A wide range of human diseases, including cancer, has a striking age-dependent onset. However, the molecular mechanisms that connect aging and cancer are just beginning to be unraveled. FOXO transcription factors are promising candidates to serve as molecular links between longevity and tumor suppression. These factors are major substrates of the protein kinase Akt. In the presence of insulin and growth factors, FOXO proteins are relocalized from the nucleus to the cytoplasm and degraded via the ubiquitin-proteasome pathway.
Proceedings of the National Academy of Sciences of the United States of America
The burden of protein misfolding is believed to contribute to aging. However, the links between adaptations to conditions associated with protein misfolding and resistance to the time-dependent attrition of cellular function remain poorly understood. We report that worms lacking aip-1, a homologue of mammalian AIRAP (arsenic-inducible proteasomal 19S regulatory particle-associated protein), are not only impaired in their ability to resist exposure to arsenite but also exhibit shortened lifespan and hypersensitivity to misfolding-prone proteins under normal laboratory conditions.
To live beyond the octogenarian years, population and molecular genetic studies of centenarian sibships indicate that genetic factors play an increasingly important role as the limit of life span is approached. These factors are likely to influence basic mechanisms of aging that in turn broadly influence susceptibility to age-related illnesses. Lacking genetic variations that predispose to disease as well as having variations that confer disease resistance (longevity enabling genes) are probably both important to achieving exceptional old age.
MicroRNAs, a class of small, non-coding RNAs, are now widely known for their importance in many aspects of biology. These small regulatory RNAs have critical functions in diverse biological events, including development and disease. Recent findings show that microRNAs are essential for lifespan determination in the model organisms, Caenorhabditis elegans and Drosophila, suggesting that microRNAs are also involved in the complex process of ageing.
Ageing in diverse species ranging from yeast to humans is associated with the gradual, lifelong accumulation of molecular and cellular damage. Autophagy, a conserved lysosomal, self-destructive process involved in protein and organelle degradation, plays an essential role in both cellular and whole-animal homeostasis. Accumulating evidence now indicates that autophagic degradation declines with age and this gradual reduction of autophagy might have a causative role in the functional deterioration of biological systems during ageing.
When growing on solid surfaces, yeast, like other microorganisms, develops organized multicellular populations (colonies and biofilms) that are composed of differentiated cells with specialized functions. Life within these populations is a prevalent form of microbial existence in natural settings that provides the cells with capabilities to effectively defend against environmental attacks as well as efficiently adapt and survive long periods of starvation and other stresses.
Life's timekeeper is a 'free-running' intracellular oscillator synchronised across all cells. It runs throughout life splitting lifespan into equal length phases. During the maturational period it controls the overall rate of progression whereas in the post-maturational period it controls the overall rate of ageing. This includes the rate of senescence and hence time to death. As such life's timekeeper equates maturational and post-maturational time, hence explains the tight correlation between these time periods that has existed throughout mammalian evolution.