Preventing Aging Through Darwin-Free Science

Will new discoveries in biochemistry lead to longer lives?  There are hopeful signs that aging can be delayed, if not prevented.  Whether or not that happens in our lifetimes (causing new worries for Social Security), scientists are learning amazing things about how cells work that should give us more reason for Thanksgiving.

1. 100-year-old youth:  Get this. Skin cells taken from donors aged 74 to 101 have been returned to newborn youth, using the induced pluripotent stem cell (iPSC) method of reprogramming cells to the pluripotent state.  According to Science Daily, signs of aging were “erased” in these cells.  They “recovered their capacity for self-renewal and their former differentiation potential, and do not preserve any traces of previous aging.”  This means that age is not a barrier to reprogramming.  Elders can imagine a fountain of youth: “This research paves the way for the therapeutic use of iPS, insofar as an ideal source of adult cells is provided, which are tolerated by the immune system and can repair organs or tissues in elderly patients.”
2. Your personal fountain of youth:  If your own skin cells can be rejuvenated fresh as a baby, why not bank them?  In “Personal Stem Cell Banks Could Be Staple of Future Health Care,” Science Daily discussed that very possibility.  Researchers at the University of Texas Health Science Center found that old stem cells can be rejuvenated by placing them in a young microenvironment.  “This raises the possibility that patients’ own stem cells may one day be rescued and banked to treat their age-related diseases.”  The Texans were apparently unaware of the work cited above that shows even centenarians donating cells that can be regenerated like new: “Older stem cells are not as robust as young ones,” this article claimed.  If they are robust, why not store them like gold for a rainy day?
3. Eternal cells:  Ever since telomeres (like caps on the ends of chromosomes) were found to act as a countdown mechanism for cell division, researchers have been eager to know if their lifetimes can be extended.  There is an enzyme, telomerase, that puts new telomeres on chromosomes, but usually just in embryonic cells.  Medical Xpress reported that scientists at the German Cancer Research Center have found an alternate pathway for telomere lengthening.  Research shows that some cancer cells use this alternate mechanism; that is why they keep dividing without limit.  Learning how to prolong telomeres for good cells and arrest them for tumor cells is an important work in progress (see 9/25/2010).
4. Checking checkpoints:  Having checkpoints makes for good quality control in any engineering process.  Remarkably, cells have checkpoints, too.  Science Daily reported on work at the University of Warwick to study the “spindle checkpoint” in cell division that determines “How Daughter Cells Receive the Same Number of Chromosomes.”  When that checkpoint is breached, aggressive cancer can result.  The article quoted a member of the research team who said, “This cell division process is monitored by the body’s surveillance system known as the ‘spindle checkpoint’, and that is only switched off once everything within the cell is set up correctly. Amazingly, all of the elements of this process are conserved from yeast to human cells.”  Much of biomedical research concerns finding ways to repair mutations to processes that were already there to prevent harm.
5. The navigators:  You don’t have to put a pyramid over your head, according to another article on Science Daily; you already have pyramid-shaped neurons in your cerebellum called “place cells” with a natural alternative to psychic powers.  “Each place cell is activated at specific location of the environment and gives dynamic information about self-location relative to the external world,” the article said.  “These neurons thus generate a cognitive map in the hippocampal system through the integration of multi sensory inputs combining external information (such as visual, auditory, olfactory and tactile cues) and inputs generated by self-motion (i.e. optic flow, proprioceptive [sense of limb position] and vestibular [inner-ear] information).”  Scientists at Ruhr University learned this from mice, but it’s probably true of mice and men, and women, too.
6. Internal sunscreen for that young look:  Tanning: we’ve been warned too much is harmful.  But the melanin in skin and eyes that darkens us upon exposure to ultraviolet light helps protect us, too.  Medical Xpress said that while it takes days for UVB light to give that beach bronze look, our skin reacts much quicker to the more dangerous UVA – even within seconds.  In the skin and the eye, with rhodopsin assisting, melanin production is triggered, absorbing UVA before it can lead to oxidative damage, and “converting it to a less harmful energy in the form of heat.”  That’s what artificial sunscreens try to do anyway.  Thankfully, your skin has heat sensors that remind you to get out of the sun.
7. Rotary teamwork:  ATP synthase made the news again in another wonderful way.  The little rotary engines that generate ATP (the cell’s energy currency) work with other components that lubricate them.  Science Daily reported work at Oxford University that learned how fatty acids interact with the engines.  Sure enough, they “act as a ‘lubricant’ for the motor,” the scientists said. Maybe that gives the edge for the grand prize of 100% efficiency (see 10/14/2011).
8. Rotary recycling:  A cousin of ATP synthase is vacuolar ATP synthase (v-ATPase).  It has the same rotary structure but spends ATP to pump protons into vacuoles and lysosomes, creating acidic conditions where cells break down and recycle used parts.  In Science this week (334:6056, 11/04/2011, pp. 678-683, doi:10.1126/science.1207056), Zoncu et al. found an unexpected connection between v-ATPase and a protein complex in lysosomes named mTOR that is a “master growth regulator that is stimulated by amino acids.”  Elaborating on its important role, they said, “This multicomponent protein kinase integrates inputs from growth factors as well as nutrient and energy supplies to control many biosynthetic and catabolic processes.”  The team discovered that the rotary motor v-ATPase is intrinsically involved in an amino-acid signaling process that causes the mTOR complex 1 to translocate to the organelle surface.  “These results identify the v-ATPase as a component of the mTOR pathway and delineate a lysosome-associated machinery for amino acid sensing,” the researchers said, thus recognizing v-ATPase having a more sophisticated role than just a proton pump. Apparently, the accumulation of amino acids in the lumen of the lysosome activates the motors to pump protons.  This, in turn, puts the mTOR complex into action.

These discoveries suggest more amazement ahead.  “The v-ATPase consists of multicomponent V0 and V1 domains and operates through an incompletely understood mechanism in which each cycle of ATP hydrolysis by the V1 sector generates torque that rotates the membrane domain of V0, known as the rotor,” is how the researchers in the last entry above described the machine.  “In turn, this movement enables the transfer of protons into the lysosomal lumen, causing its acidification.”  Later in the paper, they added, “The v-ATPase is large and complex and has many functions that cannot easily be teased apart in live cells.”  It appears many more fascinating discoveries about cellular machines await.

Does anyone really need commentary after this?  These stories, that owed nothing to Darwin, speak for themselves.  His Victorian mystery religion would have been a distraction.  None of these papers even mentioned evolution: the focus was on elegant engineering, quality control, machinery, process management, and hope for a better life through good old empirical research.  Imagine if Aristotle, Descartes or Leeuwenhoek would have seen what we are seeing now.  Rotary engines!  Checkpoints!  Multi-sensory inputs!  Signaling circuits!  If you are not already thankful, you should be.