Life expectancy has doubled in the last 150 years and with it has come the proverbial “silver tsunami” – a cost to society for increasing lifespan with a concomitant rise in chronic disease incidence. Geroscience is essentially an interdisciplinary field at the crossroads of aging and age-related diseases.
Given this dramatic increase and that age is the greatest risk factor for a majority of chronic diseases driving both morbidity and mortality, the National Institutes of Health’s Geroscience Interest Group (GSIG) – an interdisciplinary band of researchers – is calling for more collaboration, both within the NIH and with its funded external researchers.
They say it is critical to expand geroscience research directed at extending human healthspan, pointing out that 46 percent of Medicare spending is for people with six or more chronic conditions, including diabetes and heart disease.
Clearly, living longer doesn’t always mean living better. “Healthspan,” the length of a lifetime that is spent in optimal health, is the lynchpin for better aging. Age itself is the predominant risk factor for most diseases and conditions that limit healthspan. This knowledge launched the idea of geroscience, which strives to understand how aging enables chronic disease and seeks to develop novel multi-disease preventative and therapeutic approaches.
In a commentary published in Cell earlier this month, the GSIG outlined a strategy to develop these approaches. They call for geroscience to merge with ongoing research on human chronic disease states, compare and contrast inflammation in aging and disease, and develop new animal models of aging, among other recommendations.
Shelley Berger, PhD, a professor of Cell and Developmental Biology and director of the Penn Epigenetics Program, is part of the GSIG. She is using unique model organisms, such as eusocial ants, to study the epigenetic control of aging. Epigenetics is the idea that changes in gene expression and characteristics can occur without mutations in DNA, instead by chemical modifications to DNA and its supporting and organizing proteins.
Berger observes that all of the genes known to be major epigenetic regulators in mammals are conserved in ants, which makes them a “fantastic model for studying behavior and longevity. They provide an extraordinary opportunity to explore and understand the epigenetic processes that underlie many human diseases and the aging process.”
To understand how behavioral and physiological differences, such as lifespan, in ant castes arise, the team is investigating how the chemical modifications of the support proteins (called histones) around which the DNA strands are wrapped can activate or turn genes off. Her team’s hypothesis is that these chemical modifications to histones change with age in ants to control such behaviors as foraging, defense, and care for young. Her lab is now studying whether they can manipulate this system in ants, using compounds that alter the epigenetic modifications, to hasten the age of onset at which the ants leave the nest to forage, using the Florida carpenter ant as a model.
Berger and other researchers studying epigenetics say that the lack of validated biomarkers of human aging has impeded progress in solving the mysteries of the molecular underpinnings of aging. They argue that epigenetic changes present promising biomarkers, and, if validated, could be used to examine deterioration associated with abnormal aging, and ultimately, to test interventions to bolster normal aging.
But, it remains unclear whether these markers forecast chronologic or biologic age, which are likely distinct. That is, there may be changes to the epigenetic modification that always occur with the aging clock, whether or not abnormal deterioration to cells occur. If the status of the chemical modifications to the epigenome does indeed indicate biologic age – normal healthy aging compared to abnormal – then a major hurdle to initiating human studies will be overcome because status of the epigenetic modification will indicate the age-related deterioration state.
Also, if similar modifications are identified in mice, they could then be validated by determining whether chronic stressors, such as alcohol, accelerate the abnormal epigenetic changes, and importantly, whether interventions such as epigenetic pharmacological drugs could delay the negative changes.
“The epigenetic landscape could reveal and explain the relationship between aging and the increase in chronic diseases that manifest throughout the body, such as inflammatory problems, because epigenetic mechanisms occur throughout all cells in the body,” says Berger. “This, we hope, may one day lead to finding epigenetic therapeutics to hold back the aging epigenome and delay the onset of multiple, co-occurring chronic diseases.”