Tuesday, January 19, 2016

Uncertain Health in an Insecure World – 72

“White Drops of Immortality”

Many myths and religious beliefs relate to longevity. Powerful rulers, kings and pharaohs, have been obsessed with longer life and the afterlife. In East Asian mythology, the ‘elixir of life’ is brewed by a white hare on the Moon (below) – a potion that when consumed in a special cup at certain hour imbues eternal life. Alchemists in various ages and cultures have long sought such “white drops of immortality”.

But we are mere mortals, not gods or demi-gods.

And with the losses last week of David Bowie and Alan Rickman at age 69 from liver and pancreatic cancer, and yesterday of Glenn Frey at 67 from ulcerative colitis complications, we are rudely reminded of our own mortality. Global human life expectancy at birth (LEB) is currently 71 years (see post #71). David, Alan and Glenn almost made it…

The longest lived human on record, Jeanne Calment, died at an age of 122 years. In the Bible, Moses led the Exodus from Egypt at age 80, and is said to have lived 120 years.

Today, 63 years since James Watson and Francis Crick decoded DNA’s double helix, nearly 20 years since the Human Genome Project, we humans are no closer to living longer as a species.

Understanding something does not guarantee results.

Epidemiological data implicates two kinds of genetic influences on human longevity: 1) parental consanguinity (first cousins intermarrying; see map below) producing homozygous allele recessive gene expression, increasing the incidence of multifactorial traits, and 2) advanced paternal age at conception, leading to new mutations in the population.

The heritability of genes that promote longevity and healthy aging is immensely complex, and each human aging phenotype is uniquely influenced by its surrounding environment. Genome wide association studies (GWAS) have identified several interesting gene-trait longevity relationships, but none have achieved genome-wide scientific significance. In a Leiden Germany GWAS, the APO E4 gene (see post 71) has been shown to be deleterious to longevity.

The sixty-two wealthiest humans have more wealth than the poorest 3.5 billion. Many of these modern ultra-wealthy are enamored of longevity. In their remaining years, many will spend much of their personal fortunes in a scientific search for the elixir of life.

Silicon Valley has A LOT of enthusiasm for tapping into technology to restore the fountain of youth. For example, hedge funder Joon Yun (age 49) has established the Palo Alto Longevity Prize – a $1M life sciences competition dedicated to ending aging. Half of the prize money will go to scientists who can stop and then reverse human physiology in order to restore homeostasis of heart rate variability to that of a young adult. To receive the other half of ‘The Prize’, scientists will need to demonstrate an invention that extends mammalian life by 50% beyond the average for that species.

Can the code of life be hacked? Billionaires and their companies are bullish about reverse-engineering biology to extend life. 

Google’s CEO Sergei Brin (age 41) founded Calico in 2013. Calico, short for California Life Company, is a biotech with the mission of devising “interventions that enable people to lead longer and healthier lives.” With a seemingly endless bankroll of funds, Calico scientists like Cynthia Kenyon have genetically engineered roundworms that live 6-times longer than normal. Calico and pharma giant AbbVie joined forces in 2014 to pour $1.5B into anti-aging research. By comparison, the NIH’s National Institute on Aging (NIA) annually allocates $1.17B into this science of aging domain, including a special $100M budget boost for Alzheimer’s research. Brin has a gene that predisposes Parkinson’s disease, and his wife co-founded 23andMe.

Bio-technologist pioneer Craig Venter (age 68) and successful tech entrepreneur and ‘X Prize’ founder Peter Diamandis (age 54) have formed a newco called Human Longevity Inc (HLI), to develop a giant database of 1 million human genome sequences by 2020. HLI includes big data from super-centenarians who live beyond 110 years (only 1 in 1,000 of those living to 100 years). Venter envisages that HLI and Calico will join forces so, together, “it can help me live longer.”

To most humans, aging seems unavoidable.

Google’s Aubrey de Grey (age 52) is not one of them. A long-bearded maverick who serves on the Palo Alto Longevity Prize board, de Grey claims that the world is in a “pro-aging trance” that accepts the inevitability of aging as a being a medical problem. His avant-garde beliefs, such as the first person who will live to 1,000 years having already been born, make him unpopular with some mainstream anti-aging scientists. After all, the Bible states that Noah lived to 950, although God forbade life beyond 120 years after The Flood.

Aging is physiology, not illness. People without serious diseases do simply die of “old age.”

Since 2009, de Grey has been the CSO at the Strategies for Engineered Negligible Senescence (SENS) foundation, to which Silicon Valley PayPal billionaire and VC heavyweight Peter Thiel (age 47) has generously contributed. Yearly, SENS carries out $5M of anti-aging research. Several other billionaires have foundations designed to extend the human ‘health span’ – life before the frailty of aging sets in. The (Larry, age 70) Ellison Medical Foundation and the Paul (age 71) Glenn Foundation for Medical Research are two examples, where research on resilience against later lifespan extension is still occurring, despite LEB gains due to successes in childhood disease treatments and global public health. 

The genes of mice are not of men.

Despite scientific successes extending the lives of round worms and mice, the human aging condition seems resistant to change. There are now >20 mouse models of drug-induced longevity! The scientific community, skeptical a decade ago about drugs and diets extending life, has grown enthusiastic about interventions that reduce cancer risk from immune system burnout, and the deadly march of neuro-degeneration. Novartis has drugs that improve the immune response to flu vaccine by 20%. Glaxo-Smith-Kline has purchased the rights to plant-derived resveratrol that extends yeast cell and mouse lifespans, and stabilizes amyloid plaques in Alzheimer’s Disease. Stanford scientists are studying whether blood transfusion from young donors extend the lives of older recipients.

Public health policy longevity initiatives are slowly emerging.

The EU Healthy Ageing Initiative has recently established an official policy goal of extending health span by two years by 2020 as a shared societal goal! Average EU LEB for males is currently 76 years, and 82 years for females. The massive infusion of Syrian refugees make this all seem aspirational (see post #69).

The UK Human Longevity Panel has robustly debated whether evidence supports efforts to stretch human lifespans beyond 120 years, with some experts “believing that there was no limit.” Published biology supports the 12 decade hard ceiling, but enthusiasts like Craig Venter say, “I don’t see any absolute biological limit on human age.”

Like the pharaohs, modern billionaires can invest their riches in what they choose.

Scientists are honorably compelled to study prolonging the human condition.

The songs and portrayals of rockers and actors outlive their creators.

We in the Square are moved to wonderment by these modern mythologies.

And for us all, “It ain’t over ‘til the fat lady sings.” 

Until it is… 

1 comment:

  1. Great and thought provoking article. Just hope somebody is doing the math regarding supporting the future population.