Learning to grow old gracefully: the inevitability of ageing

Ageing, or senescence, was considered an inescapable fate of living organisms in the past, where stories of immortality remained in the realm of science fiction. However, in recent years, scientists have developed compelling theories to propose a genetic basis to ageing, implying a means to either avoid or delay the process. Nonetheless, new scientific evidence shows that ageing is, in fact, inevitable!

Consider natural selection, a concept where individuals that are ‘fitter’ are more likely to reproduce. With more offspring, the genes that are responsible for ‘fitness’ are selected and amplified over time. However, there is a shortfall in this selecting mechanism – genes that promote fitness in youth, but simultaneously have damaging effects at a later stage in life. In other words, Mother Nature stops selecting when the organism starts to produce offspring. This ‘selection shadow’ for organisms that pass their reproductive age permits genes that contribute to late-stage deleterious effects to be passed on. These genes are termed ‘longevity genes’ and it was believed that, by manipulating these genes, slowing ageing was no longer an impossible task.

“It was previously believed that by manipulating longevity genes slowing ageing was possible”

To understand these longevity genes, scientists have studied ageing in various organisms at a cellular level. It was postulated that ‘garbage’, like misfolded proteins, needs to be removed from a cell for normal function. Failure to do so results in cell malfunctioning and senescence. This is particularly enhanced in single-celled organisms, where there is intercellular competition between somatic cells: the more efficient the cell-garbage removal processes are, the longer the cell lives.

“It was postulated that ‘garbage’, like misfolded proteins, needed to be removed from a cell for normal function”

Comparably, in a multicellular organism, similar to you and I, intercellular competition is also occurring. Since we need our cells to work with each other to serve a larger function (e.g. muscle cells work together to form a muscle tissue, which can contract and allow movement), removal of non-cooperative cells is an important task to maintain the organism’s fitness. Thus, it is imperative to weed out non-functioning cells that do not work well together. Additionally, intercellular competition is constantly occurring, where cells which are unable to grow as well as their counterparts are eliminated, whilst highly functioning cells, with higher proliferative rate, are selected.

However, intercellular competition is a two-edged blade. Although senesced cells are generally slow in growth, warranting their removal, cells with high proliferative capacity serving no particular function are still allowed to grow. Consider cancer cells that out-compete other cells in the region despite having zero benefits to the host organism. To eliminate cancer, the extent of intercellular competition must be reduced, and this eventually leads to the decline in cellular cooperation and the subsequent ageing process.

“By studying fruit flies and worms, evidence suggested that ageing is an inevitable part of living”

By studying fruit flies and worms, evidence that supports this notion was shown, where intercellular competition prevents accumulation of ageing cells at the expense of cancerous cell growth. Vice versa, a delay of intercellular competition causes a loss of functional cells, therefore cells don’t cooperate as well as before. This evidence suggests that ageing is an inevitable part of living.

Nevertheless, this topic is under ongoing investigation. By studying and comparing the degree of intercellular competition in different species, the process of ageing could be understood better, and perhaps, in the future, be delayed!

DOI: 10.1073/pnas.1618854114