Thursday, September 8, 2016

Uncertain Health in an Insecure World – 93

“Swan Song”

Ancient mythology holds that swans, largely hissing or silent creatures in life, sing a beautiful song in the moment just before death. Like humans, swans are biologically inclined to mate for life.

Etruscan bronzes and painted ceramics offer pictorial motifs of the passion of Tithonus for Eos, the Titan of the dawn (below). Greek mythology recounts how Eos asked Zeus to grant her Trojan lover immortality. Zeus granted her wish, literally. But Eos forgot one vital thing… to request that eternal youth accompany Tithonus’ immortality. Eventually, with the passage of years, Tithonus withered into a cicada.

Alfred, Lord Tennyson’s eponymous epic poem, Tithonus (1859), described his infernal decay.
“And after many a summer dies the swan,
Me only cruel immortality, consumes;
I wither slowly in thine arms,
Here, at the quiet limit of the world…”

Since Tennyson’s day, human longevity has crept towards the current 120 year ceiling.

In most organisms, aging processes are inversely proportional to lifespan. “Aging is the gradual loss of molecular fidelity after reaching sexual maturity, culminating in the loss of function (“senescence”) and ultimately in disease and death” (Sen et al, Cell, 2016). In yeast, a maximum number of mitotic cell divisions are followed by a chronological lifespan – the time a cell can survive in a post-mitotic state.

Epigenetics - aging science - explores the cell-based limitations to longevity.

The complex relationship between nuclear chromatin that wraps around histone proteins to form DNA, and enzymes called epigenetic factors, allows (or deflects) access to DNA by transcriptional mRNA copying machinery. At a cellular level, aging is greatly influenced by environmental stimuli and nutrient availability, which contribute to the loss of histones, remodeling of chromatin, and changes in DNA methylation.

Epigeneticists propose that these aging contributors are modifiable, and as such, potentially reversible.

Age is the most powerful contributing risk factor to chronic illnesses like cancer, cardiovascular disease and neuro-degenerative conditions. The central basis of aging (and many diseases) is related to inborn genetic differences and subsequent somatic mutations. This biological maxim is inexorably true of simple single-cell organisms, and of complex beings like humans. 

Jumpy bugs are a new model for epigenetic aging studies.

Social insects like the Indian jumping ant (Harpegnathos saltator, above) provide interesting insights into the epigenetic mechanisms of aging. Remarkably, a worker ant can replace the queen in the colony, and acquire greater longevity, renewed reproductive functions, and the loss of worker behaviors. Of interest, these changes can be reversed! The H. saltator Genome Project has sequenced this ant’s genes. There is up-regulation of certain aging-related genes in the longer-lived reproductive H. saltator ants, and in the expression of SYMD histone methyl-transferase enzymes in select castes within the colony (Bonasio et al, Science 2010).

Long-lived deep-water species may hold the key to understanding the biology of aging.

Arctic water Greenland sharks (Somniosus microcephalus, above) are slow growing, slowly metabolizing creatures that can live for more than 500 years (Nielson et al, Science 2016). With no natural enemies, this species sets the vertebrate longevity bar. These sharks have high concentrations of nitrogenous waste products (urea) and trimethylamine-N-oxide (TMAO) in their tissues, which serve to protect their cells’ osmosis and to increase their water buoyancy. While urea renders their tissues poisonous to predators, TMAO’s counteract the protein-destabilizing effects of urea. Inuit people believe that this behemoth’s bitter flesh acts as a spirit helping to empower their shamans.

The business of staying young has always boomed. Now serious aging science is adding to the mix.

But is science lending real (or false?) hope, and creating endless (or self-perpetuating?) complexity?

Better nutrition and anti-senescence drugs may retard DNA damage and cell dysfunction. Exercise and medical devices can transiently restore physical prowess. Organ transplantation (begun in 1954) could be extended by CRISPR gene & enzyme editing, and expanded by xeno-grafting & 3-D printing to grow new organs. But as noted in The Economist (August 13, 2016), the enormous cost of these “death cheating” interventions creates societal pressures and causes healthcare access inequities.

Average lifespan around the world is primarily a reflection of ‘macro-epigenetics’.

Global population health is mostly related to exposure to air-borne pollutants (above) and environmental toxins, and to the availability of nutritious food and clean water. The Guardian (September 3, 2016) reports that the U.K. charity Children with Cancer has seen a +40% jump in the diagnosis of cancer among teenagers & young adults aged 15 to 24 since 1998. The sanitized version of the cause of this shocking rise is “modern lifestyle”. But obesity, pesticide & solvent inhalation, power lines & magnetic fields, mobile phone radiation, and airborne pollutants are not really novel lifestyles.

Aldous Huxley’s novel, After Many a Summer Dies the Swan (1939), tells the story of a Hollywood magnate who employs a scientist to help him achieve immortality. The Silicon Valley (2016) is full of billionaires investing millions in the science of longevity.

The X-Files scripted sci-fi series season 6 episode Tithonus (1999), recounted the strange story of Alfred Fellig, an immortal photographer. Fellig snapped photos of people on the verge of death (above), appearing to him in shades of gray, in hopes of finally meeting his maker and ending his own cursed long life. For the rest of us, the enormous challenges presented by long life – societal, medical, scientific and ethical – are less metaphysical than physical.

Society is growing confused as to what to do for, and with, the very elderly.

 Science might slow human senescence, but aging per se remains unstoppable.

Tennyson spoke to the futility of fighting the passage of time… “The Gods themselves cannot recall their gifts.”

Eos left Tithonus when his hair turned gray. Lonely, Tithonus wandered her castle until the moment of his human death. As a cryptic cicada, he sang loudly, but only at night, to avoid predators.

If neither the Gods nor man see the long-term benefit of longevity, why then, does the multi-millennial multi-billion dollar quest for longer life continue?

We in the Square who have just passed life’s mid-point remain, in equal parts, puzzled and expectant.

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