Various age-related disorders accumulate during aging, causing a decline in tissue and organ function, raising the risk of disease development, and leading to death. Age-related phenotypes are tightly related to an increase in coordinated, progressive changes in the transcriptome, proteome, metabolome, microbiome, and epigenome. Age-dependent modifications of the transcriptome, caused by changes in epigenetic, transcriptional, and post-transcriptional regulation of gene expression, lead to the accumulation of age-related changes in the proteome and metabolome. In turn, dynamic changes in the microbiota during aging also affect gene expression and thus lead to age-related changes in the proteome and metabolome. Recent studies have shown that multi-omic rejuvenation technologies decrease age-related disorders and extend longevity. For example, the short-term induction of the expression of transcription factors that ensure the reprogramming of somatic cells into pluripotent stem cells is accompanied by the restoration of the DNA methylation pattern and transcriptome expression profile characteristic of younger tissues, resulting in an increased lifespan. In this review, we discuss existing multi-omic rejuvenation technologies and the prospects for extending and improving life.