Molecular Biologists Identified Two Paths of Aging
Mon, April 19, 2021

Molecular Biologists Identified Two Paths of Aging


Understanding which cellular programs responsible for aging and how their dysregulation directs biological aging (senescence) is important to achieve lifespan extension in humans. Based on the cellular theory of aging, the human lifespan is determined by the aging of our cells. To determine whether different cells age by the same cause and at the same rate, a team of bioengineers and molecular biologists at the University of California San Diego has recently studied aging and found new insights on promoting “healthspan” – a period of one’s life that one is healthy.

Yeast as a model organism for studying cellular processes

The authors studied cellular aging using Saccharomyces cerevisiae, a species of yeast that’s been instrumental in baking and winemaking. Many essential cellular processes in yeast are the same in humans the reason why budding yeast has long been a popular model organism for biological research. It is easy to manipulate in the laboratory and can cope with different environmental conditions in the same way as human cells. The University of California San Diego researchers themselves consider it a tractable model for studying the mechanisms of aging, including the aging paths of stem and skin cells.

Mitochondrial decline and chromatin instability

The authors found that cells within the same environment and of the same genetic material can age in distinct ways. Using computer modeling, microfluidics, and other techniques, Yang Li from the Division of Biological Sciences and team discovered that about half of the yeast cells age due to dysfunction of their mitochondria, which generates most of the chemical energy needed to power cell’s biochemical reactions. The other half of yeast cells age through a “gradual decline in the stability of the nucleolus,” which is the largest structure in the nucleus of eukaryotic cells.

Their study, which appeared in the academic journal ScienceMag, explains that following the fate of yeast cells, aging is more of a programmable decision process instead of a simple accumulation of deleterious events. The cells embark on either the mitochondrial or nucleolar path early in life and follow the aging route throughout the lifespan. At the center of the controls, Li and the team found that there is a master circuit that guides the aging processes of cells.

Senior author Nan Hao, who is also an associate professor in the Section of Molecular Biology in the Division of Biological Sciences, told UC San Diego News Center that their team identified the molecular processes that underly each aging route as well as the connections among them to be able to understand how cells make said decisions.



Optimizing aging process

Hao and co-authors said that by creating a new model of aging, they could optimize and manipulate the aging process. Through computer simulations, they were able to reprogram the master aging circuit and modified their DNA. This then enabled them to genetically create a new aging route that promotes prolonged life.

Hao said that their findings raise the possibility of designing chemical-based therapies or a gene that will reprogram how human cells age intending to effectively extend human healthspan and delay human aging. The team went on to say that they will now test their new model in more complex organisms and cells and finally in human cells to find similar aging routes. Moreover, they plan to assess how combinations of drug “cocktails” and therapeutics may guide the pathways to longevity as well as to test the chemical techniques.

Co-author Lorraine Pillus from UCSD Moores Cancer Center states that much of the work highlighted in their paper is owed to having a strong interdisciplinary team that they assembled. One great aspect of their group, for instance, is that they conduct experimentation to find out if the model is correct or not and they also do the modeling themselves. These repetitive processes are important for their work.

Other researchers include Yanfei Jiang, Jeff Hasty, Richard O’Laughlin, Lev Tsimring, Yuelian Zhu, Stephen Klepin, and Julie Paxman. The National Science Foundation Molecular and Cellular Biosciences and the National Institutes of Health supported the study.

The aging population: statistics

The United Nations estimates that older persons are expected to outnumber children under 10, which is 1.41 billion older persons vs. 1.35 children, in 2030. It states that the populating aging, defined as the inevitable increase in the share of older persons that results from improvement in survival and decline infertility, is happening throughout the world.

In its 2017 World Population Prospects report, the UN said that every country in the world will experience a substantial increase in the size of the population aged 60 years or over. In Africa alone, there were 68.7 million persons aged 60 years or over and it will grow to 225.8 million in 2050. In Asia, the number will also increase from 549.2 million to 1.2 billion. In Europe, from 183 million in 2017, the number of aging persons will grow to 247.2 million in 2050.



Of the 103 middle-income countries with at least 90,000 inhabitants, 78% of them are expected to see the number of older people increase more than twofold. The top countries with the largest share of persons aged 60 years or over in 2017 were Japan (33.4%), Italy (29.4%), Germany (28%), Portugal (27.9%), Finland (27.8%), Bulgaria (27.7%), Croatia (26.8%), Greece (26.5%), Slovenia (26.3%), and Latvia (26.2%).

By 2050, Japan will remain as the top country with the largest share of persons aged 60 years or over followed by Spain (41.9%), Portugal (41.7%), Greece (41.6%), and Republic of Korea (41.6%).

Meanwhile, database company Statista shares that in South Korea, Gyeonggi province holds the most (1.5 million) population aged 65 years and above in 2019. There was also approximately 1.4 million elderly in Seoul, 591,000 in Busan, 527,000 in Gyeongbuk, 524,000 in Gyeongnam, and 396,000 in Jeonnam.

Aging process may not be a pleasant experience for all but just because one is older doesn’t mean they have to look or feel it. They can practice habits that slow down aging, such as managing stress, thinking positively, being social, sleeping well, taking vitamin B, drinking enough water, keeping the brain active, and eating healthy foods. The findings of the University of California San Diego scientists also promise a new way to promote healthspan.