Some new insights in aging with comparative views of animal and plant agingAlmost all living organisms undergo aging and death process along age. Why and how organisms age and die? Here, I present some of the insights I learned from my studies of aging in plants and animals.
1) Evolution of life span in rice.
We investigated the genetic factors responsible for the differential senescence patterns and lifespans between indica and japonica-type rice cultivars. We found that 8 bp insertion in the promoter region of indica variety led to higher and earlier induction of OsSGR, the chlorophyll-degrading enzyme Mg++ dechelatase, which resulted in accelerated senescence and shorter lifespans. Evolutionary analyses show the indica-type promoter was acquired from the progenitor subspecies O. nivara during its evolution. The result showed, for the first time, a case of a facile evolution of life span through evolution of a promoter sequence.
2) Oscillatory code of aging.
The circadian clock in organisms has evolved to enable adaptation to periodic environmental changes, generating an internal rhythm of gene expression within a ~24 h period. We previously reported that aging leads to shortened circadian period with 20 ~ 22 h period in Arabidopsis. Here, I present the data that aged Arabidopsis leaves survive better in an artificial light/dark cycle of 20 h than that of 24 h through resonance between the internal circadian period and the external light cycle. We consider this circadian resonance-mediated control of senescence as an “oscillatory code of plant aging and senescence”.
I have also tested the age-dependent change of circadian rhythm in killifish, an animal aging model system with the shortest lifespan in vertebrates and found that the circadian rhythm is weakened with deterioration of circadian system.
3) Prediction of remaining life span.
In plants, we found that the circadian rhythmic gene expression pattern undergoes age-dependent warping and the remaining life span of plant leaves can be predicted by measuring the present warping degree of circadian rhythm.
In C. elegans, an animal model system of aging, we found that the remaining life span can be predicted by measuring the maximum velocity of movement.
4) Loss of regenerative capacity.
Loss of regenerative capacity is commonly observed in animal and plants.
In plants, de novo root regeneration for cut leaves is associated with an ultradian gene expression rhythm with 3 hr period and aging lead to loss of root regeneration and the ultradian rhythm.
5) miRNAs in control of aging.
In Arabidopsis, miR164 is upregulated during plant aging and functions as a negative regulator of aging, forming time-evolving networks. In mouse brain, miR204 is age-upregulated in hypothalamus but functions as a positive regulator of brain aging. Inhibition of miR204 expression in Alzheimer’s disease model mouse leads to partial rescue of brain functions.
6) Rejuvenation of aged pancreatic islets.
Rejuvenation of old trees is facilely achieved by micrografting to young plants. We found, when transplanted into the anterior chamber of the eye of young mice with diabetes, pancreatic islets from old mice were rejuvenated, showed strong islet cell proliferation, and fully restored control of glycemia.
7) Some new endeavors in the Ever Summer Labs for Aging Research.
Since I moved to the new institute, Ever Summer Institute for Aging Research, I am setting up a screening system to find aging- and lifespan altering materials based on killifish, the shortest living vertebrate aging model. The effort will include repositioning of known drugs and natural compounds.
I am also attempting gene therapy of aging, for example, to introduce a centenarian genome sequence into normal human cells using a brand new gene editing system I developed.
講者: Dr. Hong Gil Nam (Director, Ever Summer Labs for Aging Research, Daegu Catholic University, Korea)
主持人: Dr. Yet-Ran Chen
時間:2023/07/10 11:00 AM