The pace and pattern of being

Maturation in mammals varies widely, but the exact reasons why are still unclear. A new method of monitoring growth through observation of teeth and bones may provide the answer.

Why do rats mature faster than humans? While the daily circadian clock controls much of an organism’s daily pace of development, it’s impossible to explain enormous variations in age at maturity and other developmental milestones just by looking at differences in this daily rhythm. Now, metabolomic analysis of blood plasma has for the first time linked these variations to another biological timing mechanism operating on multi-day rhythms of growth and degradation, according to a study published in the online journal PLOS ONE¹.

A rat that grows teeth and bone in a fraction of the time of a human also lives faster and dies younger

This research builds upon earlier studies of biological rhythms manifest as incremental growth lines in tooth enamel and skeletal bone tissue that were pioneered by Professor Alan Boyde, now of Queen Mary University of London's Institute of Dentistry. We hypothesised that these rhythms originate in the hypothalamus, a region of the brain that functions as the main control center for the autonomic nervous system and affect bone and body size and many metabolic processes, including heart and respiration rates. In fact, the rhythm is suggested by us to affect an organism’s overall pace of life and its lifespan. So, a rat that grows teeth and bone in a fraction of the time of a human also lives faster and dies younger according to a study our team first published in the February 2009 issue of Calcified Tissue International².

Philosophers have long sought to explain what governs the uniqueness of our complex set of behaviours that have developed in parallel with our extended life history and enlarged brains. For instance, Greek philosophers and alchemists (e.g., Zosimos of Panopolis) searched for a causal explanation of our longevity and sought to achieve it by drinking the “elixir of life”. We believe the properties that place humans and their complex minds into the world around us must be connected at some level to the complexity inherent in other life forms. Life scientists have for 70 years also queried the mechanism(s) that possibly explain how primate life is structured, but with no success. A solution to this inquiry is needed for understanding how human and non-human primate life history evolved and why it varies, enriching our potential for the good that such knowledge can bring for understanding ourselves. For instance, how and why do we achieve our characteristic adult body and brain sizes? How is body size variability in humans programmed? And does this program relate to other life history characteristics such as age at maturity and lifespan?

[caption id="attachment_53106" align="alignnone" width="620"] How do you calculate the factors involved directly in growth?[/caption]

To answer these questions we pursued evidence of a newly identified biological rhythm using analytical technologies not previously accessible to life scientists. Our research will bear specifically upon human and non-human primate biology, empowering physiologists, endocrinologists, ecologists and life historians with knowledge of a fundamental rhythm defining life structure. The aim of our team is to demonstrate the existence of a far reaching biological rhythm that holds the potential to explain the diverse nature of primate life history. Life history is a complex set of characteristics (length of gestation, lactation, age at sexual maturity and first breeding, lifespan, and interbirth interval) that curiously relate to our brain and body size and that define species, linking their respective growth strategies to various biological and ecological factors. Intriguingly, in comparative cross sectional primate research, these characteristics all scale positively and linearly with a "many-days", or, multidien, growth rhythm identified in dental enamel.

We reasoned the huge diversity in growth strategies of mammals must reside in higher order multidien biological timing that regulates growth timing and that enables life to diversify, conferring upon humans their characteristics that differ significantly from other species. Our team is overly curious by the prospect of finding an explanation to this inquiry, and we believe that seminal steps toward solving this are at hand. Our project team discovered the mammalian long period multidien metabolic rhythm in enamel (and bone) and elaborated a theoretical framework on which to forge a path of work. We then demonstrated a five-day rhythm in blood serum metabolites from domestic pigs over a two-week period; the same as their enamel rhythm. We accomplished this through partnering with the largest mass-spectrometry lab in the world. Our innovative metabolomics analysis revealed key biological functions linked to this rhythm: cell proliferation, apoptosis, and the concentration of calcium. These pathways provide a strong stepping stone to tease apart the interplay of these functions as key underlying mechanisms determining life history patterning. Our achievements already show that we are in a unique position to carry out and interpret data from other mammals and thus we are confident that the first experimental confirmation of the multidien rhythm in a primate will be successful.

The aim of our team is to demonstrate the existence of a far reaching biological rhythm that holds the potential to explain the diverse nature of primate life history

[caption id="attachment_53105" align="alignnone" width="367"] The research will hope to uncover more about multidien biological timing mechanisms.[/caption]

The community of researchers studying biological rhythms has missed the presence of long period multidien biological timing mechanisms because they employ small rodents as experimental animals, which regulate development and life history using only their daily biological clock. But chronobiology will experience a renaissance, as we think many biological and behavioural phenomena are apt to oscillate on a long period. For instance, a near-weekly period in heart rate and blood pressure in humans is hypothesised to correlate with their multidien rhythm, which averages eight or nine days. Stroke and heart attack occur during specific times of day, but there is also likely a near-weekly risk to which people are presently completely unaware. Further, when comparing human physical and cognitive development against known multidien rhythms, we expect to come into focus, for the first time, relationships to human growth and behaviour that have until now been overlooked.

Our work will have a potent impact by providing explanations for how differences in multidien biological timing account for variability in body size and life history. We anticipate that our research will have an immediate impact on the highly integrative field of metabolic ecology by showing how species’ body size and life history evolve in complete functional relation to their environment. As James H. Brown of the University of New Mexico explains: “Metabolism provides a basis for using first principles of physics, chemistry, and biology to link the biology of individual organisms to the ecology of populations, communities, and ecosystems.” Our work on multidien metabolic rhythms will provide the first detailed molecular insight into the biological mechanisms governing how species acquire and differ in their size and life history attributes.

We anticipate that our research will have an immediate impact on the highly integrative field of metabolic ecology by showing how species’ body size and life history evolve in complete functional relation to their environment

All of our experience tells us that the questions we ask will take us on a journey that will provide many fields with new questions and phenomenally interesting unknowns to chase. In biology, life history is among the most integrative of disciplines, and a study of long period multidien rhythms will be key to understanding the evolution of primates generally and humans specifically. For anthropology and palaeontology, we expect to better understand how human body size variation has arisen. In medicine and behaviour, the potential exists, respectively, for therapeutic intervention and performance optimisation.

Authors: 

Dr Timothy G. Bromage of the Department of Biomaterials & Biomimetics at NYU College of Dentistry

Dr Friedemann Schrenk, head of the Palaeoanthropology Division at the Senckenberg Research Institute and professor of Paleobiology at the Institute for Ecology, Evolution, and Diversity at Goethe University, both in Frankfurt

References:

1. http://dx.plos.org/10.1371/journal.pone.0145919 2. http://link.springer.com/article/10.1007%2Fs00223-009-9221-2

Acknowledgements

 

The team performing the study in PLOS ONE includes Dr. Youssef Idaghdour of the Department of Biology at NYU Abu Dhabi; Dr. Rodrigo S. Lacruz of the Department of Basic Science & Craniofacial Biology at NYU College of Dentistry; Dr. Thomas D. Crenshaw of the Department of Animal Science at the University of Wisconsin at Madison; Dr. Olexandra Ovsiy of the Department of Biomaterials & Biomimetics at NYU College of Dentistry; Dr. Björn Rotter and Dr. Klaus Hoffmeier, both of GenXPro GmbH in Frankfurt, Germany. The study was hosted by the Senckenberg Research Institute, Frankfurt, and funded by the 2010 Max Planck Research Award to TGB, administered by the Max Planck Society and the Alexander von Humboldt Foundation in respect of the Hard Tissue Research Program in Human Paleobiomics.