perhaps even stop aging, and even eventually reset the clock mechanism of life itself.
A key element for achieving the Biotech Singularity is diagnostic medical technologies, which will enable earlier and accurate assessment of diseases. This column shares some of the latest and promising advancements in anti-aging diagnostics that may enable this goal.

Saliva Suggests Cognitive Changes
Cortisol is a hormone that when produced at high levels (often in response to emotional stress) can have a toxic effect on the hippocampus area of the brain – a region with an important role in memory. Lenore J. Launer and colleagues from the National Institute on Aging (Maryland, US) assessed 4244 people, average age of 76 years and without dementia, enrolled in the Agee, Gene/Environment Susceptibility (AGES)-Reykjavik Study. Subjects were assessed via MRI for brain volume, and their saliva was collected at home 45 minutes after awakening and at night. Higher evening cortisol associated with smaller total brain volume, with the smaller volumes observed in all brain regions, but significantly smaller in gray matter than in white matter regions. Further, higher evening cortisol associated with poorer cognitive functioning. In contrast, higher levels of morning cortisol associated with slightly greater normal white matter volume and better processing speed and executive functioning. The study authors submit: "In older persons, evening and morning cortisol levels may be differentially associated with tissue volume in gray and white matter structures and cognitive function."

Geerlings MI, Sigurdsson S, Eiriksdottir G, et al. Salivary cortisol, brain volumes, and cognition in community-dwelling elderly without dementia. Neurology. 2015 Aug 19. pii:10.1212/WNL.0000000000001931.

Protein Patterns May Signal Alzheimer's
Changes in the spinal fluid during middle age may identify people at risk of developing Alzheimer's disease later in life. Anne Fagan and colleagues from the Washington University School of Medicine (Missouri, US) studied a group of 169 cognitively normal men and women, ages 45 to 75 years when they entered the study – and followed them for 10 years. Each subject received a complete clinical, cognitive imaging, and cerebrospinal fluid biomarker analysis every 3 years, with a minimum of two evaluations. At the participants' initial assessments, researchers divided them into three age groups: early middle age (45–54); mid-middle age (55–64), and late middle age (65–74). The researchers tracked changes in amyloid beta 42, a protein that is the principal ingredient of Alzheimer's plaques; tau, a structural component of brain cells that increases in the cerebrospinal fluid as Alzheimer's disease damages brain cells; YKL-40, a newly recognized protein that is indicative of inflammation and is produced by brain cells; and the presence of amyloid plaques in the brain, as seen via amyloid PET scans. Observing drops in amyloid beta 42 levels in the cerebrospinal fluid, then the appearance of plaques in brain scans years later among cognitively normal participants ages 45 to 54, the researchers say that the data suggest that patterns of amyloid levels in cerebrospinal fluid in midlife may presage Alzheimer's disease in later years. They also found that tau and other biomarkers of brain-cell injury increase sharply in some individuals as they reach their mid-50s to mid-70s, and YKL-40 rises throughout the age groups focused on in the study. Writing, "Longitudinal [cerebrospinal fluid] biomarker patterns consistent with [Alzheimer's disease] are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline," the study authors submit: "Such measures may be useful for targeting middle-aged, asymptomatic individuals for therapeutic trials designed to prevent cognitive decline."

Sutphen CL, Jasielec MS, Shah AR, et al. Longitudinal cerebrospinal fluid biomarker changes in preclinical Alzheimer disease during middle age. JAMA Neurol. 2015 Jul 6.

Listen for Cancer
In that existing methods of separation use tumor-specific antibodies to bind with the cancer cells and isolate them – requiring that the appropriate antibodies be known in advance – and other methods rely on specific molecular properties, Peng Li and colleagues from the Pennsylvania State University (US) have innovated a novel acoustic tweezers device about twice the size of a penny, with two sound transducers that separate cells by detecting the differential sizes and weights to push the circulating cancer cells out of the fluid stream and into a separate channel for collection. The power, intensity, and frequency used in this study are similar to those used in ultrasonic imaging, and each cell experiences the acoustic wave for only a fraction of a second. The researchers used two types of human cancer cells to optimize the acoustic separation – HELA cells and MCF7 cells, which are similar in size. Their separation experiment yielded a separation rate of more than 83%. Writing, "We report the development of an acoustic-based device that successfully demonstrates the isolation of rare [circulating tumor cells] from the clinical blood samples of cancer patients. Our work thus provides a unique means to obtain viable and undamaged [circulating tumor cells]," the study authors submit: "The results presented here offer unique pathways for better cancer diagnosis, prognosis, therapy monitoring, and metastasis research."

Li P, Mao Z, Peng Z, et al. Acoustic separation of circulating tumor cells. PNAS. 2015;112(16):4970–4975.

Telomeres Tell of Cancer
Telomeres are the end caps of chromosomes, protecting the DNA complexes from deterioration during cell division. Telomere shortening is considered a marker of cellular aging, and prematurely shortened telomeres have been linked to increased risk of cancers, heart disease, dementia, and death. Lifang Hou and colleagues from Northwestern University (Illinois, US) took multiple measurements of telomeres over a 13-year period in 792 persons, 135 of whom were eventually diagnosed with different types of cancer, including prostate, skin, lung, leukemia, and others. The team found that initially telomeres aged much faster (indicated by a more rapid loss of length) in individuals who were developing but not yet diagnosed with cancer: telomeres in persons developing cancer looked as much as 15 years chronologically older than those of people who were not developing the disease. Then the researchers observed that the accelerated aging process stopped 3 to 4 years before the cancer diagnosis. The lead investigator comments: "This pattern of telomere growth may mean it can be a predictive biomarker for cancer."

Gu J. Leukocyte telomere length and cancer risk: a dynamic problem. EbioMedicine. May 20, 2015.

Holograms for Health
Responsive holograms that change color in the presence of certain compounds are being developed into portable medical tests and devices, which could be used to monitor conditions such as diabetes, cardiac function, infections, and electrolyte or hormone imbalance easily and inexpensively to test blood, breath, urine, saliva, or tear fluid for a wide range of compounds, such as glucose, alcohol, hormones, drugs, or bacteria. When one of these compounds is present, the hologram changes color, potentially making the monitoring of various conditions as simple as checking the color of the hologram against a color gradient. Researchers from the University of Cambridge (UK) use a highly absorbent material known as a hydrogel, similar to contact lenses, impregnated with tiny particles of silver. Using a single laser pulse, the silver nanoparticles are formed into three-dimensional holograms of predetermined shapes in a fraction of a second. When in the presence of certain compounds, the hydrogels either shrink or swell, causing the color of the hologram to change to any other color in the entire visible spectrum, the first time that this has been achieved in any hydrogel-based sensor. A major advantage of the technology is that the holograms can be constructed in a fraction of a second, making the technology highly suitable for mass production. While these sorts of inexpensive, portable tests aren't meant to replace a doctor, holograms could enable people to easily monitor their own health.

Yetisen AK, Butt H, da Cruz Vasconcellos F, et al. Light-directed writing of chemically tunable narrow-band holographic sensors. Adv Opt Mater. 2 Jan. 2014.

Disease Detection by Smartphone
Indeed, technology is a cornerstone in the evolution of medical diagnostics. Researchers around the world are developing smartphone applications to enable fast, inexpensive, accessible, noninvasive detection for a wide range of diseases. A consortium led by Hossam Haick from the Technion-Israel Institute of Technology (Israel) is developing a product that, when coupled with a smartphone, will be able to screen the user's breath for early detection of life-threatening diseases. The SNIFFPHONE project links breathalyzer screening technology to the smartphone, utilizing micro- and nanosensors to read exhaled breath and transfer the information through the attached mobile phone to an information-processing system for interpretation. The data are then assessed, and disease diagnosis and other details are ascertained.  Separately, Samuel K. Sia and colleagues from Columbia University (New York, US) have devised a low-cost smartphone accessory that can perform a point-of-care test that simultaneously detects three infectious disease markers from a finger prick of blood in just 15 minutes. The device replicates, for the first time, all mechanical, optical, and electronic functions of a lab-based blood test. Specifically, it performs an enzyme-linked immunosorbent assay (ELISA) without requiring any stored energy: all necessary power is drawn from the smartphone. It performs a triplexed immunoassay not currently available in a single test format: HIV antibody, treponemal-specific antibody for syphilis, and nontreponemal antibody for active syphilis infection. The study authors submit: "The overall system aims to be portable, robust, low-power, and fully utilize the ability of mobile devices for bringing better health care to resource poor areas."  

Sia et al.: Guo TW, Laksanasopin T, Sridhara AA, Nayak S, Sia SK. Mobile device for disease diagnosis and data tracking in resource-limited settings. Methods Mol Biol. 2015;1256:3–14.

To stay updated on the latest advancements in anti-aging diagnostic medical technologies, visit the World Health Network (, the official educational website of the A4M and your one-stop resource for authoritative anti-aging information. Be sure to sign up for the free Longevity Magazine e-journal, your weekly health newsletter featuring wellness, prevention, and biotech advancements in longevity.

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